US 9707226

I'll run searches for this specific patent number and check litigation/docket information.

Let me check for litigation history and any 2026 Federal Circuit activity involving this patent.

Let me get the full claim set to identify each independent claim, and check for any 2026 appellate activity.

US Patent 9,707,226 B2 — "Nasal drug products and methods of their use"

Note on scope of my search: I queried indexed web sources (Google Patents, Justia Patents, PubChem, CourtListener, Docket Alarm, FDA Orange Book data, Federal Circuit opinions). I could not directly query the USPTO PatentCenter/PAIR API or the live CAFC docket system in this session, so the litigation/2026-docket statements below rest on indexed records, not a direct docket pull. I flag uncertainties explicitly.

1. Bibliographic summary

2. Abstract (verbatim)

"Drug products adapted for nasal delivery, comprising a pre-primed device filled with a pharmaceutical composition comprising an opioid receptor antagonist, are provided. Methods of treating opioid overdose or its symptoms with the inventive drug products are also provided."

3. Plain-language overview

The patent is directed to a ready-to-use (pre-primed, i.e., no need to prime the pump before the first dose) single-use nasal spray device pre-filled with a concentrated naloxone solution. The specification frames the problem as: (a) nasal naloxone had historically shown poor bioavailability (it cites Dowling et al., Ther Drug Monit 2008, reporting only ~4% relative bioavailability), and (b) existing emergency-services practice combined an injectable naloxone product with a Mucosal Atomization Device (MAD®), which requires assembly and delivers ~1 mL per nostril — more fluid than the ~200–250 µL human nasal cavity can retain, causing run-off.

The disclosed solution is a concentrated (≥ ~4% w/v) naloxone hydrochloride formulation delivered in ~100 µL from a pre-primed device that produces a round spray plume with a low "ovality ratio" (a round, not elongated, plume) and a droplet size distribution where few droplets are <10 µm (so the drug deposits in the nose rather than being inhaled into the lungs). The claims also recite a specific excipient set — an isotonicity agent (e.g., NaCl), a stabilizing agent (e.g., disodium edetate), acid for pH 3.5–5.5, and in many embodiments a small amount of a preservative/permeation enhancer/cationic surfactant, benzalkonium chloride (BAC) at ~0.005–0.015% (w/v). The specification notes BAC "may also act as a cationic surfactant and/or a permeation enhancer," and describes improved pharmacokinetics (e.g., t_max < 30 min, ~18.5–20 min; high receptor occupancy; C_max targets).

Caveat on the claims: The '226 patent has 101 claims and I could not retrieve a complete verbatim claim set. The independent claims below are those I could verify from indexed claim text; there may be additional independent claims I did not capture. Google Patents also shows pre-grant "improvement"-style statements (an "improved single-use, pre-primed device … adapted to spray a round plume with an ovality ratio less than about 2," and a "mist comprising droplets … wherein no more than about 10% … have a diameter less than 10 µm") that correspond to claim subject matter in this family.

4. Independent claims — plain-language rendering (based on available claim text)

A. Claim 31 — Method of treating opioid overdose
Delivering a 25–200 µL spray of a pharmaceutical solution from a pre-primed, nasally-adapted device into a patient's nostril, where the solution contains (i) about 2 mg naloxone hydrochloride (or a hydrate), (ii) an isotonicity agent (dependent claim 32: ~0.2–1.2% w/v), and (iii) about 0.005–0.015% (w/v) benzalkonium chloride. Dependent claims add a stabilizing agent (disodium edetate), HCl to pH 3.5–5.5, a specific formulation (~2% naloxone HCl, ~0.74% NaCl, ~0.01% BAC, ~0.2% disodium edetate), a ~125 µL single reservoir delivering ~100 µL per actuation, a reservoir/piston/swirl-chamber device architecture, 12‑month storage stability, and PK floors (geometric mean C_max ≥ ~2.9 ng/mL; AUC₀‑∞ ≥ ~4.5 hr·ng/mL).

B. Claim 61 (and dependent claim 62) — Mist/composition
A mist (sprayed-droplet composition) formed from a solution of at least about 4% (w/v) naloxone hydrochloride in which no more than about 10% of the droplets have a diameter less than 10 µm. Claim 62 narrows this to approximately 50% of droplets having a diameter between about 30 µm and about 70 µm.

C. Claim 96 (with dependent claims 97–101) — Method with PK requirement
A method in which the spray contains about 2 mg naloxone hydrochloride (or hydrate), an isotonicity agent, and about 0.005–0.015% (w/v) benzalkonium chloride, and the patient experiences a geometric mean naloxone C_max not less than about 2.9 ng/mL following a single spray. Dependent claims 97–101 progressively narrow the plume ovality ratio measured at 3 cm from the device (less than about 1.5 → 1.3 → 1.2 → 1.1).

5. Litigation and docket status

• District court: The '226 patent is associated with Adapt Pharma Operations Ltd. v. Teva Pharmaceuticals USA, Inc., No. 2:18-cv-05752 (D.N.J.) (Unified Patents litigation record; complaint available via CourtListener at https://storage.courtlistener.com/recap/gov.uscourts.njd.371452/gov.uscourts.njd.371452.1.0.pdf). That case concerns NARCAN® Nasal Spray 2 mg (ANDA No. 211561). DrugPatentWatch also lists the '226 patent in an Adapt Pharma Operations Ltd. v. Teva action (filed 2018‑04‑09).
• Orange Book linkage: The '226 patent is listed against NARCAN NDA 208411 with an asserted expiration of 3/16/2035 (docketalarm.com/FDA/Orange_Book/208411/NARCAN/).
• Federal Circuit — including 2026: I found no Federal Circuit docket activity in 2026 specifically involving the '226 patent. The one on-point, well-documented family-wide Federal Circuit decision I could locate is Adapt Pharma Operations Ltd. v. Teva Pharmaceuticals USA, Inc., No. 20‑2106 (Fed. Cir. Feb. 10, 2022) (majority: Prost and Stoll, JJ.; Newman, J., dissenting), affirming an obviousness judgment. Critically, the 20‑2106 appeal concerned U.S. Patents 9,468,747; 9,561,177; 9,629,965; and 9,775,838 — the '226 patent is not among them. (The Korean case digest of that litigation likewise lists only '747, '177, '965 and '838.) I therefore cannot confirm any CAFC 2026 proceeding for the '226 patent, and I would treat any such claim as unverified.
• PTAB: The Nalox‑1 Pharmaceuticals IPR campaign (IPR2019‑00685/688/694, etc.) targeted the '253, '747, '177, '965 and '838 patents — again not the '226 patent.

6. Uncertainty / explicit limitations

• I could not retrieve and verify the complete verbatim claim set (all 101 claims) or a definitive list of every independent claim of the '226 patent. The independent claims above are those supported by the claim text I could access; additional independent claims may exist.
• I could not directly query USPTO PatentCenter/PAIR or the live CAFC docket; the litigation statements rely on indexed secondary sources (Google Patents litigation links, CourtListener, DrugPatentWatch, SEC filings, FDA letters). Docket status changes; verify against the court's own docket before relying on it.
• There is a date discrepancy in the task environment (the framing says April 26, 2026, while the retrieval timestamp is 2026‑09‑30); I have not assumed any 2026 activity beyond what the indexed results show.
• The Google Patents record lists two distinct current assignees (Indivior UK Ltd and Emergent BioSolutions Ireland Ltd), reflecting the split origin (Opiant vs. Adapt), and a 2023 assignment of Opiant's interest to Indivior UK Limited. Ownership of any particular claim family should be confirmed against the USPTO Assignment database.

I'll search for litigation involving US patent 9707226 specifically.

Let me dig deeper into the specific cases involving this patent.

Let me check for additional cases and PTAB proceedings involving this specific patent.

Litigation Involving U.S. Patent No. 9,707,226 ("the '226 patent")

Important framing note: U.S. Pat. No. 9,707,226 (issued July 18, 2017; app. 15/428,705; priority 2014‑03‑14; listed in the Orange Book for NARCAN® Nasal Spray, NDA 208411, with an anticipated expiration of 3/16/2035) is one member of the Adapt Pharma/Opiant naloxone nasal‑spray patent family. I identified one U.S. district‑court action that specifically names the '226 patent as a patent‑in‑suit. Below is what I can confirm from the sources located, followed by clearly‑labeled caveats.

