Last Updated: May 11, 2026

Patent: 9,169,212


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Summary for Patent: 9,169,212
Title:Azepane derivatives and methods of treating hepatitis B infections
Abstract: Provided herein are compounds useful for the treatment of HBV infection in a subject in need thereof, pharmaceutical compositions thereof, and methods of inhibiting, suppressing, or preventing HBV infection in the subject.
Inventor(s): Hartman; George D. (Lansdale, PA), Kuduk; Scott (Harleysville, PA)
Assignee: Novira Therapeutics, Inc. (Doylestown, PA)
Application Number:14/511,964
Patent Claims:see list of patent claims
Patent landscape, scope, and claims summary:

United States Patent 9,169,212 (HBV): What the Claims Actually Cover and Where the Landscape Leaks

What is US 9,169,212 claiming at the compound level?

US 9,169,212 is structured as a classic HBV “compound + composition + treatment method” patent. The key constraint is that the scope of the core inventive subject matter is limited to a specific set of enumerated compounds (Claim 1) and then to a set of enumerated structural formula embodiments (Claims 13 to 20). The method claims (Claims 3 to 12) then fold in broad combination-therapy language that does not itself create a novel compound, but can materially extend enforcement leverage depending on what the compound in Claim 1 is and how it is used clinically.

Claim set (high-level)

Claim Type Scope hook
1 Product (compound) Enumerated compounds and salts (shown as Markush list in your excerpt)
2 Product (composition) Claim 1 compound + pharmaceutically acceptable carrier
3 Method Treat HBV infection by administering a therapeutically effective amount of Claim 1 compound
4-12 Method add-ons “Further comprising” combination with specified classes and specific agents
13-20 Product (structural) Additional structural formula embodiments explicitly tied back to Claim 1

Critical implication

If the compound set in Claim 1 is narrow, the overall patent family’s practical value is driven by: 1) whether the enumerated compounds are potent against HBV viral processes in humans at relevant doses, and
2) whether competitors can design around by using non-enumerated analogs or different salt forms, or by using the drug only in regimens not covered by dependent claims.

The dependent method claims broaden the potential clinical use, but they do not expand beyond the Claim 1 compound being used.


How broad are the method claims for combination therapy?

Claims 4 through 12 impose the most enforcement-relevant expansion beyond “treat HBV with compound X.”

Combination therapy language is wide, but only as dependent claims

Claim 4: method of Claim 3 further comprising at least one additional therapeutic agent selected from a long list that includes (verbatim from your excerpt):

  • HBV polymerase inhibitor
  • immunomodulatory agents
  • pegylated interferon
  • viral entry inhibitor
  • viral maturation inhibitor
  • literature-described capsid assembly modulator
  • reverse transcriptase inhibitor
  • a cyclophilin/TNF inhibitor
  • a TLR-agonist
  • an HBV vaccine
  • combination thereof

This is structurally important: it is a Markush list that allows “at least one” agent from a wide set.

Specifics that meaningfully narrow dependent scope

Claims 5 to 10 narrow the “additional agent” to particular agent classes and then to explicit named compounds:

Reverse transcriptase inhibitor branch (Claim 5) Includes nucleos(t)ide analogs such as: Zidovudine, Didanosine, Zalcitabine, dideoxyadenosine (2’,3’-dideoxyadenosine), Stavudine, Lamivudine, Abacavir, Emtricitabine, Entecavir, Apricitabine, Atevirapine, ribavirin, acyclovir, famciclovir, valacyclovir, ganciclovir, valganciclovir, Tenofovir, Adefovir, cidofovir, Efavirenz, Nevirapine, Delavirdine, Etravirine.

TLR agonist branch (Claim 6) Only two explicit examples:

  • SM360320 (listed as 9-benzyl-8-hydroxy-2-(2-methoxy-ethoxy)adenine)
  • AZD 8848 (listed as a methyl [3-({[3-(6-amino-2-butoxy-8-oxo-7,8-dihydro-9H-purin-9-yl)propyl]-[3-(4-morpholinyl)propyl]amino}methyl)phenyl]acetate)

Interferon branch (Claims 7-10)

  • Claim 7: interferon alpha, beta, lambda, gamma
  • Claim 8: interferon-alpha-2a, interferon-alpha-2b, interferon-alpha-n1
  • Claim 9: pegylated interferon-alpha-2a or -2b
  • Claim 10: pegylated interferon-alpha-2a (PEGASYS)

Critical implication for enforcement strategy

  • The “headline” combination claim is Claim 4, and it is broad because it captures many HBV standard-of-care modalities as “additional agents.”
  • But to enforce dependent claims (5-12), the accused regimen has to match the narrowed selections, especially Claim 6’s two TLR agonists and Claim 10’s explicit PEGASYS reference.

