United States Patent 9,079,934 Landscape: Scope and Claim-Chart-Level Analysis for Exon-53 Dystrophin-Skipping Antisense Oligomers (SEQ ID NO: 35; Morpholino and Modified Backbone Claims)
Executive summary
- US 9,079,934 is a composition-of-matter patent focused on antisense oligomers that induce skipping of exon 53 in the human dystrophin (DMD) gene, with primary claim coverage tied to one specific sequence: SEQ ID NO: 35, plus backbone/sugar/phosphate-region modification fallbacks (including morpholinos and sulfur/phosphorus analog backbones).
- The independent claim is narrow on sequence (must be SEQ ID NO: 35) but broad on chemistry (covers any oligonucleotide format that includes specific sugar and/or phosphate-binding modifications, and includes morpholino embodiments).
- The dependent claims pull coverage into: morpholino oligomers, ribose 2’-substituted analogs, phosphorothioate/phosphorodithioate/alkylphosphonate/phosphoramidate/boranophosphate linkages, phosphorodiamidate morpholinos, and a defined 5’ end morpholino chemistry (chemical formulae (1) to (3) not reproduced in the prompt).
- Patent landscape risk for competitors/generics largely depends on whether their exon-53 agents use the exact SEQ ID NO: 35 sequence and/or infringe under the asserted modification language (sugar/phosphate-binding “at least one nucleotide” modified).
What exactly does US 9,079,934 claim for exon 53 dystrophin skipping?
Short answer: It claims an antisense oligomer defined by sequence SEQ ID NO: 35 that causes skipping of the 53rd exon in human dystrophin, with permitted coverage for modified sugar and/or phosphate-binding regions, including morpholino oligomers.
Independent claim 1 scope: sequence lock + chemistry flexibility
Claim 1 elements (must all be met):
- Function: “causes skipping of the 53rd exon in the human dystrophin gene.”
- Sequence: “consisting of the nucleotide sequence of SEQ ID NO: 35.”
- Molecular format: an antisense oligomer that is an:
- oligonucleotide with sugar moiety and/or phosphate-binding region modified in at least one nucleotide, or
- a morpholino oligomer.
Interpretation for infringement / freedom-to-operate (FTO):
- The “consisting of” language around SEQ ID NO: 35 is a strong sequence boundary. If a candidate uses a different exon-skipping sequence, claim 1 does not read even if it also induces exon 53 skipping.
- The claim then expands breadth across backbone chemistries:
- It is not limited to unmodified phosphodiester DNA/RNA.
- It captures oligonucleotides where at least one nucleotide has modified sugar moiety and/or phosphate-binding region.
- It explicitly includes morpholino (which replaces the backbone with a morpholine ring and non-ionic phosphorodiamidate linkage).
Dependent claim 2: forces morpholino in
Claim 2 depends from claim 1:
- “wherein the antisense oligomer is a morpholino oligomer.”
This collapses non-morpholino formats under claim 2. In practice, claim 2 gives a cleaner enforcement path against morpholino exon-skipping molecules using SEQ ID NO: 35.
Dependent claim 3: 2’-OH replaced with enumerated substituents
Claim 3 depends from claim 1:
- “sugar moiety … is a ribose in which the 2’-OH group is replaced by any one selected from [OR, R, R′OR, SH, SR, NH2, NHR, NR2, N3, CN, F, Cl, Br, I].”
Meaning:
- This is a 2’-substitution claim family typical of antisense chemistries (2’-O-alkyl/2’-O-aryl/2’-O-(alkylene) variants; halogens; amino/thiol/cyano/azido).
- It remains sequence-anchored to SEQ ID NO: 35 and still requires exon-53 skipping.
Enforcement lever:
- For candidates using SEQ ID NO: 35 with 2’-substituted ribose (not morpholino), claim 3 is a narrower but potentially easier-to-prove subset.
Dependent claim 4: phosphate-binding region enumerated linkages
Claim 4 depends from claim 1:
- “phosphate-binding region … is any one selected from: phosphorothioate bond, phosphorodithioate bond, alkylphosphonate bond, phosphoramidate bond, boranophosphate bond.”
Meaning:
- Covers multiple modified phosphate linkages beyond canonical phosphodiesters.
- Again, sequence anchored to SEQ ID NO: 35 and functional exon-53 skipping required.
Dependent claim 5: phosphorodiamidate morpholino
Claim 5 depends from claim 2:
- “morpholino oligomer is a phosphorodiamidate morpholino oligomer.”
Meaning:
- This is essentially the classic morpholino linkage (non-ionic phosphorodiamidate).
- If a morpholino competitor uses phosphorodiamidate morpholino and SEQ ID NO: 35, claim 5 tightens enforcement.
