Details for Patent: 9,670,492

Which drugs does patent 9,670,492 protect, and when does it expire?

Patent 9,670,492 protects DAWNZERA (AUTOINJECTOR) and is included in one NDA.

This patent has nineteen patent family members in thirteen countries.

Summary for Patent: 9,670,492

Title:	Modulation of prekallikrein (PKK) expression
Abstract:	Disclosed herein are antisense compounds and methods for decreasing PKK mRNA and protein expression. Such methods, compounds, and compositions are useful to treat, prevent, or ameliorate PKK-associated diseases, disorders, and conditions.
Inventor(s):	Susan M. Freier, Huynh-Hoa Bui
Assignee:	Ionis Pharmaceuticals Inc
Application Number:	US14/915,039
Patent Claim Types: see list of patent claims	Use; Composition;

Executive summary
U.S. Patent No. 9,670,492 claims a chemically modified, single-stranded oligonucleotide with a defined length (12–30 linked nucleosides) and a highly specific complementarity relationship to a target nucleobase segment in SEQ ID NO: 10 (including a hard minimum of at least 8 contiguous bases at 100% complementarity and ≥90% complementarity across the full oligonucleotide). The independent claim further narrows structure to a gap-gap “wing” architecture: a central gap of linked deoxynucleosides flanked by 5′ and 3′ wing segments of linked nucleosides whose sugars are modified. Dependent claims specify sugar chemistries (including bicyclic sugars and 2′-substituted nucleosides with 2′-OCH3, 2′-F, 2′-O-methoxyethyl), internucleoside linkage (phosphorothioate), nucleobase modifications (5-methylcytosine), and explicit sequence embodiments limited to SEQ ID NO: 570 (and a closed set of SEQ ID NOs in claim 18). The patent’s litigation and freedom-to-operate impact will depend on whether the challenger’s oligo uses this same gap-wing architecture, sugar modification class, and complementarity constraints to SEQ ID NO: 10’s positions 27427–27466.

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Patent 9,670,492 scope and claims: what oligonucleotide structures does it protect in the US?

What is the independent claim scope (Claim 1) for US 9,670,492?

Claim 1 protects a compound defined by a combination of sequence-recognition rules and structural chemistry rules.

Core sequence constraints

The modified oligonucleotide has:

• Length: 12–30 linked nucleosides
• Target complementarity:
  • Includes a nucleobase sequence that contains a portion of at least 8 contiguous nucleobases that is 100% complementary to an equal-length portion of nucleobases 27427–27466 of SEQ ID NO: 10
  • Across the entire oligonucleotide, the nucleobase sequence is at least 90% complementary to SEQ ID NO: 10 as measured over the entirety

This makes the claim more than generic “antisense complementarity.” It hard-sets a contiguously perfect seed-like block (≥8 bases) and a global identity/complementarity threshold (≥90% over the full length).

Structural constraints (required architecture)

Claim 1 also requires a specific chemical topology:

• Gap segment: “consisting of linked deoxynucleosides”
• 5′ wing segment: “consisting of linked nucleosides”
• 3′ wing segment: “consisting of linked nucleosides”
• Positioning: gap segment is between the 5′ wing and 3′ wing
• Wing sugar modification requirement: each nucleoside in each wing segment comprises a modified sugar
• The claim does not state that the gap nucleosides have modified sugars; it specifies the gap as linked deoxynucleosides, which typically implies 2′-deoxy.

Structural implication for infringement mapping

To fall within Claim 1, a candidate oligonucleotide must satisfy both:

1. The complementarity/math constraints relative to SEQ ID NO: 10 positions 27427–27466, and
2. The gap-wing with modified sugars in wings (gap of deoxy; wings of modified sugars).

A sequence that matches the recognition rules but lacks the gap-wing topology does not meet Claim 1. A gap-wing oligo with modified wing sugars but which misses the 8-base 100% complementary block (or fails ≥90% global complementarity) also does not meet Claim 1.

How do Claims 2–3 narrow the claim family to single-stranded nucleic acids and base modifications?

• Claim 2 requires the modified oligonucleotide is a single-stranded oligonucleotide.
• Claim 3 requires at least one nucleoside comprises a modified nucleobase.

Claim 3 is a structural overlay on top of Claim 1. Even if a compound matches all architecture and complementarity constraints, it exits the scope of Claims 3+ if nucleobases are unmodified.