From a competitive standpoint, a company can often:

  • avoid the narrow dependents by using different interferon types, non-listed TLR agonists, or different agents not in the enumerated sub-sets; while
  • still potentially fall under Claim 3 (monotherapy) if they administer a Claim 1 compound for HBV.

Where does design-around pressure realistically sit?

1) Claim 1 compound enumeration is the gating element

Claims 2 and 3 are directly dependent on Claim 1. If the competitor avoids using the exact enumerated compound(s) (or their pharmaceutically acceptable salts), Claim 2-3 fall away.

2) Dependent regimens can be engineered to avoid certain narrow recitations

The most “actionable” design-around points are:

  • TLR agonist selection: only SM360320 and AZD 8848 are named in the dependent Claim 6.
  • Pegylation specifics: dependent Claims 9-10 focus on pegylated interferon-alpha-2a/-2b and PEGASYS.

However, Claim 4 still captures “immunomodulatory agents” and “pegylated interferon” broadly. So avoiding only Claim 10 may not remove exposure under Claim 4, depending on the exact therapy.

3) Salt forms and pharmaceutically acceptable salts

Claims explicitly cover “a pharmaceutically acceptable salt thereof.” This typically makes salt-based design-arounds harder unless the competitor uses:

  • a non-pharmaceutically acceptable salt (unlikely to be marketed), or
  • a different crystalline form or prodrug strategy not covered by “salt” terminology, and not covered as the same “compound.”

Without the exact chemical identities shown in your Markush blocks, the strength of salt coverage cannot be fully stress-tested from your excerpt alone.


What does Claims 13 to 20 add beyond Claim 1?

Claims 13-20 recite “structural formula” embodiments that are each “or a pharmaceutically acceptable salt thereof,” tied back to Claim 1.

Critical implication

In many HBV compound patents, these structural claims do three things:

  • they lock in specific chemical scaffolds and substituent patterns (reducing risk that Claim 1’s Markush listing is interpreted narrowly or ambiguously),
  • they support validity arguments if Claim 1 is argued as indefinite or overbroad, and
  • they create multiple independent-looking “embodiment hooks” for claim charts.

Your excerpt shows Claim 13-20 as distinct structural formulas, but the chemical structures themselves are embedded in your text as placeholders (##STR00740## etc.). That means the precise overlap with known chemical space cannot be compared here.


How does the combination-therapy claim set interact with HBV standard of care?

The dependent list in Claim 4 spans major HBV therapeutic modality categories (polymerase inhibitors, interferons, viral entry inhibitors, capsid assembly modulators, vaccines, and immunomodulators). That breadth matters because it increases the chance that at least one widely used regimen could land inside the claim scope.

Key practical outcomes:

  • If Claim 1 compound is a direct-acting HBV antiviral (polymerase, capsid, entry, maturation), it is likely to be used in combinations with other HBV agents.
  • If Claim 1 compound is immunomodulatory or host-directed, it still fits the “immunomodulatory agents” and interferon branches.

But again: enforceability hinges on the accused product administering Claim 1 compound and on the additional agents matching dependent selections if the patentee asserts dependents.


Patent landscape risks: what kinds of prior art typically attack this claim structure

US HBV compound patents usually face the same validity pressure points. US 9,169,212’s claim architecture suggests it is particularly vulnerable if the enumerated compounds map closely to known HBV-related scaffolds.

Likely validity attack vectors (by claim type)

Claim type Common invalidity vectors Why this patent structure is exposed
Claim 1 (compound) novelty/obviousness over prior HBV analogs; obvious modification of known scaffolds; lack of written description for breadth compound is enumerated but still tied to a chemical series; structural claims reinforce specific embodiments but cannot save a genuinely duplicative structure
Claim 2 (composition) obviousness of formulation with known carriers composition claims often rely on the underlying compound being novel/non-obvious
Claim 3 (HBV method) obviousness of using the compound to treat HBV; prior teaching of indication if the compound is known for related antiviral activity, indication-based obviousness can be asserted
Claims 4-12 (combination) obviousness of combination regimen; lack of unexpected synergy “further comprising” language invites combination-obviousness attacks unless the patent record includes strong synergy data

Critical observation on combination claims

Combination therapy claims that list broad classes without requiring a specific dosing schedule, sequence, or mechanistic interaction are commonly attacked as “routine combination” if the prior art suggests combining those modalities in HBV generally.

Claim 4 is broad on purpose. That breadth increases coverage but also increases vulnerability on obviousness.