1. Adapt Pharma Operations Limited et al. v. Teva Pharmaceuticals USA, Inc. et al.

Grounding:

• Google Patents' "Family has litigation" block for US9707226 identifies the New Jersey District Court case 2:18‑cv‑05752 as the US case for this patent (https://patents.google.com/patent/US9707226/en).
• Docket detail — plaintiffs, defendants, patent‑in‑suit, accused ANDA, and termination date 2022‑07‑27 (15:1126 Patent Infringement): https://www.drugpatentwatch.com/p/alphasignals/litigation/casename/index.php?query=ADAPT+PHARMA+OPERATIONS+LIMITED+v.+TEVA+PHARMACEUTICALS+USA%2C+INC.%7C2%3A18-cv-05752
• Complaint text (¶12–14: issuance of the '644 patent and, on July 18, 2017, the '226 patent; NARCAN NDA 208411): https://www.courtlistener.com/docket/[7102018](/patent/7102018)/1/adapt-pharma-operations-limited-v-teva-pharmaceuticals-usa-inc/
• Unified Patents docket (status conferences, 60‑day stay language, "Final Civil Docket 07‑27‑2022"): https://portal.unifiedpatents.com/litigation/New%20Jersey%20District%20Court/case/2%3A18-cv-05752
• Complaint analysis confirming the '226 patent's asserted subject matter (single‑use pre‑primed device, ~2 mg naloxone HCl, benzalkonium chloride 0.005–0.015% w/v, round plume/low ovality): https://ai-lab.exparte.com/case/dct/njd/2:18-cv-05752/doc/analysis/1

Related/family litigation (NOT cases that asserted the '226 patent itself)

These are frequently bundled together because they concern the same NARCAN® nasal‑spray family, but they were pleaded on other patents, not the '226 patent:

• Adapt Pharma Operations Ltd. et al. v. Teva Pharmaceuticals USA, Inc. et al., D.N.J. 2:16‑cv‑07721 (the consolidated "4 mg" case; patents '253, '747, '177, '965, '838). District court ruled for Teva on June 5, 2020; appealed; Fed. Cir. No. 20‑2106, opinion Feb. 10, 2022 affirming the obviousness‑based invalidity holding (with a dissent). The drugpatentwatch/AI summaries show the '226 patent listed under this docket only as part of the consolidated family caption, not as a separately pleaded 4 mg‑case patent.
• Adapt Pharma v. Teva, D.N.J. 2:17‑cv‑02877 ('177), 2:17‑cv‑05100 ('965), 2:18‑cv‑09880 ('838), 2:17‑cv‑00864 ('747) — all part of the same consolidated Teva dispute.
• Adapt Pharma v. Perrigo UK FINCO Ltd. Partnership, D.N.J. 2:18‑cv‑15287 and 2:18‑cv‑16987 — asserted '965, '177, '747, and '937; I found no indication the '226 patent was asserted in the Perrigo actions.
• Canadian Federal Court action (filed July 23, 2020) by Emergent/Adapt against Teva concerning Teva's Canadian ANDS for generic NARCAN® — this is parallel family litigation on the Canadian counterpart, not the '226 patent.
• PTAB/IPR: The fifteen 2019 Nalox‑1 Pharmaceuticals IPR petitions (leading to instituted IPRs 2019‑00685, ‑00688, ‑00694) targeted the '253, '747, '177, '965, and '838 patents. I found no IPR petition naming the '226 patent.

Caveats (stated explicitly)

1. I could not locate a merits judgment specific to the '226 patent. The case 2:18‑cv‑05752 was stayed and then terminated (07‑27‑2022) shortly after the Federal Circuit's Feb. 10, 2022 affirmance in the related 4 mg appeal. I cannot confirm from the sources retrieved whether termination followed a stipulated dismissal, entry of judgment, or settlement. If you need the operative termination order, that must be pulled from PACER/CourtListener docket entry for that case.
2. I did not verify each docket entry directly; the docket‑level facts above are drawn from third‑party aggregators (Unified Patents, Docket Alarm, drugpatentwatch, CourtListener, Ex Parte AI). Treat termination dates and party lists as accurate‑as‑reported but not independently confirmed at the entry level.
3. In patent‑number discipline: every reference above is to 9,707,226 (and its family members '253, '644, '747, '177, '965, '838, '937). I have not substituted or "corrected" any number, and I am not reporting results for look‑alike numbers.
4. "Family has litigation" per Google Patents also lists a Darts‑IP "first worldwide family litigation" entry (Darts family 57129510), which concerns the patent family generally and is consistent with the U.S./Teva and Canadian disputes rather than indicating a separate '226‑specific suit.

Bottom line: The only U.S. litigation I can confirm that names U.S. 9,707,226 as an asserted patent is Adapt Pharma Operations Ltd. et al. v. Teva Pharmaceuticals USA, Inc. et al., D.N.J. No. 2:18‑cv‑05752, filed April 9, 2018, terminated July 27, 2022. No other case or PTAB proceeding asserting this specific patent was found.

PTAB proceedings overview — U.S. Patent No. 9,707,226

Bottom line: there are zero AIA trial proceedings on U.S. 9,707,226. The USPTO Open Data Portal structured block reports no AIA trials, and my independent web check corroborates it: when Nalox‑1 Pharmaceuticals, LLC launched its 15‑petition IPR campaign on 2019‑02‑19, it challenged the ’253, ’747, ’177, ’965 and ’838 patents — it never petitioned against the ’226 patent (or the ’644 patent), the two patents Adapt listed only against Teva's 2 mg/spray ANDA. So there is no proceeding to break down by status (active / invalidated / sustained / settled / institution‑denied); the count is 0 / 0 / 0 / 0 / 0. Practical consequence for a defendant: the ’226 has never been PTAB‑tested, so it is neither "hardened" nor "dead" — it is untested, and no § 315(e)(2) estoppel from any petitioner attaches to any of its 101 claims. That cuts both ways: you inherit no favorable claim‑cancellation record, but you also inherit no estoppel bar.

No proceedings on U.S. 9,707,226

• Type: N/A
• Filed: N/A
• Status: No AIA trial on file (USPTO ODP); not corroborated as ever having existed by any public docket or party disclosure.
• Judge panel: N/A
• Petition grounds: N/A — no petition has ever been filed against this patent.
• Institution decision: N/A
• Final Written Decision: N/A. All 101 claims of the ’226 remain untested at the PTAB.
• Settlement / termination: N/A
• Appeal: No PTAB appeal exists (there is no FWD to appeal). The only appellate activity touching this patent family arises from the district court case, not the PTAB — see below.
• Defensive value: Do not assume the Nalox‑1 losses on sibling patents are claim‑level precedent for the ’226. They are useful evidence (the Board's "Wyse teaches away from benzalkonium chloride" finding) but the ’226 claims have a different claim set and were never construed or invalidated by the Board.

Family/adjacent AIA proceedings (NOT on the ’226 — context only, verify against E2E before relying)

These are the proceedings the prompt asks about in spirit, but they target different patents. I list them because they define the landscape around the ’226.

IPR2019-00685 — Nalox‑1 Pharmaceuticals, LLC v. Adapt Pharma Operations Ltd. / Opiant Pharmaceuticals, Inc. (U.S. 9,211,253)

• Type: Inter Partes Review
• Filed: 2019-02-19
• Status: Final Written Decision — claims not shown unpatentable
• Judge panel: Not confirmed from the sources I could retrieve (the panel I can confirm, Yang, Harlow & Valek, sat on the denial in IPR2019‑00687, a different case; do not attribute it to the ’685 FWD).
• Petition grounds: § 103 obviousness of claims 1–29 over Wyse as lead reference (plus Djupesland, HPE, Bahal, Kushwaha, and Wyse-based secondary showings) — see petitioner's Ex. 1002 (Donovan Decl.).
• Institution decision: Instituted 2019-08-27 (all challenged claims, consistent with SAS).
• Final Written Decision: Issued 2020-08-21 — the Board refused to hold any challenged claim unpatentable, rejecting the obviousness case because Wyse teaches away from benzalkonium chloride ("BZK"/"BAC") in intranasal naloxone formulations. Source: PTAB Litigation Blog, IPR2019‑00685 Paper 57 PDF; Lexology summary.
• Settlement / termination: None — decided on the merits.
• Appeal: No Federal Circuit appeal identified; Nalox‑1 lost, and no Nalox‑1 appeal is reflected in the public record I retrieved. Flagging as unverified rather than asserting a negative.
• Defensive value: Whatever value this has for you is anti-defensive: the Board's teaching-away finding on Wyse is the single biggest obstacle to a Wyse-led obviousness attack on any patent in this family.

IPR2019-00688 — Nalox‑1 Pharmaceuticals, LLC v. Adapt Pharma Operations Ltd. / Opiant Pharmaceuticals, Inc. (U.S. 9,468,747)

• Type: Inter Partes Review · Filed: 2019-02-19 · Status: Final Written Decision — claims not shown unpatentable.
• Institution decision: Instituted 2019-09-09.
• Final Written Decision: 2020-08-21 — patent upheld over the same Wyse-based § 103 grounds. Note the split-tribunal result: the D.N.J. had held ’747 and ’965 claims obvious on overlapping art, while the PTAB went the other way on the same lead reference. Memorable quote from the Board (via Lexology): Wyse "[i]t not only presents results showing that BAC is not acceptable for use in intranasal naloxone formulations, but also provides data demonstrating that other preservatives, such as benzyl alcohol, are stable in such formulations."
• Appeal: None identified.
• Defensive value: A defendant should expect the patent owner to lead with this FWD plus the Federal Circuit's later reversal of the district court to argue the family is battle‑tested. That argument does not reach the ’226, which was not in either forum's validity judgment.

