US 11241414

Summary of U.S. Patent No. 11,241,414 ("the '414 patent")

I searched for the specific patent number 11241414 (interpreted literally, no auto-correction). Below is the authoritative summary, cross-checked against the USPTO-issued patent text (the Google Patents/USPTO image copy), USPTO PTAB records, and third-party patent databases. A targeted search of CAFC 2026 dockets returned no CAFC appeal docketed in 2026 for this patent; details on the related pending proceedings are noted at the end.

Bibliographic data

Abstract

"The invention relates to pharmaceutical compositions comprising one or more benzodiazepine drugs for nasal administration, methods for producing and for using such compositions."

The specification is directed to dissolving benzodiazepines (particularly diazepam) in a non-aqueous carrier of vitamin E-type tocopherols/tocotrienols plus lower alcohols/glycols (particularly ethanol and benzyl alcohol), with an alkyl-glycoside absorption enhancer, to permit concentrated intranasal spray delivery — useful for rapid treatment/prevention of seizures (e.g., epilepsy, seizure clusters), with claimed benefits of fast onset, avoidance of first-pass metabolism, and no need for IV or rectal administration.

Independent claims — plain-language overview

Claim 1 (independent). A nasal-administration pharmaceutical solution that is closed-ended ("consisting of") and contains only:

1. Diazepam (or a pharmaceutically acceptable salt thereof);
2. One or more natural or synthetic tocopherols or tocotrienols (alone or combined) at 30% to 95% (w/w);
3. Ethanol and benzyl alcohol combined at 10% to 70% (w/w); and
4. n-Dodecyl beta-D-maltoside (an alkyl-glycoside penetration enhancer).

Because the claim uses "consisting of," no additional components are permitted beyond the enumerated diazepam, tocopherol/tocotrienol, the two alcohols, and the alkyl glycoside.

Claim 11 (independent). Identical scope to claim 1 in all respects, except that the tocopherol component is restricted to one or more natural or synthetic α-tocopherols (rather than the broader tocopherol/tocotrienol class), again at 30% to 95% (w/w), with ethanol + benzyl alcohol at 10%–70% (w/w), diazepam/salt, and n-dodecyl beta-D-maltoside, in a "consisting of" nasal solution.

Dependent claims (2–10 and 12–18) narrow the two independent claims by, for example: diazepam concentration of 1–20% (w/v) or 10–250 mg/mL (20–50 mg/mL in narrower claims); enumeration of specific tocopherol/tocotrienol species (claim 5); tightening the tocopherol amount to 45–85% and 60–75% (w/w); tightening the ethanol/benzyl alcohol combined amount to 15–55% and 25–40% (w/w); and claim 10, which specifies the solution consists of diazepam, vitamin E, ethanol, benzyl alcohol, and n-dodecyl beta-D-maltoside.

Litigation / PTAB / CAFC status (as of April 26, 2026)

• No CAFC 2026 docket for the '414 patent itself was found. The only Federal Circuit appeal identified in the record is Appeal No. 2021-1038, Neurelis, Inc. v. Aquestive Therapeutics, Inc., a Rule 36 affirmance (Oct. 7, 2021) of IPR2019-00451 — but that case concerned the parent patent 9,763,876, not the '414 patent.
• PTAB IPR2025-00465 (Padagis US LLC v. Neurelis Inc.), challenging claims 1–18 of the '414 patent as obvious over Gwozdz (WO 2009/120933) in view of Meezan (US 2006/0046962), is pending/instituted (Google Patents metadata: "Pending - Instituted"). The Board projected a final written decision by September 17, 2026, and the proceedings are active (stipulated schedule through June 2026); a CAFC appeal from that IPR could not yet exist as of the current date.
• District court (Hatch-Waxman) litigations involving the '414 patent are pending in the District of Delaware, e.g., Neurelis v. Padagis, 1:25-cv-00821 (filed July 2, 2025, asserting the '414 among related patents against generic VALTOCO ANDA filers) and Neurelis v. Lupin/Padagis, 1:26-cv-00261.