Dependent claim 6: morpholino 5’ end chemical formulas (1) to (3)
The prompt provides the legal dependency but not the content of chemical formulae (1) to (3). The scope hinges on what those formulas cover:
- This claim is a further narrowed morpholino embodiment limited by the 5’ terminus chemistry.
Dependent claim 7: composition for muscular dystrophy
Claim 7 depends from claim 1:
- A “pharmaceutical composition for the treatment of muscular dystrophy” comprising:
- the antisense oligomer of claim 1, or a salt or hydrate.
Meaning:
- Claim 7 covers formulation-level compositions, but the active ingredient is defined by the claim 1 oligomer (again, SEQ ID NO: 35 and functional exon-53 skipping).
- This can matter for licensing or product-formulation disputes if the platform uses identical active oligo but different salts/hydrates.
How do the claim terms narrow or broaden US 9,079,934 coverage?
Sequence requirement: “consisting of the nucleotide sequence of SEQ ID NO: 35”
- The “consisting of” phrasing generally indicates that the oligonucleotide’s identity is defined by that sequence; it is not simply “having complementarity to exon 53.”
- For design-around, the most straightforward path is:
- use a different antisense sequence (different SEQ ID number), even if it produces exon-53 skipping.
Function requirement: “causes skipping of the 53rd exon”
- This is both:
- a required property for validity/infringement, and
- a potential proof battleground (cell-based splicing assays, exon skipping readouts).
Chemistry flexibility via “modified” sugar/phosphate language
- Claim 1 covers oligonucleotides with sugar moiety and/or phosphate-binding region modified in at least one nucleotide.
- Dependent claims 3 and 4 provide specific enumerations, meaning claim 1 may cover even additional modifications, but enforcement typically benefits from the enumerated subsets in dependent claims.
Morpholino carve-in
- Claim 1 includes morpholino oligomers as an explicit category.
- Claims 2 and 5 then constrain morpholino to phosphorodiamidate morpholino.
What do the enumerated sugar and phosphate modifications cover commercially and technically?
2’-substitutions in claim 3
Coverage includes:
- 2’-O-alkyl/aryl patterns (OR, R, R′OR)
- 2’-thio variants (SH, SR)
- 2’-amino variants (NH2, NHR, NR2)
- 2’-azido (N3)
- 2’-cyano (CN)
- 2’-halogens (F, Cl, Br, I)
This is a broad sweep consistent with common antisense modalities (2’-OMe, 2’-MOE-like variants, 2’-F, 2’-Cl, etc.). The exact breadth against any given product depends on whether the product uses ribose and the exact 2’-substitution listed.
Phosphate linkages in claim 4
Coverage includes multiple backbones:
- phosphorothioate (P=S)
- phosphorodithioate (two sulfur substitutions)
- alkylphosphonate
- phosphoramidate
- boranophosphate
These map onto many “stabilized” antisense backbones designed to improve nuclease resistance and PK.
Morpholino backbone in claim 5
- “phosphorodiamidate morpholino” is consistent with typical morpholino exon-skipping drugs.
- The morpholino format typically avoids some of the RNA-like sugar constraints; claim 3 would not apply if the molecule is not a ribose-based oligonucleotide, but claim 2/5 do.
What product candidates are at risk: how to evaluate infringement under US 9,079,934?
Featured-snippet answer: Risk concentrates on products that use SEQ ID NO: 35 (exact sequence) to induce DMD exon 53 skipping, especially those using morpholino or enumerated 2’-substituted ribose / phosphate-modified oligos.
Infringement checklist by claim
- Claim 1:
- Sequence = SEQ ID NO: 35
- Molecule type = modified oligonucleotide (sugar and/or phosphate modifications) OR morpholino
- Activity = causes exon 53 skipping
- Claim 2/5:
- Morpholino format + phosphorodiamidate + SEQ ID NO: 35 + exon 53 skipping
- Claim 3/4:
- Ribose 2’-substitution in enumerated list OR specific phosphate linkages in enumerated list + SEQ ID NO: 35 + exon 53 skipping
- Claim 7:
- Product formulation that contains the claim 1 active as active ingredient (salt/hydrate permitted)
Design-around routes (sequence-level)
- Replace SEQ ID NO: 35 with a different sequence that still yields exon 53 skipping. That is the cleanest avoidance because the claims are “consisting of” a particular sequence.
Design-around routes (chemistry-level)
- For morpholino candidates: switching away from phosphorodiamidate morpholino might avoid claim 5, but claim 2 could still read if the product remains a morpholino and still uses SEQ ID NO: 35.
- For ribose-based candidates: using a sugar backbone not covered by claim 3 and a phosphate linkage not covered by claim 4 can reduce dependent-claim reach, but claim 1 may still cover other modifications due to its broader “sugar moiety and/or phosphate-binding region … modified” language.
How broad is the patent estate around exon 53 dystrophin skipping compared with neighboring exon programs?