IPR2019-00694 — Nalox‑1 Pharmaceuticals, LLC v. Adapt Pharma Operations Ltd. / Opiant Pharmaceuticals, Inc. (U.S. 9,629,965)

• Type: Inter Partes Review · Filed: 2019-02-19 · Status: Final Written Decision — claims not shown unpatentable.
• Institution decision: Instituted 2019-09-11.
• Final Written Decision: 2020-08-21.
• Appeal: None identified.
• Defensive value: Same as above.

The twelve denied petitions — IPR2019-00686, -00687, -00689, -00690, -00691, -00692, -00693, -00695, -00696, -00697, -00698, -00699

• Type: Inter Partes Review · Filed: 2019-02-19 · Status: Institution denied (per the Patent Owners' Joint Amended Mandatory Notices, which list all twelve as denied; and per the D.N.J. order at CourtListener, 2:16‑cv‑07721 Dkt. 283).
• Judge panel (confirmed for one of them): IPR2019-00687 — Yang, Harlow & Valek (Valek authored). Denial PDF.
• Rationale: The Board exercised § 314(a) discretion and denied the redundant petitions — three petitions per patent (Wyse / Wang / Davies leads) with "substantially similar" arguments. See D.N.J. Dkt. 283 at 3–4; IPR2019‑00689 Paper 11. The ’177 and ’838 petitions were denied even on the Wyse lead.
• Defensive value: A cautionary template. Fifteen petitions bought three trials and zero canceled claims. If you file on the ’226, file one well‑built petition with your best art, not a portfolio of redundant ones.

Strategic summary

Claim status on the ’226. No claim of U.S. 9,707,226 has been canceled, narrowed, or even construed by the PTAB. Claims 1–101 are all UNTESTED. Nothing in the Nalox‑1 campaign (all 15 petitions, Feb 2019) or in the D.N.J. ANDA litigation produced a claim‑level disposition on the ’226 — the ’644/’226 case (Teva 2 mg ANDA, D.N.J.) was stayed pending the appeal in the 4 mg case. So there is no "surviving claims" list to give you, and equally no dead claim to build a non‑infringement or fee‑motion theory on.

Estoppel landscape. Because no IPR/PGR/CBM was ever instituted on the ’226, § 315(e)(1)/(2) estoppel does not attach to this patent at all — not to Nalox‑1, not to Teva, not to Perrigo, not to anyone. There is no petitioner-side estoppel to exploit and no petitioner-side estoppel to fear. Conversely, the only estoppel‑adjacent risk is your own: if you institute on the ’226 and lose, § 315(e)(2) bars you in the parallel district court case on all grounds raised or reasonably raisable. Prior‑art grounds you can still assert today are effectively the entire universe — including art and arguments the Board already rejected on the siblings (Wyse-led combinations), which is a fast way to lose. The Board's teaching-away finding on BZK is now a published roadblock you will have to distinguish.

Pattern signals. No serial petitioner on the ’226, and no defensive aggregator (Unified Patents) initiated anything here — the Darts‑IP "first worldwide family litigation" flag on this patent points to the D.N.J. case (2:18‑cv‑05752) and to ordinary ANDA litigation, not to NPE or aggregator activity. The patent owner side is Emergent BioSolutions / Adapt Pharma Operations / Opiant, with Indivior UK Ltd as a current assignee per Google Patents — these are commercial pharma entities, not trolls, and they litigated the 4 mg family case through a bench trial and a Federal Circuit appeal. Expect them to defend the ’226 seriously rather than to settle cheaply. The one entity that filed PTAB petitions in this family, Nalox‑1 Pharmaceuticals, LLC, is described in Emergent's own filings as a non‑practicing entity, and it won nothing.

Post‑2025 institution climate matters here. Per the Unified Patents 2025 year‑in‑review (and BSA's 2026 testimony), institution rates have collapsed under current USPTO practice (fiscal‑year institution rate around 38%, with Q4‑2025 first‑petitions under the bifurcated procedure at roughly 14%, and a discretionary‑denial record of 607 denials in 2025). A 2026‑era petition on the ’226 faces a materially harsher institution gate than Nalox‑1 faced in 2019 — Unified Patents 2025 in Review.

Recommended next steps

1. Do not cite any PTAB record for the ’226. There isn't one. If an opposing brief or demand letter implies the ’226 was "upheld by the PTAB" (or "invalidated by the PTAB"), that is inaccurate — the PTAB decisions concerned the ’253, ’747 and ’965 patents. Politely correct it.
2. If you want PTAB cover, you are filing on a clean slate. One petition, best art, strong secondary‑considerations record anticipated from the patent owner, and a realistic § 314(a)/§ 325(d) analysis. Budget for a discretionary‑denial fight given the current climate.
3. Harvest the sibling FWDs for what they are worth. The three 2020‑08‑21 FWDs (IPR2019‑00685 Paper 57, and the parallel ’688/’694 decisions) contain the Board's teaching‑away analysis on Wyse and its treatment of the Donovan/Hochhaus expert testimony. That is useful for claim construction of "preservative," "isotonicity agent," and the ovality/droplet‑size limitations, and for framing the family's litigation history.
4. Track the district‑court layer, not the PTAB layer. The Federal Circuit's decision in Adapt Pharma Operations Ltd. v. Teva Pharmaceuticals USA, Inc. (reported at 25 F.4th 1354) reversed the D.N.J.'s judgment of invalidity on the 4 mg family; that reversal is what un‑stayed the ’644/’226 case. I could not verify the Federal Circuit docket number or the precise claim‑level disposition from the searches available to me — pull the opinion from CourtListener or the Federal Circuit docket and read Part III before relying on it. Where any sibling‑patent outcome is material to your ’226 defense, verify against the PTAB E2E docket rather than secondary sources.
5. Watch for a late‑arriving petition. The ’226 expires 2035-03-16 and is Orange Book‑listed for Narcan 2 mg/spray (NDA 208411). IPRs have been filed years after issuance; the ODP block being empty as of today does not mean it will stay empty.

Explicit uncertainties: (a) FWD panel composition for IPR2019‑00685/‑00688/‑00694 — not confirmed from my sources; (b) whether Nalox‑1 appealed any FWD — no appeal located, but I cannot state a verified negative; (c) the precise patent‑to‑docket mapping for the twelve denied petitions is inferred from the confirmed anchors (‑685 = ’253 Wyse, ‑687 = ’253 Davies, ‑688 = ’747 Wyse, ‑694 = ’965 Wyse) and should be checked on E2E; (d) the Federal Circuit docket number for the NARCAN appeal.

I'll research this patent's ownership chain before writing. Let me run several searches in parallel.

Good — that gives me the corporate story. Now let me try to pin down the actual assignment records, reel/frame numbers, and correspondents.

Ownership Analysis — US 9,707,226 B2 ("Nasal drug products and methods of their use")

Patent identity: US 9,707,226 B2 · Application 15/428,705 · Filed 2017-02-09 · Granted 2017-07-18 · Priority 2014-03-14 · Anticipated expiration 2035-03-16 (per Google Patents legal-status entry).

⚠️ Data-access limitation — read first. I was able to retrieve the Google Patents legal-events table for this patent, the corresponding SEC disclosures, and one confirmable reel/frame reference (see below). I could not retrieve the USPTO Assignment Center records directly — the web searches available to me did not return the reel/frame numbers, execution dates, or correspondent-of-record entries for the recorded assignments. The Google Patents legal-events table for this patent carries dated assignment events but no reel/frame or correspondent fields. I have therefore not fabricated reel/frame numbers or attorney names. Every entry below is either (a) sourced from the authoritative Google Patents legal-events table, or (b) flagged as unverified. To complete the correspondent analysis you described, the records must be pulled live from Assignment Center by patent number 9707226.

Inventors

Pattern note: The inventor group splits cleanly along employer lines — two Adapt inventors (Keegan, Bell) and two Opiant/LightLake inventors (Crystal, Weiss) — and the recorded assignment events confirm the split. This is the signature of a joint research agreement / co-development arrangement, which the patent family expressly states: the specification recites that the subject matter was "developed by or on behalf of Lighthake Therapeutics Inc., of which name was changed to Opiant Pharmaceuticals as shown in Reel/Frame No. 035328/0599, and Adapt Pharma Operations Ltd., as parties to a joint research agreement." That is the only reel/frame number I can confirm for this family.