Notes on uncertainty

• The official USPTO front page (filed May 27, 2021; issued Feb. 8, 2022) was treated as authoritative; minor one-day variances in third-party databases (e.g., Unified Patents showing application date 2021-05-26 and grant date 2022-02-07) are data-entry discrepancies.
• Claim text quoted above was verified against the issued patent claims as reproduced by DrugPatentWatch and the USPTO PDF; the two independent claims are claims 1 and 11 of 18 total claims.
• Anticipated-expiration dates (2029-03-26 vs. 2029-03-27) vary slightly across databases; all sources agree the patent expires in late March 2029 subject to the terminal disclaimer.

Litigation involving U.S. Patent No. 11,241,414 (the "'414 patent")

Based on searches of PTAB records, D. Del. dockets (PACER/Justia/CourtListener/Docket Alarm), and the litigation flags embedded in the Google Patents record for US11241414B2, the '414 patent is currently involved in the following proceedings. All are ANDA/Hatch-Waxman litigation over generic versions of Neurelis's VALTOCO® (diazepam nasal spray), plus one inter partes review.

Note on the Google Patents "litigation" flags: the metadata for the '414 patent lists IPR2025-00465, D. Del. 1:25-cv-00821, and D. Del. 1:26-cv-00261. The "Unified Patents" attribution shown beside the PTAB entry is a data-licensing credit, not the petitioner; the actual IPR petitioner is Padagis US LLC.

1. IPR2025-00465 – Padagis US LLC v. Neurelis, Inc. (PTAB)

• Petitioner: Padagis US LLC
• Patent owner: Neurelis, Inc.
• Jurisdiction: USPTO Patent Trial and Appeal Board
• Case number: IPR2025-00465
• Filed: January 17, 2025
• Institution: September 16, 2025 (trial instituted)
• Status: Pending — trial instituted; no final written decision yet (projected FWD due date reported as ~September 17, 2026). Neurelis filed a motion to strike and a request for discretionary denial; the Acting Director declined discretionary denial (decision designated informative on January 9, 2026), and the case was referred for a merits institution decision. The petition challenges claims 1–18 as obvious over Gwozdz (WO 2009/120933) in view of Meezan (US 2006/0046962), relying in part on collateral estoppel from IPR2019-00451 (which invalidated claims of related parent patent 8,895,546 / family member 9,763,876).
• Sources: ptacts.uspto.gov filings; ai-lab.exparte.com PTAB case page; jdsupra (informative-decision summary).

2. Neurelis, Inc. v. Padagis LLC et al., No. 1:24-cv-00562-MN (D. Del.) — "Padagis I"

• Plaintiff: Neurelis, Inc.
• Defendants: Padagis LLC; Padagis US LLC; Padagis Israel Pharmaceuticals Ltd. (Lupin entities are involved in the consolidated action)
• Jurisdiction: U.S. District Court for the District of Delaware (Judge Maryellen Noreika)
• Filed: May 8, 2024
• Patents asserted (per DrugPatentWatch/docket): includes the '414 patent (asserted claims 1–3, 5–13, 15–18), plus 8,895,546, 11,793,786, 12,268,664, 12,324,852, 12,337,061, and 12,521,400
• Status: Pending — this is the lead/consolidated ANDA case (Padagis ANDA No. 219320). The originally scheduled bench trial (Feb. 9, 2026) was moved; recent docket entries reflect a pretrial conference of Feb. 22, 2027 and a 5-day bench trial beginning March 1, 2027.
• Sources: drugpatentwatch.com litigation page; Docket Alarm docket 1:24-cv-00562; ai-lab.exparte.com complaint analysis.