Which nucleobase modifications are expressly claimed (Claim 4)?

• Claim 4 specifies the modified nucleobase is 5-methylcytosine.

This is significant: Claim 4 ties “modified nucleobase” to a specific chemistry. A competitor with a different nucleobase modification class would not satisfy Claim 4 (but could still potentially satisfy Claim 3 depending on how the modification is construed).

How do Claims 5–6 constrain internucleoside linkage chemistry?

• Claim 5: at least one internucleoside linkage is a modified internucleoside linkage.
• Claim 6: each internucleoside linkage is a phosphorothioate internucleoside linkage.

This is a high bar for infringement because Claim 6 requires all linkages to be phosphorothioate. A mixed linkage chemistry (e.g., phosphodiester blocks, 2′-O-methyl with non-PS linkages, or other backbone chemistries) could avoid Claim 6 while still falling within Claim 5 if “at least one” is modified.

What do Claims 7–10 say about uniform vs mixed sugar modifications and bicyclic sugars?

• Claim 7: each modified sugar has the same modification.
• Claim 8: at least one modified sugar has a different modification (mixed sugar types).
• Claim 9: at least one modified sugar is a bicyclic sugar.
• Claim 10: bicyclic sugar selected from cEt, LNA, and ENA.

Taken together, Claims 7–10 create multiple pathways into coverage:

• A product with a single bicyclic sugar class across the wings can satisfy Claim 9 + 10 and possibly Claim 7.
• A product mixing bicyclic classes can satisfy Claim 9 + 10 and Claim 8.

How do Claims 11–12 constrain 2′ sugar substituents?

• Claim 11: at least one nucleoside comprising a modified sugar is a 2′-substituted nucleoside.
• Claim 12: substituent at 2′ is selected from:
  • 2′-OCH3
  • 2′-F
  • 2′-O-methoxyethyl

These claims matter because many commercial antisense formats use 2′-O-methyl, 2′-F, or 2′-MOE. The patent’s requirement that these appear in nucleosides with modified sugars within the wing segments ties the sugar chemistry to the required topology.

How does Claim 13 constrain oligo length further?

• Claim 13: oligo consists of 16, 17, 18, 19, or 20 linked nucleosides.

This is a narrower length embodiment within Claim 1’s broader 12–30 range. A competitor outside these lengths can still theoretically infringe Claim 1 if it meets complementarity and topology, but not the narrower dependent coverage.

What is Claim 14’s sequence formula embodiment and what chemistry labels does it lock in?

Claim 14 recites a formula sequence using variables mapped as:

• A = adenine
• mC = 5-methylcytosine
• G = guanine
• T = thymine
• e = 2′-O-methoxyethyl modified nucleoside
• d = 2′-deoxynucleoside
• s = phosphorothioate internucleoside linkage

The claim recites a specific sequence string with these symbols (Tes Ges mCes ... etc.). Even without the full alignment shown in your excerpt, the presence of mC and e and d and s makes this dependent claim a chemically specific embodiment: it locks in

• base identity and modification (5-methylcytosine),
• wing sugar substitution via 2′-O-methoxyethyl,
• gap deoxynucleosides, and
• phosphorothioate backbone across internucleosides.

For infringement practice, Claim 14 is the most “engineering-ready” claim: it reads like a blueprint for an exact drug substance sequence + chemical substitution pattern.

What do Claims 15–17 cover: compositions and method-of-use?

• Claim 15: a composition comprising the Claim 14 modified oligonucleotide + a pharmaceutically acceptable carrier.
• Claim 16: method of administering a therapeutically effective amount for a PKK-associated disease, disorder, or condition.
• Claim 17: enumerates disease/disorder examples, including:
  • Hereditary angioedema (HAE)
  • edema and angioedema variants (lids, ocular, macular, cerebral)
  • thrombotic/embolic conditions (thrombosis, embolism, thromboembolism, DVT, pulmonary embolism, myocardial infarction, stroke, infarct)

This creates enforceable coverage for both drug substance and method-of-use for PKK-associated indications, at least when the accused product uses the Claim 14 oligo.

How do Claims 18–27 lock in specific SEQ ID NOs?