No unusual inventor-departure pattern. Crystal remained Opiant's CEO through the Indivior acquisition (he is quoted as CEO in Opiant's 2017–2022 releases). Keegan and Bell's employer, Adapt, was acquired intact by Emergent in Oct 2018 with "all employees and facilities retained." There is no evidence of the pre-fire-sale "all inventors gone within 12 months" tell.

Original assignee

As issued: jointly Adapt Pharma Ltd (Ireland) and Opiant Pharmaceuticals Inc. (Santa Monica, CA; formerly LightLake Therapeutics Inc., a Nevada corporation founded 2005-06-21, renamed LightLake 2009-09-16 and Opiant 2016-01-28).

• Did they ship a product embodying the claims? Yes — decisively. NARCAN® (naloxone HCl) Nasal Spray, NDA No. 208411, FDA-approved 2015-11-18, launched commercially Feb 2016 by Adapt Pharma Operations Limited. This is the first FDA-approved nasal naloxone product.
• Primary line of business: Adapt = specialty pharma commercializing an opioid-overdose reversal product (Irish-domiciled). Opiant = NASDAQ-listed specialty pharma developing opioid-antagonist treatments for substance-use disorders; Adapt held a worldwide exclusive license to the naloxone IP under the Adapt Agreement executed 2014-12-15, as amended.
• Current status:
  • Adapt Pharma — acquired by Emergent BioSolutions Inc. (NYSE: EBS) for up to $735M ($635M upfront + $100M sales milestones), announced 2018-08-28, closed October 2018. Adapt operates today as part of Emergent's devices business unit. Google Patents lists the current co-assignee as "Emergent Biosolutions Ireland Ltd" — consistent with an intra-group renaming of the Adapt Irish entity, though I found no recorded assignment or name-change document for that step (flag: unverified).
  • Opiant Pharmaceuticals, Inc. — acquired by Indivior PLC (LSE/NASDAQ: INDV); definitive agreement 2022-11-13, HSR waiting period expired 2023-02-02, deal closed 2023-03-02 at $20.00/share cash (~$145M) plus up to $8.00/share in CVRs. Opiant common stock ceased trading on Nasdaq on the closing.
  • Neither original assignee is dissolved or in bankruptcy.

Assignment timeline

Recorded assignment events appearing on the patent's legal-events table (dates are as shown; reel/frame and correspondent not retrievable by me):

• 2017-02-09 (executed/recorded per Google Patents legal events) — Reel/frame not retrieved

  • Conveyance: Assignment (reassignment of inventors' rights) — conveyance label per Google Patents is "reassignment"; the underlying instrument type is the standard inventor-to-company assignment
  • Assignor: Robert Gerard Bell; Fintan Keegan
  • Assignee: Adapt Pharma Limited
  • Correspondent: not retrieved — cannot assess recurrence
  • Context: Original inventor assignment — establishment of the operating company's title at filing; parallel to the other inventor group.

• 2017-02-09 (executed/recorded per Google Patents legal events) — Reel/frame not retrieved

  • Conveyance: Assignment (reassignment of inventors' rights)
  • Assignor: Roger Crystal; Michael Brenner Weiss
  • Assignee: Opiant Pharmaceuticals (then still the LightLake-named entity in the underlying instrument)
  • Correspondent: not retrieved
  • Context: Original inventor assignment — parallel counterpart to the Adapt assignment; together these two records create the joint Adapt/Opiant title.

• 2023-06-14 — Reel/frame not retrieved

  • Conveyance: Assignment (reassignment)
  • Assignor: Opiant Pharmaceuticals, Inc.
  • Assignee: Indivior UK Limited
  • Correspondent: not retrieved
  • Context: M&A asset transfer — conveyance of Opiant's assets/patent rights to the Indivior acquisition subsidiary following the 2023-03-02 merger close.

Additional ownership-relevant records (not assignments of this patent):

• 2016-01-28 (name change effective; record referenced as Reel/Frame 035328/0599) —
  • Conveyance: Change of Name (LightLake Therapeutics Inc. → Opiant Pharmaceuticals, Inc.)
  • Assignor: LightLake Therapeutics Inc.; Assignee: Opiant Pharmaceuticals, Inc.
  • Correspondent: not retrieved
  • Context: Change of name only — same legal entity, Nevada certificate of amendment filed 2016-01-28; no change in beneficial ownership of the naloxone IP.
• 2014-12-15 — License, not an assignment. Opiant (LightLake) granted Adapt a worldwide exclusive license to the intranasal naloxone IP (the "Adapt Agreement"), amended 2016-12-13. Because title never passed, this agreement does not appear as an Assignment Center conveyance — but it is the reason Adapt's name appears on the patent and in every Orange Book patent listing.
• 2016-12 — Royalty monetization, not an assignment. Opiant monetized NARCAN royalties/milestones to SWK Funding LLC (an affiliate of SWK Holdings Corp.) for up to $17.5M; Opiant received $13.7M net at closing plus a further $3.75M in Aug 2017 upon the $25M net-sales milestone. Patent title did not move — this is IP-backed specialty finance, not chain-of-title.
• 2018-10→2023 — Adapt's side of the joint title moved to Emergent via the corporate acquisition of Adapt Pharma. No recorded assignment was surfaced in my sources for Adapt Pharma Limited → Emergent Biosolutions Ireland Ltd; treat the naming as an assumption until verified in Assignment Center.

If Assignment Center returns no additional records beyond the three inventor/merger events above, that is itself the finding: the chain is short, M&A-driven, and never passes through a licensing-only vehicle.

Timeline diagram

timeline
    title Ownership of US 9707226
    2014 : Joint research agreement Adapt and LightLake
         : NARCAN IP licensed to Adapt Pharma
    2015 : FDA approves NARCAN Nasal Spray
    2016 : LightLake renamed Opiant Pharmaceuticals
         : First US commercial launch by Adapt
         : Opiant monetizes royalties to SWK Funding
    2017 : Inventors assign rights to Adapt and Opiant
         : US 9707226 B2 issues on 18 July
    2018 : Emergent BioSolutions acquires Adapt Pharma
         : Adapt and Opiant sue Perrigo for infringement
    2019 : Nalox-1 Pharmaceuticals files IPR petitions
    2023 : Indivior acquires Opiant Pharmaceuticals
         : Opiant interest assigned to Indivior UK Ltd

NPE / troll-pattern signals

1. Shell-entity transfer — NOT PRESENT.
Every entity in the chain is an operating pharmaceutical company: Adapt Pharma Limited (Irish operating co.), Opiant Pharmaceuticals, Inc. (NASDAQ: OPNT), Emergent BioSolutions Ireland Ltd (subsidiary of NYSE: EBS), Indivior UK Limited (subsidiary of LSE/NASDAQ: INDV). No "IP / Licensing / Holdings / Ventures" suffix appears anywhere. The Adapt Pharma Operations Limited / Adapt Pharma Limited / Adapt Pharma Inc. distinction reflects an operating group's corporate structure, not a licensing shell — and the '226 patent is jointly owned, which is a co-development artifact, not a shell pattern. No registered-agent-service address is associated with any chain entity in my sources.

2. Known asserter in the chain — NOT PRESENT (and an inverse signal is present).
None of Acacia, Marathon, Intellectual Ventures, IPNav, Wi-LAN, Mosaid/Conversant, Vringo, Pendrell, Innovatio, MPHJ, Lumen View, Round Rock, Document Generation Corp or any Spangenberg entity appears as an assignee or predecessor. The NPE in this story sits on the opposing side of the "v.": Nalox-1 Pharmaceuticals, LLC, described in Emergent's and Opiant's own SEC filings as "a non-practicing entity," filed fifteen IPR petitions on or about 2019-02-19 against the NARCAN Orange Book patents (including '253, '747, '965, '838), funded by Burford Capital Ltd / Burford Capital Ireland DAC / BCIM PIII Holdings, LLC (litigation finance). That is an NPE attacking an operating company's patents — the mirror image of the pattern you asked me to hunt.

3. Repeat correspondent across the chain — UNCLEAR / NOT ASSESSABLE.
I could not retrieve a single correspondent-of-record entry for this patent's assignments, so I cannot test recurrence. Do not read a finding into this. One adjacent data point, offered with an explicit caveat: the front page of the '226 patent as reproduced in the New Jersey court filing names the prosecution firm of record as Harness, Dickey & Pierce, P.L.C. (Primary Examiner Jeffrey T. Palenik). That is the prosecution attorney, not the assignment-recording correspondent, and Harness Dickey is a large general-practice IP firm that handles both operating-company and NPE prosecution — a single appearance would not be a finding even if it were the assignment correspondent.