3. Neurelis, Inc. v. Padagis LLC et al., No. 1:25-cv-00821-MN (D. Del.)

• Plaintiff: Neurelis, Inc.
• Defendants: Padagis LLC; Padagis US LLC; Padagis Israel Pharmaceuticals Ltd.; Lupin Inc.; Lupin Ltd.; Lupin Pharmaceuticals, Inc.
• Jurisdiction: D. Del. (Judge Noreika)
• Filed: July 2, 2025
• Patents asserted: '414 (claims 1–3, 5–13, 15–18 against Lupin), '786, and '664, arising from Padagis ANDA No. 219320 and Lupin ANDA No. 220394
• Status: Pending — consolidated with / associated to lead case 1:24-cv-00562-MN.
• Sources: Justia docket 1:2025cv00821; ai-lab.exparte.com complaint analysis.

4. Neurelis, Inc. v. Amneal Pharmaceuticals LLC et al., No. 1:26-cv-00261-MN (D. Del.)

• Plaintiff: Neurelis, Inc.
• Defendants: Amneal Pharmaceuticals LLC et al.
• Jurisdiction: D. Del.
• Filed: Complaint docketed March 11, 2026 (summons issued March 11, 2026)
• Patents asserted: includes the '414 patent (the complaint analysis details '414 claim 1 infringement allegations against Amneal's ANDA No. 219109 products), plus other family members such as the '852 and '061 patents
• Status: Pending — consolidated with lead case 1:24-cv-00562-MN (per the related-case list in the later Strides complaint).
• Sources: ai-lab.exparte.com complaint analysis (1:26-cv-00261); open-public-records.com D. Del. records.

Related consolidated ANDA actions (same patent family; likely asserting the '414 patent)

The Strides Pharma complaint (below) identifies the following as related actions consolidated under lead case 1:24-cv-00562-MN: 1:25-cv-01228-MN (Neurelis v. Padagis LLC), 1:25-cv-01443-MN (Neurelis v. Lupin Inc.), 1:26-cv-00258-MN (Neurelis v. Lupin Inc.), 1:26-cv-00401-MN (Neurelis v. Padagis LLC), and 1:26-cv-00947-MN (Neurelis v. Strides Pharma Global PTE Ltd. and Strides Pharma Inc., ANDA No. 221329). The Strides complaint expressly asserts the '414 patent among the "Asserted Patents." One caveat: that docket shows a filing date of July 31, 2026, which is after your stated current date of April 26, 2026 — the retrieved records appear to include updates later than the stated "today," and I am reporting them as the sources show.

Also relevant (not directly against the '414 patent)

• IPR2019-00451 invalidated claims of related family patent 9,763,876 (the "'876 patent"), and that decision (affirmed by the Federal Circuit) is being used by Padagis as collateral estoppel in IPR2025-00465. It is not itself litigation on the '414 patent.

Bottom line

There is active litigation involving the '414 patent: one instituted IPR (IPR2025-00465, Padagis v. Neurelis, pending) and multiple consolidated Delaware ANDA cases filed by Neurelis against Padagis, Lupin, Amneal, and Strides (lead case 1:24-cv-00562-MN), all pending as of the most recent docket entries. No final judgments or final written decisions disposing of the '414 patent were located.

Sources cited above include: dockets.justia.com, courtlistener.com, docketalarm.com, drugpatentwatch.com, ai-lab.exparte.com, ptacts.uspto.gov, open-public-records.com, and the litigation flags on the Google Patents page for US11241414B2.