Answer framing: US 9,079,934 is sequence-defined, which differs from many exon-skipping patent families that are drafted around “exon 45-55” or “targeting exon X” with ranges and degeneracy. Sequence locking makes this patent behave more like a specific oligo patent than a generic exon-targeting platform patent.
Expected landscape pattern (based on typical DMD exon-skipping portfolios)
In DMD antisense, portfolios often split across:
- sequence-specific claims for individual antisense oligos,
- backbone chemistry claims (2’-modifications, phosphate linkages, morpholino variants),
- formulation claims,
- use claims (method-of-treatment).
US 9,079,934 clearly sits in the first cluster (sequence) plus chemistry and composition.
Where other patents commonly overlap
Even when a specific sequence patent exists, competitors often attempt to:
- license backbone-chemistry patents,
- adopt alternative sequences,
- rely on later-expiring combination/product patents.
This patent’s impact depends on whether other related patents cover the same active sequence SEQ ID NO: 35 across different claim formats (manufacturing, intermediates, delivery conjugates, dosing regimens). Those are not provided in the prompt.
Orange Book, FDA, and exclusivity: what is protected beyond the patent?
No Orange Book listing analysis can be produced from the prompt alone because antisense exon-skipping drugs are not typically evaluated through the Orange Book in a way that maps cleanly to a single US composition-of-matter patent number without the underlying marketed NDA/BLA, listed active ingredient, and Orange Book patent reference set.
Therefore: a complete, accurate “Orange Book status of US 9,079,934” cannot be generated from the provided information.
How strong is the patent claim set in litigation terms?
Strengths
- Sequence anchoring (SEQ ID NO: 35) gives clear claim boundaries for infringement analysis.
- Functional requirement still reduces the risk that unrelated molecules are swept in, but it can increase the evidentiary burden.
- Dependent claims provide multiple fallback chemical embodiments, particularly:
- morpholino (claim 2 and 5),
- enumerated 2’-substitutions (claim 3),
- enumerated phosphate linkages (claim 4).
Vulnerabilities
- Any validity challenge targeting the specificity of SEQ ID NO: 35 and the basis for claiming exon-53 skipping would focus on:
- whether the sequence and exon-skipping effect were disclosed earlier,
- whether “causes skipping” is adequately supported across the claim’s breadth (especially for multiple backbone modifications).
- If the prior art includes the same or substantially identical antisense sequences, novelty and non-obviousness become central.
Patent expiration timeline and exclusivity: what does the end-date look like?
A precise expiration timeline (including term adjustments, patent term extension, and potential exclusivity interactions) cannot be computed from the prompt. US 9,079,934’s filing date, issue date confirmation, and any PTA/PTE data are not provided.
Therefore: no expiration calendar should be asserted here.
Key Takeaways
- US 9,079,934 is a sequence-locked DMD exon-53 skipping antisense patent centered on SEQ ID NO: 35, with broad chemistry coverage through modified sugar and/or phosphate-binding regions and explicit inclusion of morpholino oligomers.
- The strongest enforcement lanes are:
- morpholino products using the same sequence (claims 2 and 5),
- ribose-based products using enumerated 2’-substitutions (claim 3),
- products using enumerated phosphate linkages (claim 4),
- product formulations containing the same active oligo (claim 7).
- Design-around risk is dominated by whether the competitor uses the exact SEQ ID NO: 35. Changing sequence is the most direct avoidance strategy; backbone changes may shift infringement from independent claim 1 to dependent claim limitations.
FAQs
1) Does US 9,079,934 cover any antisense that skips exon 53, or only SEQ ID NO: 35?
It is limited to antisense oligomers “consisting of” SEQ ID NO: 35 that cause exon 53 skipping.
2) Are morpholino exon-skipping versions automatically covered?
They are covered under claim 1 if they use SEQ ID NO: 35 and induce exon 53 skipping; claim 2 further limits to morpholino, and claim 5 to phosphorodiamidate morpholino.
3) If a competitor uses a different 2’-substituted ribose chemistry, is infringement avoided?
Not necessarily. Claim 1 covers oligonucleotides with modified sugar and/or phosphate-binding regions, while claims 3 and 4 provide specific enumerated fallbacks.
4) Can a generic or follow-on product avoid the patent by changing the formulation but using the same oligo?
Claim 7 covers pharmaceutical compositions containing the claim 1 antisense oligomer (or acceptable salts/hydrates). Formulation changes alone may not avoid infringement.
5) What evidence is typically required to prove “causes skipping of the 53rd exon”?
Exon-skipping is typically established by splicing assay data in relevant cells or models showing exon 53 skip as the pharmacodynamic effect tied to the claimed sequence.
References
(No citations were provided in the prompt; therefore no referenced sources can be listed.)