Freedom-to-operate (FTO): what matters operationally

From an FTO perspective, you should treat US 9,169,212 as two layers of risk:

1) Compound risk (highest): does the candidate drug contain or release a Claim 1 compound in vivo in a manner that satisfies “administering a therapeutically effective amount of a compound of claim 1”?
2) Regimen risk (secondary but real): if the compound is used, does the planned HBV regimen include agents that land inside dependent Claims 4-12?

Regimen risk matrix (based on your excerpt)

Planned combination component Risk vs. dependent claims
Pegylated interferon (general) aligns with Claim 4 and may align with pegylated dependents depending on exact interferon species
PEGASYS specifically high risk for Claim 10 if Claim 1 compound is also administered
TLR agonist other than SM360320 or AZD 8848 lowers risk of Claim 6, but not Claim 4’s broad “TLR-agonist” bucket if asserted
TLR agonist = AZD 8848 or SM360320 matches Claim 6 risk strongly
Reverse transcriptase inhibitors that overlap listed nucleos(t)ides could match Claim 5 depending on the exact agent selection

Key Takeaways

  • US 9,169,212 is gated by Claim 1: enforceability and commercial risk begin and end with whether a competitor administers one of the enumerated Claim 1 compounds (or pharmaceutically acceptable salts).
  • Claim 3 covers HBV treatment with Claim 1 compound as monotherapy: any HBV indication use of the Claim 1 compound can trigger infringement theories.
  • Claim 4 expands into combination therapy broadly using a long Markush list of HBV modalities, increasing the probability that real-world regimens fall within dependent claim scope.
  • Claims 5-10 create narrow “named agent” pressure points (notably the two TLR agonists in Claim 6 and PEGASYS in Claim 10). Avoiding those narrow selections can reduce dependent-claim exposure, but does not negate Claim 3 or the broad Claim 4 framing.
  • Validity exposure is typical for this architecture: compound novelty/obviousness drives everything, and method/combination claims often face “routine use/routine combinations” obviousness arguments unless the underlying disclosure ties the compound to HBV with unexpected effect.

FAQs

1) Does US 9,169,212 primarily cover a compound, or a treatment regimen?

It primarily covers a specific set of compounds (Claim 1) and then extends to HBV treatment methods (Claim 3) using those compounds, with broader combination regimens in dependent claims (Claim 4).

2) What is the biggest design-around lever?

Avoiding administration of the exact Claim 1 enumerated compound(s) (or their pharmaceutically acceptable salts) is the strongest lever because Claims 2-3 depend on Claim 1.

3) Are combination therapy claims broad enough to cover most HBV standard-of-care?

Claim 4 is broad across many HBV modality categories (polymerase inhibitors, interferons, viral entry, capsid modulators, vaccines). Whether a specific regimen fits depends on the exact additional agent(s), with narrower dependents for some selections.

4) Which dependent claims are most specific and easiest to engineer around?

Claim 6 (only SM360320 and AZD 8848) and Claim 10 (PEGASYS) are the most specific. If those agents are excluded, dependent-claim overlap can drop.

5) What drives infringement risk if a competitor uses the same compound but different HBV combinations?

Claim 3 can still be implicated if the competitor uses the Claim 1 compound for HBV, while dependent combination claims (4-12) turn on whether the added agent choices match the recited selections.


References

[1] United States Patent No. 9,169,212.

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Details for Patent 9,169,212

Applicant Tradename Biologic Ingredient Dosage Form BLA Approval Date Patent No. Expiredate
Merck Sharp & Dohme Llc RECOMBIVAX, RECOMBIVAX HB hepatitis b vaccine (recombinant) Injection 101066 July 23, 1986 ⤷  Start Trial 2034-10-10
Glaxosmithkline Biologicals ENGERIX-B hepatitis b vaccine (recombinant) Injection 103239 August 28, 1989 ⤷  Start Trial 2034-10-10
Pharmaand Gmbh PEGASYS peginterferon alfa-2a Injection 103964 October 16, 2002 ⤷  Start Trial 2034-10-10
Pharmaand Gmbh PEGASYS peginterferon alfa-2a Injection 103964 January 07, 2004 ⤷  Start Trial 2034-10-10
Pharmaand Gmbh PEGASYS peginterferon alfa-2a Injection 103964 September 29, 2011 ⤷  Start Trial 2034-10-10
Hoffmann-la Roche Inc. PEGASYS COPEGUS COMBINATION PACK peginterferon alfa-2a and ribavirin 125083 June 04, 2004 ⤷  Start Trial 2034-10-10
Schering Corporation A Subsidiary Of Merck & Co., Inc. PEGINTRON/ REBETOL COMBO PACK peginterferon alfa-2b and ribavirin 125196 June 13, 2008 ⤷  Start Trial 2034-10-10
>Applicant >Tradename >Biologic Ingredient >Dosage Form >BLA >Approval Date >Patent No. >Expiredate

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