Proceedings overview

There is one AIA trial proceeding against US 11,241,414 — IPR2025-00465, Padagis US LLC v. Neurelis Inc. — and it is active (trial instituted on all claims 1–18, no Final Written Decision yet). The structured USPTO ODP block in the prompt shows "no AIA trial proceedings on file," which is a stale-ingest artifact: the USPTO's own PTACTS docket, DrugPatentWatch, and multiple law-firm reports confirm IPR2025-00465 was filed 2025-01-17 and instituted 2025-09-16. No claims of the '414 patent have been canceled, none have been sustained in a FWD, nothing has settled, and no institution has been denied. Bottom line for a defendant: the '414 patent is not hardened — it is mid-flight through a single-IPR challenge that was instituted on all 18 claims on the same Gwozdz + Meezan obviousness theory that already killed the near-identical claims of parent patent 9,763,876 in IPR2019-00451 (affirmed by the Federal Circuit). The Final Written Decision is due on or about 2026-09-17 — within days of today (2026-09-09).

IPR2025-00465 — Padagis US LLC v. Neurelis Inc.

• Type: Inter Partes Review
• Filed: 2025-01-17
• Status: "Trial Instituted" (per DrugPatentWatch and the Ex Parte/PTACTS docket) — institution granted on all challenged claims; trial phase ongoing. No FWD issued as of today (2026-09-09).
• Judge panel: Grace Karaffa Obermann, Annette R. Reimers, and Timothy G. Majors (Majors authored the panel's 2026-03-20 rehearing decision; the same panel sits across the three related Padagis IPRs). Counsel: Polsinelli (Padagis, James Murphy/Corey Casey); McDermott Will & Emery and DLA Piper (Neurelis).
• Petition grounds: One ground — all claims 1–18 alleged obvious under § 103 over Gwozdz (WO 2009/120933) in view of Meezan (US 2006/0046962). Padagis argued Gwozdz discloses everything except the claimed alkyl glycoside (n-dodecyl β-D-maltoside), which Meezan teaches as an intranasal absorption enhancer, and invoked collateral estoppel from the FWD in IPR2019-00451 (the '876 parent patent), contending the '414 claims are "not materially different" from claims already held obvious and that Neurelis is precluded from relitigating (i) the '558 provisional's lack of written-description support for the alkyl-glycoside limitation, (ii) Gwozdz's entitlement to its 2008 provisional priority date, and (iii) the motivation to combine Gwozdz with Meezan.
• Institution decision: Instituted — 2025-09-16 (DrugPatentWatch decision date; Ex Parte docket shows "Institution 09/16/25," outcome "Instituted"). Institution followed an unusual Director-review detour: Neurelis sought discretionary (Fintiv) denial based on the D. Del. trial set for 2026-02-09, but Acting Director Coke Morgan Stewart declined discretionary denial and referred the petitions to the Board (Padagis US LLC v. Neurelis, Inc., IPR2025-00465, Paper 12 (July 16, 2025)), reasoning that the examiner's later priority-date finding "directly contradicts" the Board's IPR2019-00451 determination that the family is not entitled to the '558 provisional's date, raising "concerns of material error" warranting Office review under Advanced Bionics; that decision was designated informative on 2026-01-09 by Director John Squires. On referral, the Board found the allegedly narrowed '414 claims "did not find adequate written description support in the relevant priority applications or avoid Gwozdz as prior art," and instituted on the merits.
• Final Written Decision: Not yet issued. Projected FWD due date: 2026-09-17 (stated in both the Acting Director's Paper 12 and the Jones Day write-up of the informative decision) — i.e., roughly the statutory one-year deadline from the 2025-09-16 institution.
• Settlement / termination: None. The parties are litigating the merits — Neurelis served a Patent Owner Response with the declaration of Dr. Marc Brown; Padagis served a reply with a supplemental declaration of Dr. Maureen Donovan (2026-03-17 deposition; reply declaration addressing n-dodecyl β-D-maltoside disclosure/motivation and POSITA definitions).
• Key procedural event (defensive gambit rejected): Neurelis moved for leave to petition for a certificate of correction adding a Joint Research Agreement disclosure — which would have triggered the pre-AIA § 103(c)(2)(C) safe harbor and eliminated Gwozdz from the sole ground, "essentially case dispositive across all three proceedings." The Board denied the motion (Paper 36, 2026-02-06) and denied rehearing (Paper 39, 2026-03-20), citing Neurelis's ~7-year delay (on notice since the 2019 '876 IPR), the absence of any good-faith allegation, and substantial prejudice because Padagis is "statutorily time-barred from filing another IPR petition against the challenged patents" that does not rely on Gwozdz.
• Appeal: None possible yet — no FWD, hence no Federal Circuit appeal of this proceeding. (The frequently-cited CAFC outcome, Neurelis v. Aquestive, Appeal No. 2021-1038, Rule 36 affirmance 2021-10-07, was an appeal of the '876 parent's IPR2019-00451, not of the '414 patent.)
• Defensive value: This proceeding cuts against a defendant seeking to invalidate the patent quickly — no claim has been canceled, and Neurelis has shown it will fight procedural skirmishes hard. But it cuts in favor of a defendant seeking leverage: the Board has already institution-stage rejected Neurelis's priority-date and written-description defenses on nearly identical claim language that the PTAB (and CAFC) previously found obvious over the same two references. A FWD invalidating claims 1–18 within days is a realistic, near-term scenario, and Padagis's § 315(e)(2) estoppel (once a FWD issues) will bind Padagis and its privies — not a stranger defendant.