• Claim 18: sequences consisting of SEQ ID NOs 567–575 (closed set).
• Claims 19–27: sequences consisting of SEQ ID NO: 570, applied across dependent claim types:
  • Claim 19: for Claim 1 (sequence consists of SEQ ID NO 570)
  • Claim 20: for Claim 2
  • Claim 21: for Claim 3
  • Claim 22: for Claim 4
  • Claim 23: for Claim 5
  • Claim 24: for Claim 6
  • Claim 25: for Claim 7
  • Claim 26: for Claim 11
  • Claim 27: for Claim 12

This means SEQ ID NO 570 is a central embodiment mapped to multiple chemical features. For design-around, the biggest question is whether a competitor’s lead oligo:

• is SEQ ID NO 570 (or one of 567–575), and
• otherwise meets the same chemistries and complementarity constraints.

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How many distinct patent-claim “invention lanes” exist in 9,670,492?

Lane map (what each lane requires)

1. Core invention lane (Claim 1)

   • Sequence complementarity: ≥8 contiguous perfect complement + ≥90% total complement
   • Length: 12–30
   • Architecture: gap of deoxy; 5′ and 3′ wings with modified sugars

2. Single-stranded lane (Claim 2)

   • Requires single-stranded format

3. Nucleobase-modification lane (Claims 3–4)

   • At least one modified nucleobase; specifically 5-methylcytosine for Claim 4

4. Backbone linkage lane (Claims 5–6)

   • Modified linkages; specifically all phosphorothioate linkages for Claim 6

5. Sugar-chemistry lane (Claims 7–12)

   • Uniform vs mixed modified sugars
   • At least one bicyclic sugar (cEt/LNA/ENA)
   • Or/and 2′-substituted sugar types (2′-OCH3, 2′-F, 2′-O-MOE)

6. Specific embodiment lane (Claims 13–14 and 15)

   • Length 16–20
   • Exact chemical sequence formula with e (2′-O-MOE), mC (5-methylcytosine), d (2′-deoxy), s (phosphorothioate)

7. Indication lane (Claims 16–17)

   • Administration for PKK-associated conditions including HAE and thrombosis/embolism-related events

8. Explicit SEQ ID lane (Claims 18–27)

   • Closed list 567–575 and heavy focus on SEQ ID 570 across multiple dependent hooks

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What generic entry risks exist for oligonucleotide products relative to this patent?

How would an “almost-the-same” oligo avoid Claim 1?

A competitor trying to stay close to the claimed mechanism would look for at least one hard exclusion.

Potential design-around levers (structural)

• Avoid the gap-wing topology: remove the required “gap segment of deoxynucleosides positioned between modified-sugar wings.”
• Alter wing sugar modification class so that the wings no longer have “modified sugars” as required by Claim 1 (note: the claim does not limit to a specific sugar class for Claim 1, so only changing from one modified sugar class to another likely won’t help; a competitor must remove the “modified sugar” premise for Claim 1, or restructure topology).
• Break the phosphorothioate “all linkages” condition to evade Claim 6 (though Claim 1 and Claim 5 could still be implicated depending on linkage structure).

Potential design-around levers (sequence)

• Fail the “≥8 contiguous bases at 100% complementarity” requirement.
• Fail the ≥90% complementarity over the entirety relative to SEQ ID NO: 10.

Because Claim 1’s sequence rules are quantitative, even a single mismatched base within the contiguous block, or too many mismatches overall, can move the product outside claim coverage.

How do claims narrow the risk further for the SEQ ID 570 embodiment?

If a competitor’s oligo is not SEQ ID NO: 570 and not within the closed set 567–575, it weakens the dependent sequence-specific coverage (Claims 18–27). But Claim 1 is still open-ended for complementarity constraints. In practice, the key risk persists if the competitor’s design still satisfies:

• the perfect 8-base complement block to positions 27427–27466 of SEQ ID NO: 10, and
• the ≥90% total complement relationship.

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What formulations and delivery systems are covered by 9,670,492?

What does Claim 15 cover: salts and compositions?

• Claim 15 is broad: “composition” with pharmaceutically acceptable carrier/diluent.
• Claim 28–29 (from your excerpt) specify:
  • Claim 28: composition where modified oligonucleotide is a salt
  • Claim 29: sodium salt

This means salt forms (including sodium salt) do not escape coverage if the oligo itself is within the claimed scope (especially Claim 14 for the composition method claims).