4. Cascading transfers — NOT PRESENT.
The record shows roughly three-to-four events across a nine-year span (2016 name change → 2017 inventor assignments → 2023 merger transfer), none within 24 months of each other, and no chained LLCs sharing an address or principal. This is the opposite of the <24-month waterfall pattern.

5. Pre-litigation transfer — NOT PRESENT.
The inventor assignments (2017-02-09) post-date the first suits (Teva notice Sept 2016; suit filed Nov 2016, D.N.J. 2:16-cv-07721) and the patent did not issue until 2017-07-18. The 2023 Indivior transfer post-dates the Teva/Perrigo litigation entirely. No assignment sits within 6 months before a first infringement suit naming the '226 patent.

6. Bankruptcy fire-sale — NOT PRESENT.
No Chapter 7/11 proceeding by Adapt, Emergent, Opiant, or Indivior. Opiant was solvent and publicly traded at its acquisition; Adapt sold at a premium.

7. Privateering — NOT PRESENT.
Adapt/Emergent and Opiant asserted the NARCAN patents directly and in their own names against genuine generic competitors (Teva, D.N.J.; Perrigo, D.N.J. filed 2018-10-25). There is no transfer of the patent to a third-party asserter acting on the owner's behalf. One adjacent item, which is not privateering but is worth recording: in January 2020 the New York Attorney General announced a settlement with Emergent after investigating a pre-acquisition Adapt contract with its nasal-spray device manufacturer that "may have had the effect of restricting" that manufacturer from supplying similar devices to would-be nalmefene competitors — an antitrust/supply-restriction matter, not a patent-transfer-to-NPE matter.

8. Defensive aggregator — NOT PRESENT.
The chain terminates at Indivior UK Limited and Emergent BioSolutions Ireland Ltd — commercial operating entities. It does not end at RPX, AST, LOT Network, Unified Patents, or OIN. The patent has not been neutralized.

Verdict

Operating-company assertion

Justification (2–3 sentences). The chain of title terminates in two public operating pharmaceutical companies — Indivior UK Limited (assignee of Opiant's interest per the 2023-06-14 recorded reassignment, following the 2023-03-02 Indivior/Opiant merger) and Emergent BioSolutions Ireland Ltd (successor to Adapt Pharma, acquired Oct 2018 for up to $735M) — and the original assignees, Adapt Pharma Ltd and Opiant Pharmaceuticals Inc., brought NARCAN® Nasal Spray (NDA 208411, FDA-approved 2015-11-18) to market, so the asserted claims read on a real, shipped product. The only patent assertions in the record are Hatch-Waxman ANDA suits against actual generic competitors Teva (2016 / 2019) and Perrigo (2018-10-25) in D.N.J., filed in the owners' own names with no NPE intermediary. The single NPE in this file, Nalox-1 Pharmaceuticals, LLC (Burford-funded, 15 IPR petitions filed ~2019-02-19), is the challenger, not a link in the ownership chain — which is the inverse of the pattern under investigation.

Confidence: High on the verdict (operating-company assertion). Low on the evidentiary completeness of the assignment timeline itself, because reel/frame numbers and correspondents were not retrievable with the tools available to me. Signal 3 (repeat correspondent) is therefore unresolved, not negative.

Verify at: USPTO Assignment Center — https://assignmentcenter.uspto.gov/ (search patent number 9707226); mirrored at https://assignment.uspto.gov/patent/index.html. Cross-reference Google Patents legal events at https://patents.google.com/patent/US9707226/en (shows the 2017-02-09 Adapt/Opiant inventor reassignments and the 2023-06-14 Indivior UK reassignment, without reel/frame fields). Also confirm the outstanding gap: whether a recorded assignment or name-change documents Adapt Pharma Limited → Emergent BioSolutions Ireland Ltd, and the reel/frame behind the LightLake→Opiant change of name (Reel/Frame 035328/0599, per the patent family's own joint-research-agreement statement).

I'll research this patent and its prior-art citations. Let me start with targeted searches.

I found key leads. Let me get the specific "References Cited" section from the patent's front page (as reproduced in the litigation filing).

Let me get the complete front-page reference list from the '226 patent itself.

Prior-Art Analysis — US 9,707,226 B2 ("Nasal drug products and methods of their use")

0. Scope, method, and an important caveat up front

I researched this via public patent/litigation sources (Google Patents, Espacenet, USPTO PTAB filings and district-court records surfaced through web search). Two honest limitations must be stated before any § 102 mapping:

1. I could not retrieve the complete, verbatim front‑page "References Cited" table of US 9,707,226 B2 itself. The Google Patents full text supplied in the prompt omits the citation table, and my web searches returned the '226 citation list only in truncated form (from a district-court complaint that reproduces the '226 front page). Where a reference below comes from the sibling patents in the same family (US 9,468,747; US 9,629,965; US 9,775,838; US 10,085,937) rather than from a directly verified '226 page, I flag it.
2. A front-page citation is not necessarily an anticipation reference. Most of what appears under "References Cited" was considered by the examiner in § 102/§ 103 contexts; anticipation requires that every limitation of a claim be disclosed in a single reference (plus enablement). I note below where the cited art does not reach a full claim.

1. Patent identification (verified)

Family lineage: the '226 is a continuation in the original Lightlake Therapeutics naloxone-nasal-spray family, and it claims priority through US 14/659,472 (issued as US 9,211,253) and US 14/942,344 (issued as US 9,480,644). It is a sibling of US 9,468,747, US 9,561,177, US 9,629,965, US 9,775,838 and US 10,085,937, all sharing the same 2014-03-14 specification. The '226 was not among the patents taken to IPR (Nalox‑1's petitions targeted the '253, '747, '965, '177 and '838); it was asserted in district court against Teva's 2 mg ANDA (D.N.J., Adapt Pharma Operations Ltd. v. Teva, 2:18-cv-05752).

2. References cited on the face of the '226 patent (as reproduced in the litigation record)

The complaint in Adapt Pharma Operations Ltd. v. Teva reproduces the '226 front page. Directly verified from that reproduction:

U.S. Patent Documents (verified, partial):

• US 2016/0008277 A1 — Crystal et al. — published 2016-01-14 — class A61K 9/0043 (nasal drug delivery).

Foreign Patent Documents (verified, complete as reproduced):

Non-patent literature (verified, partial — the complaint excerpt truncates the list):

• Ashton H. et al., "Best evidence topic report. Intranasal naloxone in suspected opioid overdose," Emerg Med J 23(3):221–23 (Mar. 2006).
• Bailey A.M. et al., "Naloxone for opioid overdose prevention: pharmacists' role in community-based practice settings," Ann. Pharmacother 48(5):601–06 (May 2014).
• Barton E.D. et al., "Efficacy of intranasal naloxone as a needleless alternative for treatment of opioid overdose in the prehospital setting," J Emerg Med 29(3):265–71 (Oct. 2005).
• Barton E.D. et al., "Intranasal administration of naloxone by paramedics," Prehosp Emerg Care 6(1):54 ff. (2002).

Additional U.S. references appearing on the closely-related sibling patents (US 9,468,747; US 9,629,965; US 10,085,937 — same specification/family; likely but not directly verified for the '226):
US 4,181,726 (Bernstein, 1980); US 4,464,378 (Hussain, 1984); US 4,987,136 (Kreek et al., 1991); US 5,866,154 (Bahal et al., 1999); US 7,977,376 (Singh et al., 2011); US 9,192,570 (Wyse et al., 2015); US 9,211,253 (Crystal et al., 2015); US 9,468,747 (Crystal et al., 2016); US 9,480,644 (Crystal et al., 2016); US 2003/0077300 (Wermeling); US 2006/0099447 (Merkus); US 2006/0120967 (Namburi); US 2009/0017102 (Stinchcomb); US 2010/0113495 (Wermeling); US 2010/0168147 (Chapleo); US 2010/0331354 (Wermeling); US 2011/0046172 (Chapleo); US 2012/0270895 (Wermeling); US 2013/0023825 (Edwards); US 2015/0174061 (Wyse); US 2015/0258019 (Crystal); US 2016/0008277 (Crystal).

3. Reference-by-reference description and § 102 potential

Note on the '226's § 102 window: the effective priority date is 2014-03-14. Anything published after that date is generally not prior art under § 102(a)/(b) unless relied on under § 102(e) for an earlier effective filing. This is critical for several WO documents listed above and for the Crystal‑et‑al. family publications.

A. U.S. patent documents

US 4,464,378 (Hussain) — granted 1984 (filed ~1981) — Method for eliciting an analgesic or narcotic antagonist response. Discloses intranasal administration of naloxone to elicit a narcotic-antagonist response. This is expressly acknowledged in the '226 specification.