Strategic summary

Claims status of the '414 patent (as of 2026-09-09): All 18 claims (1–18) are UNTESTED-by-FWD and none are CANCELED; all 18 are under active challenge in IPR2025-00465 on a single Gwozdz + Meezan obviousness ground. Because institution was granted on every claim, there is currently no claim of the '414 patent that has been either vindicated or eliminated by the PTAB. The closest analog is the family history: the '876 patent (a direct parent with near-identical claim language) had claims 1–16 and 24–36 held unpatentable over Gwozdz + Meezan in IPR2019-00451, affirmed by the Federal Circuit — and Padagis is pressing collateral estoppel to make that outcome stick on the '414. The Board's March 2026 rehearing decision expressly notes the '414/'786 applications were filed after the '876 FWD and while the CAFC appeal was pending, and that Neurelis's claim-narrowing did not escape Gwozdz — signaling the panel views the '414 claims as vulnerable.

Estoppel and remaining art: If a FWD issues against Padagis, § 315(e)(2) estoppel bars Padagis (and its privies — which likely includes the other ANDA defendants it coordinates with in the Delaware Hatch-Waxman cases, a fact pattern to investigate) from raising in district court or before the PTAB any ground it raised or reasonably could have raised — i.e., the Gwozdz/Meezan combination and closely related art. Conversely, a new, unrelated defendant is not estopped and could still run Gwozdz + Meezan (or better art) in its own IPR — subject to the § 315(b) one-year bar that starts running from service of that defendant's ANDA complaint. Practical caveat: the Board found Padagis itself is now time-barred from any new Gwozdz-independent petition, so the only pending validity vehicle on the '414 is this one ground — if the FWD somehow sustains the claims, there is no Padagis do-over.

Pattern signals: One petitioner (Padagis) filed a coordinated three-IPR campaign across the family — IPR2025-00464 ('546), IPR2025-00465 ('414), IPR2025-00466 ('786) — all instituted, all on the same Gwozdz-based ground, all before the same panel, with parallel Delaware ANDA litigation (1:24-cv-00562, 1:25-cv-00821, 1:26-cv-00261). That is a coordinated generic-entry attack on VALTOCO's patent thicket, not a scattered set of disputes. Neurelis has defended aggressively — Fintiv Director review (lost), a § 103(c) JRA certificate-of-correction maneuver (lost, with an adverse prejudice/estoppel-lite finding), and a § 255/Honeywell rehearing (lost) — suggesting it will appeal any adverse FWD to the Federal Circuit. Note: the "Unified Patents" label on the Google Patents litigation metadata is a data-attribution credit, not an indication that Unified Patents is the petitioner or is funding the IPR — Padagis US LLC is the real party.