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How strong is the patent estate for this chemistry given only the claim text you provided?

Claim construction leverage points

Even without the specification, the claim text itself indicates strong constraint stacking:

• Architecture + sequence math in Claim 1: two independent constraint systems must both be satisfied.
• Phosphorothioate across all linkages for Claim 6.
• 5-methylcytosine for Claim 4.
• Explicit chemical embodiment (Claim 14) tying modified sugars (2′-O-MOE) and phosphorothioate and 5-methylcytosine to a defined sequence formula.
• Indication claims specifically tie administration to PKK-associated conditions and provide an enumerated clinical disease list in Claim 17.

A competitor must therefore create a substantially different oligonucleotide in either recognition sequence or chemistry/topology to reduce overlap with the most enforceable dependent claims (Claims 14 and 16–17).

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What is missing for a complete US patent landscape analysis around 9,670,492?

The excerpt provides claim language only. A full “landscape” typically requires:

• list of the patent’s related family members and continuations,
• prosecution history and claim amendments,
• specification-dependent sequence mapping for SEQ ID NO: 10 and the precise oligo target,
• citations (prior art, related patents),
• whether 9,670,492 is asserted in litigation and which patents/claims it is paired with.

Under the constraints of this task, those elements cannot be produced from the claim text alone.

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Key Takeaways

• Claim 1 is the central gatekeeper: it requires (i) a defined 12–30 length oligonucleotide with ≥8 contiguous 100% complementary bases and ≥90% global complementarity to SEQ ID NO: 10 positions 27427–27466, and (ii) a gap-wing architecture where the wings have modified sugars and the gap is deoxynucleosides.
• Dependent claims lock specific chemistries: single-stranded (Claim 2), 5-methylcytosine (Claim 4), all phosphorothioate linkages (Claim 6), and sugar classes including cEt/LNA/ENA bicyclic sugars (Claim 10) and 2′-OCH3 / 2′-F / 2′-O-methoxyethyl (Claim 12).
• The most enforceable embodiment is Claim 14: it ties the compound to a specific 2′-O-methoxyethyl (e), 5-methylcytosine (mC), 2′-deoxynucleoside (d), and phosphorothioate (s) chemical pattern.
• Formulation and use claims broaden enforcement: composition with pharmaceutically acceptable carrier (Claim 15) and method of administering for PKK-associated disease including HAE and thromboembolism/MI/stroke (Claims 16–17). Salt forms including sodium salt are covered (Claims 28–29).
• Sequence-specific dependent coverage centers on SEQ ID NO: 570 (Claims 19–27) and a closed group (Claims 18).

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FAQs

1) Does 9,670,492 protect generic “antisense” oligonucleotides, or only specific complementarity rules?
Only those that meet the quantitative complementarity thresholds (≥8 contiguous 100% complement plus ≥90% global complement) against SEQ ID NO: 10 positions 27427–27466, plus the required gap-wing modified-sugar architecture in Claim 1.

2) What is the practical design-around strategy against the strongest dependent claims?
Change the oligo so it does not satisfy Claim 14’s specific chemical pattern (or otherwise avoid the Claim 1 complementarity + architecture combination), and avoid the Claim 6 requirement that all internucleoside linkages are phosphorothioate.

3) Are salts and sodium salts covered?
Yes. Claim 28 covers salt forms, and Claim 29 specifies sodium salt, assuming the underlying oligonucleotide falls within the claimed scope.

4) Which sugar chemistries are specifically called out?
Bicyclic sugars including cEt, LNA, and ENA (Claim 10), and 2′-substituted nucleosides with substituents selected from 2′-OCH3, 2′-F, and 2′-O-methoxyethyl (Claims 11–12).

5) Do the method-of-use claims cover hereditary angioedema?
Yes. Claim 17 expressly lists hereditary angioedema (HAE) and multiple edema/angioedema variants as PKK-associated indications.

Drugs Protected by US Patent 9,670,492

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Ionis Pharms Inc	DAWNZERA (AUTOINJECTOR)	donidalorsen sodium	SOLUTION;SUBCUTANEOUS	219407-001	Aug 21, 2025		RX	Yes	Yes	9,670,492			Y

International Family Members for US Patent 9,670,492

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2014312196
Australia	2019204977
Brazil	112016004093
Canada	2921839
China	105517556