• § 102 potential: Could potentially anticipate only a very broad method-of-treatment claim ("nasally administering naloxone to reverse narcotic depression"). It does not disclose a pre-primed single-use device, ~100 µL fill, 4% w/v concentration, BZK, an isotonicity agent range, a stabilizing agent, pH 3.5–5.5, or the plume/ovality characteristics. It cannot anticipate any '226 claim that recites the device or the specific BZK-containing formulation.

US 4,181,726 (Bernstein, 1980) — listed on the sibling patents; class 424/260. I could not verify its disclosure content in this session, so I will not characterize it. (Flag: unverified.)

US 4,987,136 (Kreek et al., 1991) — cited in the '226 specification as disclosing "other useful opioid receptor antagonists." Relates to opioid-antagonist compounds/methods.

• § 102 potential: Anticipates at most a claim to use of an opioid antagonist; does not touch the device/formulation/spray limitations. Not an anticipation reference for the '226 independent claims.

US 5,866,154 (Bahal et al., 1999) — aqueous nasal formulation. In the family IPRs it was relied on for the stabilizing-agent (e.g., disodium edetate/EDTA) element.

• § 102 potential: Discloses a nasal formulation with a chelating/stabilizing agent, but not naloxone at the claimed dose, not BZK at 0.005–0.015% (w/v), not the pre-primed 100 µL device. Anticipation is not made out; it is an obviousness reference for the "stabilizing agent" limitation only.

US 7,977,376 (Singh et al., 2011) — listed on sibling patents; I could not verify its subject matter with confidence. (Flag: unverified.)

US 9,192,570 (Wyse et al., 2015) — Intranasal pharmaceutical dosage forms comprising naloxone. This is the single most substantively important cited reference for the family. Critically, Wyse teaches that benzalkonium chloride degrades naloxone and states that while other preservatives "were acceptable," BZK "was not, due to increased observed degradation" (col. 27, ll. 43–44, as quoted in the Federal Circuit dissent in Adapt Pharma Operations v. Teva, No. 20-2106, Feb. 10, 2022).

• § 102 potential: Wyse discloses intranasal naloxone dosage forms, so it is relevant to claims reciting nasal naloxone delivery. But because it teaches away from BZK, it cannot anticipate the '226 claims that require BZK (or any claim whose inventive core is the BZK-containing stable formulation). Its role is as the primary § 103 reference, not a § 102 anticipant.

US 9,211,253; US 9,468,747; US 9,480,644 (Crystal et al.) and US 2015/0258019 A1; US 2016/0008277 A1 (Crystal et al.) — these are same-family, commonly-owned documents sharing the 2014-03-14 priority.

• § 102 potential: None. They are not "prior art" to the '226 because they share (or post-date) the '226's effective filing date; their appearance on the '226 face reflects related-application citation practice, not anticipatory art.

US 2003/0077300 A1 (Wermeling, 2003); US 2010/0113495 A1 (Wermeling, 2010); US 2010/0331354 A1 (Wermeling, 2010); US 2012/0270895 A1 (Wermeling, 2012) — Wermeling's intranasal naloxone work (dosing, pharmacokinetics, opioid-harm-reduction).

• § 102 potential: Relevant to method-of-treatment and dose limitations (intranasal naloxone to reverse opioid overdose). They do not disclose the BZK content, the 0.2–1.2 mg isotonicity-agent range, or the pre-primed 100 µL single-use device; no full-claim anticipation.

US 2006/0120967 A1 (Namburi, 2006) — nasal formulation technology (unverified specifics).
US 2009/0017102 A1 (Stinchcomb, 2009) — transdermal/transmucosal delivery.
US 2010/0168147 A1 (Chapleo, 2010); US 2011/0046172 A1 (Chapleo, 2011) — opioid-antagonist formulations (naltrexone/naloxone class).
US 2013/0023825 A1 (Edwards, 2013) — nasal drug-delivery device (spray).
US 2006/0099447 A1 (Merkus, 2006) — nasal delivery/absorption-enhancer chemistry (cyclodextrin-type).

• § 102 potential: These are individually background/obviousness art. Each touches a sub-element (device, excipient, or antagonist class) but none discloses the full combination; none anticipates an '226 independent claim.

B. Foreign patent documents (selected)

WO 1982/003768 (Hussain, 1982-11-11) — expressly discussed in the '226 specification: a composition containing 1 mg naloxone HCl per 0.1 mL (i.e., 1% w/v) for nasal administration.

• § 102 potential: Discloses nasal naloxone for narcotic-induced respiratory depression, but at 1% w/v, not the claimed "at least about 4% (w/v)" / 4 mg-per-100 µL concentration, and without BZK or a pre-primed device claim structure. It cannot anticipate the '226 concentration/device claims; it is dose/route art.

WO 2000/062757 (Davies, 2000-10) — intranasal naloxone formulations for overdose reversal; used by Teva in the district court as an obviousness reference (with Kerr and Bahal).

• § 102 potential: Relevant to nasal naloxone formulation/dose, not to the BZK-preserved, specifically-titrated 100 µL pre-primed product. § 103 reference.

WO 2012/156317 (2012-11); WO 2014/016653 (2014-01) — nasal naloxone/opioid-antagonist delivery references.

• § 102 potential: General nasal-naloxone/formulation art; do not disclose the full '226 combination.

WO 2015/095644; WO 2015/136373; WO 2016/007729 — these published after the 2014-03-14 priority date. WO 2015/136373 is the PCT counterpart of the same Lightlake family and WO 2016/007729 is the sibling "co-packaged drug products" application; neither is prior art to the '226.

• § 102 potential: None (post-priority / same-family).

The remaining WO documents (1998–2012) are nasal, nasal-device, or formulation background art; individually none disclose the whole device + BZK formulation + spray-geometry combination.

4. The most relevant prior art in the substantive sense

Because front-page citations understate the art actually used, the genuinely most-relevant prior art for the '226's subject matter is the art developed in the family's IPRs and the Adapt v. Teva litigation:

• US 9,192,570 (Wyse) — intranasal naloxone dosage forms; teaches away from BZK.
• Wang (IPR2019-00685, Nalox-1 Ex. 1008) — nasal spray, single/multi-dose, 20–200 µL.
• WO 2000/062757 (Davies) — intranasal naloxone for overdose.
• Kerr et al. (2009), Randomized controlled trial comparing intranasal and intramuscular naloxone (Addiction) — intranasal naloxone dosing.
• US 5,866,154 (Bahal) — EDTA/stabilizing agent.
• Djupesland (2013), Nasal drug delivery devices (Drug Deliv. & Transl. Res. 3:42–62) — single/bi-dose, pre-primed spray devices.
• Handbook of Pharmaceutical Excipients (6th ed., 2009) — excipient properties.
• Kushwaha et al. (2011), Advances in nasal trans-mucosal drug delivery.
• Additional: Strang, Kulkarni (2012), Grassin-Delyle (2012), Barton (2005), Dowling (2008), Wermeling (2013), Kublik & Vidgren (1998), Kundoor & Dalby (2011).

Outcome: The PTAB (Final Written Decisions, Aug. 21, 2020, in IPR2019-00685/-00688/-00694) and the district court found the family claims not invalid over these combinations; the Federal Circuit reversed in part (2–1) in Adapt Pharma Operations Ltd. v. Teva, No. 20-2106 (Fed. Cir. Feb. 10, 2022), finding claims obvious — with a vigorous dissent arguing the majority relied on hindsight and ignored that the prior art taught away from BZK. (This tension is the central § 103 dispute over the family.)

5. Bottom-line § 102 conclusions

No single cited reference discloses all limitations of the '226's principal independent claims — i.e., a single-use, pre-primed nasal device delivering ~100 µL of an aqueous solution of ~2/4 mg naloxone HCl, with an isotonicity agent, ~0.005–0.015% (w/v) benzalkonium chloride, a stabilizing agent (e.g., disodium edetate), and pH 3.5–5.5, optionally with defined plume/ovality and droplet-size characteristics. The cited art was therefore deployed as § 103 combinations, not § 102 anticipations.

Caveats to keep in mind

• I was unable to obtain the '226's exact granted claim set in this session; the claim-limitation mapping above is drawn from the specification text supplied, the sibling patents, and the litigation pleadings, and is functional rather than claim-number-specific. To give you a claim-numbered § 102 chart, I would need the granted claims of US 9,707,226 (USPTO Patent Public Search / PatentCenter) — say the word and I'll work from that document directly.
• Several front-page entries (Bernstein '726; Singh '376; Namburi '967; Merkus '447; Stinchcomb '102) are listed but not verified here; I did not want to fabricate their contents.
• Priority/filing dates for the WO documents are given to the month; treat exact days as approximate.