Recommended next steps

1. Check for the FWD immediately — it is due on or about 2026-09-17. As of today (2026-09-09), no FWD has issued. Monitor PTAB E2E/PTACTS for IPR2025-00465 daily; if the Board follows its IPR2019-00451 reasoning (and the institution-stage priority-date findings), claims 1–18 are at real risk of cancellation. USPTO docket: https://ptacts.uspto.gov/ptacts/ (search IPR2025-00465). The Acting Director's referral decision is Paper 12 (2025-07-16) and the panel's rehearing denial is Paper 39 (2026-03-20).
2. If you are a defendant sued on the '414 patent today: do not assume the claims are dead — there is no estoppel-free FWD you can brandish yet. Instead, (a) file a motion to stay the district court case pending the imminent FWD (the Board itself noted stays have been granted in the related Delaware cases); (b) if you are not in privity with Padagis, preserve your own IPR options by calendarizing the § 315(b) one-year bar from service of the complaint against you; and (c) prepare for the post-FWD fork — if claims fall, move to dismiss or for summary judgment on the now-canceled claims; if claims survive, the Gwozdz/Meezan avenue is likely exhausted for Padagis-privity defendants and you must develop independent art.
3. Watch the parallel family IPRs (IPR2025-00464 on '546, IPR2025-00466 on '786) — they are on identical Gwozdz grounds before the same panel, so the '414 FWD will almost certainly move in lockstep with its siblings, and any CAFC appeal is likely to be consolidated.
4. If you are evaluating a license or settlement: Neurelis's defensive posture (Fintiv, JRA correction, rehearing) signals it values the patent highly, but its settlement leverage is weakest now, with a Gwozdz-based FWD days away and a prior CAFC affirmance of the same theory against the parent claims. Any settlement terms should be conditioned on, or priced against, the 2026-09-17 FWD.

Sources: Jones Day/PTAB Litigation Blog, "No Discretionary Denial Where Prior IPR Suggests Material Error By Office" (2026-03); USPTO PTACTS, Padagis v. Neurelis, IPR2025-00465, Paper 12 (Acting Director Stewart, 2025-07-16, informative) and Paper 39 (Board, 2026-03-20); Ex Parte docket for IPR2025-00465; DrugPatentWatch PTAB tables (status "Trial Instituted," decision 2025-09-16); paragraphfour.com VALTOCO litigation summary; District of Delaware dockets 1:24-cv-00562 and 1:25-cv-00821. The structured ODP "no PTAB activity" entry is superseded by these sources and should be treated as an ingest lag.

I'll research the full assignment record for US patent 11241414, starting with the USPTO assignment database and cross-referencing other sources.

Let me dig deeper into the USPTO assignment records, which are the primary source for this analysis.

Now I need the specific reel/frame records from the USPTO Assignment Center. Let me search for those.

I've hit the search limit for this session, so I'll now compile the analysis from the authoritative patent text (whose legal-events feed records the assignment history), the Unified Patents portal data, and the litigation dockets retrieved above. I'll flag clearly where reel/frame specifics could not be independently verified in this session rather than fabricate them.

Ownership-chain analysis: US Patent 11,241,414

Verification caveat up front: USPTO Assignment Center records exist for this patent (the events below are indexed on Google Patents' legal-events feed, reproduced in the authoritative patent text fetched 2026-09-09, and cross-confirmed by the Unified Patents portal). However, in this session I could not retrieve the individual reel/frame numbers or the correspondent attorneys of record from assignmentcenter.uspto.gov. Those fields are therefore marked "not verified in this session" rather than guessed. Search the patent number 11241414 at https://assignmentcenter.uspto.gov/ to confirm.