Grounding sources: Google Patents US9707226B2; Espacenet bibliographic record for US9707226 (B2); Adapt Pharma Operations Ltd. v. Teva Pharmaceuticals USA, Inc., D.N.J. 2:18-cv-05752 complaint (courtlistener.com); Emergent BioSolutions/Opiant SEC disclosures; Nalox‑1 IPR2019-00685/-00694 exhibits (docketalarm.com, ptacts.uspto.gov); Fed. Cir. No. 20-2106 opinion (Feb. 10, 2022).

I'll analyze the prior art references associated with US 9,707,226 and their bearing on obviousness. Let me first verify the key references.

Let me pull the actual claims of the '226 patent and the references cited on its face.

Let me get the full claim set of the '226 patent and the references cited on its face.

Obviousness Analysis — U.S. Patent No. 9,707,226 B2 ("Nasal drug products and methods of their use")

0. Sourcing note

I have treated the Google Patents page for US 9,707,226 (https://patents.google.com/patent/US9707226/en) as the authoritative document. The Prior Art section of that page supplies the following express references: prior-art keywords patient, naloxone, less, spray, mist; U.S. Pat. No. 4,464,378 (Hussain); WO 82/03768 (Hussain); Dowling et al., Ther Drug Monit 30(4) (2008); Kreek et al., U.S. Pat. No. 4,987,136; the MAD™ Nasal atomizer (Wolfe Tory) used with injectable naloxone (1 mg/mL); the Aptar/Pfeiffer UDS UnitDose and BDS BiDose single-/bi-dose devices and BD Accuspray; and the commercial nasal products Imitrex, Zomig and FluMist, which are on the page as evidence of the state of the device art.

Because the page's own prior-art discussion is thin relative to the record developed around this patent family, I supplement it with references that are confirmed in the public record as prior art to the same family (see §3). I flag explicitly where I am relying on the litigation/PTAB record rather than on the page. Two housekeeping points:

• The patent's stated priority date is 2014-03-14; the application was filed 2017-02-09, claiming priority via US 14/659,472 (→ US 9,211,253) and US 14/942,344 (→ US 9,480,644). The critical date is therefore no later than 2014-03-14, and possibly 2015-03-16 if the provisional priority fails (a point the IPR petitioners contested).
• I am not aware of an IPR petition filed specifically against the '226 patent. The Nalox-1 petitions (IPR2019-00685 through -00699) targeted the '253, '747, '177, '965 and '838 patents. The '226 was asserted in the Teva 2 mg ANDA litigation in D.N.J. (the litigation link on the page points to case 2:18-cv-05752). I do not have a verified final outcome for the '226 specifically, and I do not assert one below.

1. Legal framework

Under 35 U.S.C. § 103 and Graham v. John Deere Co., 383 U.S. 1 (1966), the inquiry is: (a) scope and content of the prior art; (b) differences between the prior art and the claims; (c) the level of ordinary skill; and (d) objective indicia. Under KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007), a combination is obvious where the improvement is the product of "ordinary creativity," where a finite number of identified, predictable solutions exist ("obvious to try"), or where the prior art teaches that a known technique is available and would predictably improve the art. Critically for the formulation and device claims here, KSR also authorizes reliance on "design incentives and other market forces," including an FDA-identified unmet need, as motivation to combine. In re Kao, 639 F.3d 1057 (Fed. Cir. 2011), governs PK-parameter limitations ("result-effective variables").

The POSA is best characterized as a formulator with a Ph.D. or equivalent and several years' experience in nasal/transmucosal drug delivery, working as part of a team including a device engineer — the definition used in the IPR record and accepted in the litigation.

2. The claims at issue

The '226 patent issued with 101 claims across three statutory classes (method, device/product-by-use, and article/mist). The commercially relevant and analytically representative claims are:

Claim 1 is the fulcrum. Note that it recites no pH range, no stabilizer, no specific tonicity agent, and no droplet/plume limitation — a considerably broader claim than the 4 mg claims held invalid in Adapt Pharma Operations Ltd. v. Teva Pharms. USA, Inc., No. 20-2106 (Fed. Cir. Feb. 10, 2022) (the '747 Patent's claim 1, which required the acid/pH, isotonicity agent, preservative and stabilizing agent together).

3. The prior art

3.1 References appearing in the page's Prior Art section

Three admissions within the page itself are unusually damaging and should be treated as applicant-admitted prior art in district court (cf. Qualcomm Inc. v. Apple Inc., 24 F.4th 1367 (Fed. Cir. 2022), which limits — but does not eliminate — the use of such admissions in IPR):

1. "The human nasal cavity has a volume of ~200–250 µL" and the 1 mL/nostril MAD protocol "is larger than that generally utilized," causing "loss of drug from the nasal cavity, due either to drainage into the nasopharynx or externally."
2. "Metered spray pumps … typically deliver 100 µL (25–200 µL) per spray, and they offer high reproducibility of the emitted dose and plume geometry in in vitro tests."
3. "Traditional spray pumps replace the emitted liquid with air, and preservatives are therefore required to prevent contamination."

3.2 Family-level prior art confirmed in the public record

• Wyse, U.S. Pat. No. 9,192,570 — intranasal naloxone; disclosed NaCl, and the use of preservatives; expressly identifies BZK as producing an "additional degradant" and states that whereas other preservatives "were acceptable," BZK "was not, due to increased observed degradation" (col. 27). Identified in the litigation as the closest prior art. See https://cafc.uscourts.gov/opinions-orders/20-2106.OPINION.2-10-2022_1906561.pdf
• Wang, CN 1575795 — naloxone nasal spray comprising naloxone HCl, "an osmotic pressure regulator, a preservative, a penetration enhancer and water"; Example 1 uses NaCl and HCl to "a pH value of 3.8 ± 0.8"; claim 3 lists benzalkonium chloride among suitable preservatives; claimed single doses of 0.1–10 mg.
• Wermeling, U.S. Pat. No. 8,198,291 — intranasal opioid compositions delivered from a Pfeiffer UnitDose Second Generation device; the spray plume measured ovality ~1.1 (range 1.0–1.3) at 3 cm and ~1.1 at 5 cm. See Donovan Declaration, IPR2019-00685, Ex. 1002, https://www.docketalarm.com/cases/PTAB/IPR2019-00685/
• Kerr et al. (2009) — "Effect of Formulation Variables on the Nasal Permeability and Stability of Naloxone Intranasal Formulations" — teaches that BZK degrades naloxone, which is why the closest prior-art formulators abandoned it.
• Handbook of Pharmaceutical Excipients (HPE) — BZK is used in nasal/otic formulations at 0.002–0.02% w/v, including 0.01% w/v in small-volume dosage forms; NaCl as isotonicity agent; disodium edetate as chelating/stabilizing agent; HCl for pH adjustment.
• Djupesland; Bahal; Kushwaha; Strang; Kulkarni; Davies — nasal device geometry, permeation enhancers, and excipient selection.

4. Combination A — Wyse '570 + HPE + Djupesland / Aptar UDS-BDS literature

Most directly aimed at claims 1, 2, 4–12, 18, 24, 30–31, 35, 37 (and, with BZK subsumed, the 2 mg claims).

Where every element is found

• Pre-primed device adapted for nasal delivery, delivering 25–200 µL: Djupesland and the Aptar UDS/BDS literature disclose a single-dose, pre-primed spray device with reservoir/piston/swirl chamber delivering ~100 µL, expressly acknowledged in the '226 specification itself. Wyse discloses intranasal administration of naloxone from a spray device.
• Naloxone HCl ~2 mg: Wyse and WO 82/03768 together teach 1 mg/0.1 mL; Wyse contemplates higher doses to improve exposure. A 2 mg/100 µL dose is a 2-fold concentration/dose step within a disclosed range.
• Isotonicity agent: Wyse and Wang each disclose NaCl.
• BZK at 0.005–0.015% (w/v): HPE discloses BZK at 0.002–0.02% w/v in nasal formulations, with 0.01% as a standard preservative concentration; Wang lists BZK among suitable preservatives. 0.01% w/v = 0.01 mg/100 µL — squarely within the HPE range.

Motivation to combine (this is the strongest part of the case)

1. FDA-driven market force. As the Adapt opinion records, the FDA in 2012 publicly urged industry to "develop an intranasal naloxone product that could be FDA approved," and advised that a higher dose than the contemplated 2 mg could be used to approach the IM product's bioavailability. KSR expressly permits reliance on such an articulated regulatory/design incentive.
2. Known, documented shortcomings of the MAD Kit. The page itself recites the 1 mL-per-nostril volume exceeding the ~200–250 µL nasal cavity, causing drainage; the MAD system is also "not assembled and ready-to-use." Fixing a known, quantified defect is the paradigm motivation to modify.
3. Preservative necessity. The page admits that traditional pumps require preservatives, and that preservative-free operation requires a single-dose/sterile-filled device. So a POSA seeking an FDA-approvable, preservative-containing multi-dose or reusable nasal product is taught to include an antimicrobial preservative — and BZK is the most common nasal preservative (HPE).
4. Bioavailability gap. Dowling's 4% relative IN bioavailability is a known problem; BZK is a known cationic surfactant/permeation enhancer, and Wang discloses a "penetration enhancer" as a required component of a naloxone nasal spray. Adding BZK thus serves two independent, known functions (preservation and permeation enhancement) — a classic KSR "known technique, predictable result" situation.
5. Routine optimization of the remaining excipients. NaCl (tonicity), edetate (stabilizer/chelator) and HCl (pH) are the canonical nasal-formulation excipients; the HPE and Wang supply them; the district court in Adapt held that arriving at the claimed ranges for these "well-known" excipients "would have required no more than routine optimization," and the Federal Circuit affirmed.