Inventors

Seven named inventors, all on the issued patent:

Employer at time of filing: The '414 patent is a 2021 continuation claiming priority to a 2008 provisional; the invention dates to the 2008–2009 era. The recorded 2021-12-13 assignment (inventors → Hale Biopharma Ventures, LLC) indicates the inventors' rights were held/formalized through Hale Biopharma Ventures, LLC (David F. Hale's company) before transfer to Neurelis. GoodIP's assignee profile lists Hale Biopharma Ventures as the portfolio owner for the earliest family filings (first publication 2008, including US 2009/0258865 A1).

Unusual pattern check: The seven inventors did not depart the operating company within 12 months of filing — rather, this is the inverse: the operating company (Neurelis) was the end-destination of the IP, with the inventors' chain cleaned up through their own holding vehicle on the eve of issuance. No portfolio fire-sale signal.

Original assignee

Neurelis, Inc. (San Diego, CA) is the assignee named on the issued patent (front page; also listed by DrugPatentWatch, Unified Patents "Parent Company," and the drugs.com Orange Book record).

• Product: Neurelis markets VALTOCO® (diazepam) nasal spray, FDA-approved January 2020 for acute treatment of seizure clusters in epilepsy patients; the '414 patent is listed in the Orange Book for VALTOCO (DrugPatentWatch).
• Line of business: Operating specialty pharmaceutical company (drug development/commercialization).
• Current status: Operating and actively litigating — plaintiff in Hatch-Waxman suits against generic ANDA filers Padagis and Lupin in the District of Delaware (1:25-cv-00821, filed 2025-07-02; 1:26-cv-00261), and patent owner defending IPR2025-00465 (Padagis v. Neurelis, instituted, FWD projected Sept. 2026).

Assignment timeline

Four recorded ownership/security events are indexed for this patent (per the Google Patents legal-events feed in the authoritative text and Unified Patents). Reel/frame numbers and correspondents not verified in this session — no fabrication attempted.

~2021 (executed) / 2021-08-06 (recorded) — Reel/frame: not verified

• Conveyance: Security Interest (grant of security interest — "SEE DOCUMENT FOR DETAILS")
• Assignor (grantor): Aegis Therapeutics, LLC and Neurelis, Inc.
• Assignee (secured party): Orbimed Royalty & Credit Opportunities III, LP
• Correspondent: not retrieved
• Context: Securitization / secured credit facility — OrbiMed (a healthcare investment firm) took a security interest over Neurelis and Aegis Therapeutics assets; this is royalty-linked lending, not a transfer of ownership. Aegis Therapeutics is the San Diego entity behind the Intravail® alkyl-glycoside enhancer technology referenced throughout the '414 specification, and is affiliated with Neurelis in this financing.

~2021 (executed) / 2021-12-13 (recorded) — Reel/frame: not verified

• Conveyance: Assignment of Assignors' Interest
• Assignor: David F. Hale, Andrew Loxley, Mark Mitchnick, Garry Thomas Gwozdz, Steve Cartt, Edward T. Maggio, David Medeiros (the seven inventors)
• Assignee: Hale Biopharma Ventures, LLC
• Correspondent: not retrieved
• Context: Chain-of-title cleanup — formalizes inventors' interests into the Hale-named holding vehicle while the '414 application was pending (filed 2021-05-27, granted 2022-02-08).

~2021 (executed) / 2021-12-13 (recorded) — Reel/frame: not verified

• Conveyance: Assignment of Assignors' Interest
• Assignor: Hale Biopharma Ventures, LLC
• Assignee: Neurelis, Inc.
• Correspondent: not retrieved
• Context: Internal reorg / consolidation into the operating company — recorded the same day as the inventors' assignment, placing full title in Neurelis so the patent could issue to the commercializing entity.

2024-11-14 (recorded) — Reel/frame: not verified

• Conveyance: Release by Secured Party
• Assignor (releasor): Orbimed Royalty & Credit Opportunities III, LP
• Assignee (released parties): Aegis Therapeutics, LLC and Neurelis, Inc.
• Correspondent: not retrieved
• Context: Release of the security interest — the OrbiMed credit facility lien was discharged; confirms OrbiMed never held ownership, only a financing encumbrance.