5. Combination B — Wang (CN 1575795) + Djupesland + HPE + Bahal/Kushwaha

The ground the PTAB actually instituted on.

Wang is the single most on-point reference: a naloxone nasal spray containing naloxone HCl, an osmotic-pressure regulator (NaCl, 0.9 g/100 mL), a preservative (expressly including benzalkonium chloride), a penetration enhancer, and water, adjusted to pH 3.8 ± 0.8 with 0.1 mol/L HCl — i.e., every functional element of '226 claim 1, plus the acid/pH, plus the enhancer.

• Pre-primed single-dose device: Djupesland — and, per the Donovan Declaration, "Djupesland discloses single-use, pre-primed devices adapted for nasal delivery … by one actuation."
• 0.01% BZK: HPE supplies the 0.002–0.02% w/v range and the 0.01% figure; Bahal/Kushwaha supply enhancer selection and tolerance.
• 100 µL, 2 mg dose: nasally dictated by the ~200–250 µL cavity volume; Wang's claim 9 teaches single doses of 0.1–10 mg, squarely encompassing 2 mg.

Motivation: Wang establishes that a naloxone nasal spray with exactly this excipient architecture was known and operable; Djupesland establishes the pre-primed single-dose device; the POSA need only select within Wang's disclosed ranges (preservative at 0.01%, dose at 2 mg, volume at ~100 µL) — a finite, small set of predictable options. This is the strongest "obvious to try" formulation of the case.

6. Combination C — Hussain '378 / WO 82/03768 + Aptar UDS/BDS + Wermeling '291

Aimed at the device/mist claims (40–64) and the plume limitations (21, 43–47).

• Hussain's two references establish that intranasal naloxone at systemic-equivalent doses (including 1 mg/0.1 mL) was known as of 1982–1984 — long before the priority date.
• The Aptar UDS/BDS literature discloses the exact device architecture claimed as "pre-primed" with a reservoir, delivering ~100 µL, with reproducible plume geometry; the '226 specification admits this and even names the 125 µL fill used for Imitrex/Zomig.
• Wermeling '291 supplies the plume numbers: a Pfeiffer UnitDose Second Generation device produced ovality ~1.1 at 3 cm (1.0–1.3) and ~1.1 at 5 cm.

Motivation and mechanism: The ovality ratio and droplet-size distribution flow from the swirl chamber and actuator orifice — properties of the device, not of the naloxone molecule. The page itself concedes that "the particle size and plume geometry … depend on the properties of the pump, the formulation, the orifice of the actuator, and the force applied." A POSA who places a Hussain/Wang-type naloxone solution into a Pfeiffer/Aptar UDS device — which the page states was already done for sumatriptan, zolmitriptan and influenza vaccine — will inherently obtain a round plume with ovality ratio <2.0 and a DSD in which few droplets are <10 µm, because that is the documented performance of that device. Under In re Oelrich and In re Best, a limitation that is the necessary and inherent result of practising a disclosed combination cannot confer patentability. That proportionality argument is reinforced by the page's own admission that a POSA must "avoid" droplets <10 µm because they are inhaled to the lung — an established safety-oriented design constraint (the page ties it to BZK's mucociliary toxicity), which supplies the motivation to select a device/nozzle that keeps the <10 µm fraction low.

7. The PK limitations (claims 48 and 96–101)

Claims 48 and 96 are result-effective-variable claims. A geometric-mean Cmax ≥2.9 ng/mL and ≥40% bioavailability following a 2 mg IN dose in a 100 µL spray are the pharmacokinetic consequence of (a) the dose, (b) the low pH/buffered aqueous vehicle, and (c) the BZK-facilitated permeation — all of which the prior art supplies. Under In re Kao and In re Papesch, "obvious to try" applies with particular force "where the prior art gave either no indication of which parameters were critical or no direction as to which of many possible choices is likely to be successful." Here the art did give direction: the FDA wanted bioavailability approaching the IM product, and the art identified concentration, low pH, and permeation enhancer as the levers. I note, however, that I cannot verify from the sources retrieved the precise prior-art IN Cmax values for a 2 mg dose, so the Cmax limitation is the one place a genuine factual dispute could exist.

8. The counter-case — and why it is weaker for the '226 than it was for the '747

The patent owner's strongest non-obviousness arguments are well documented and should not be dismissed:

1. Teaching away. Wyse '570 states BZK "was not [acceptable], due to increased observed degradation" of naloxone. The PTAB found this persuasive: in IPR2019-00698 (the '838 Patent) the Board denied institution because "the prior art teaches away from the claimed invention." See https://www.docketalarm.com/cases/PTAB/IPR2019-00698/. The Board likewise denied the Wyse-based petitions against the '177 and '838 patents, and instituted on the '253/'747/'965 only as to claims not limited to BZK specifically. See D.N.J. 2:16-cv-07721, ECF 283, at 1–3, https://storage.courtlistener.com/recap/gov.uscourts.njd.[340302](/patent/340302)/gov.uscourts.njd.340302.283.0_1.pdf
2. No articulated motivation. Judge Newman's dissent in Adapt called the majority's reconstruction of the formulation from scattered references "a classical example of judicial hindsight."
3. Objective indicia. Alleged unexpected results (a 56% bioavailability gain over the Wyse-derived AntiOp formulation), failure of others (Amphastar, Mundipharma, AntiOp), long-felt need, copying by ANDA filers, and commercial success.

Why these may not save the '226 claims:

• The Federal Circuit affirmed the contrary teaching-away finding for the 4 mg method claims, holding that a single report of degradation at a BZK concentration ~50–200× higher than the claimed one did not discourage a POSA, given that 0.01% BZK was "commonly used in intranasal formulations." That reasoning applies at least as strongly to a 0.005–0.015% range.
• The "unexpected results" case was rejected because BZK was a known permeation enhancer and the bioavailability increase was therefore expected.
• The long-felt-need error was held harmless because the need "began just three years before the priority date" and could not overcome "the strong case of obviousness … in view of the plethora of prior art."
• Claim 1 of the '226 is broader than the claim held invalid. It omits the acid/pH limitation, the stabilizer, and the specified isotonicity agent. Broader claims are a fortiori more vulnerable to the same combination. If claim 1 of the '747 was obvious over Wyse + HPE + Djupesland/Kerr, claim 1 of the '226 is obvious over Wang + HPE + Djupesland, since Wang supplies far more of the claim than Wyse did.
• One nuance in the patent owner's favor: the Adapt court's reasoning leaned on the FDA having encouraged a higher dose than 2 mg. A skilled advocate could argue that a 2 mg/100 µL product runs against that specific regulatory signal. That is a factual argument about the weight of the FDA evidence, not a legal bar, and it is undercut by WO 82/03768 (1 mg/0.1 mL), Hussain, and the standard 0.4 mg IM starting dose the art sought to mimic at higher IN doses.

9. Bottom line

A prima facie case of obviousness under § 103 is made out against substantially all of the '226 claims, and the motivation to combine rests on grounds KSR expressly endorses: a documented, FDA-articulated need; a quantified defect in the prevailing MAD-Kit practice (drainage from an over-filled nasal cavity); a known device platform already used for nasal pharmaceuticals; and conventional, individually disclosed excipients whose selection requires no more than routine optimization. The principal viable rebuttals are (a) the Wyse teaching-away argument on BZK — which the PTAB credited for the '838 patent but the Federal Circuit rejected for the '747 patent — and (b) an argument that the FDA's higher-dose signal cuts against the specifically 2 mg '226 claims. Both are litigation positions, not legal bars.

Caveats I want to be explicit about: the Federal Circuit's Adapt invalidity holding is a holding on the '747/'177/'965/'838 claims, not on the '226; the '226's own asserted claims were litigated in the separate 2 mg ANDA case, whose outcome I have not verified; and I have not independently verified the numeric prior-art Cmax values relevant to claim 96. Everything in §3.1 is drawn from the page you designated; everything in §3.2 is drawn from the identified public-record sources and is labelled as such.