Timeline diagram

timeline
    title Ownership of US 11241414
    2008 : Provisional filed
    2009 : Family applications filed
         : Rights held via Hale Biopharma Ventures
    2021 : Neurelis continuation filed
         : OrbiMed takes security interest
         : Inventors assign to Hale Biopharma Ventures
         : Hale Biopharma Ventures assigns to Neurelis
    2022 : Patent issues to Neurelis
    2024 : OrbiMed releases security interest
    2025 : Neurelis sues Padagis and Lupin

NPE / troll-pattern signals

1. Shell-entity transfer — Not present as an NPE tell. The intermediate entity, Hale Biopharma Ventures, LLC, carries the "Ventures" suffix and is a Delaware-style LLC, which superficially matches the shell checklist. But the concrete evidence defeats the inference: (a) it is the namesake vehicle of named inventor David F. Hale; (b) the transfer into it (recorded 2021-12-13) and out of it to Neurelis (recorded 2021-12-13, same day) happened before issuance, as ordinary pre-issuance chain-of-title formalization; and (c) the chain terminates at Neurelis, Inc., an FDA-regulated operating company. There is no licensing-only LLC at the end of the chain.

2. Known asserter in the chain — Not present. Neurelis is not on Acacia/Marathon/IV/IPNav-type NPE lists; the asserter directories on the Unified Patents portal classify this as an operating-company portfolio (parent: Neurelis Inc.). OrbiMed is a healthcare investment/credit firm, not a patent NPE, and held only a security interest (2021-08-06), released 2024-11-14.

3. Repeat correspondent across the chain — Unclear / not determinable in this session. Correspondent names on the reel/frame records could not be retrieved within the available search budget. No finding either way.

4. Cascading transfers — Not present. The only back-to-back assignments (both recorded 2021-12-13) are a single two-step hop — inventors → Hale Biopharma Ventures → Neurelis — not chained LLC churn. They share a functional purpose (title consolidation into the issuer), not an obfuscation pattern.

5. Pre-litigation transfer — Not present. The assignments (recorded 2021-12-13) predate the first infringement suits naming this patent (Delaware 1:25-cv-00821, filed 2025-07-02) by more than three years, and predate issuance itself. Nothing was arranged on the eve of litigation.

6. Bankruptcy fire-sale — Not present. No bankruptcy proceeding involving Neurelis, Hale Biopharma Ventures, or Aegis Therapeutics appears in any retrieved record.

7. Privateering — Not present. Neurelis asserts the patent itself, in Hatch-Waxman suits against generic competitors (Padagis, Lupin), in defense of its own FDA-approved VALTOCO product. This is the opposite of an operating company hiding behind an NPE.

8. Defensive aggregator (anti-NPE) — Not present. The chain does not terminate at RPX, AST, LOT, Unified Patents, or OIN; it terminates at Neurelis, an operating company that asserts.

Verdict

Operating-company assertion — high confidence.

The chain is: seven inventors → Hale Biopharma Ventures, LLC (their own holding vehicle, recorded 2021-12-13) → Neurelis, Inc. (recorded 2021-12-13), with OrbiMed Royalty & Credit Opportunities III, LP holding only a security interest (recorded 2021-08-06) that was released (recorded 2024-11-14). The current assignee, Neurelis, ships the FDA-approved product VALTOCO embodying the claims and is asserting the '414 patent in Hatch-Waxman litigation against actual generic competitors Padagis and Lupin (D. Del. 1:25-cv-00821; 1:26-cv-00261), while defending IPR2025-00465 — the canonical profile of an operating-company assertion, with no NPE or troll signals present. The only "unclear" signal is correspondent-attorney recurrence, which could not be checked this session; verify reel/frame and correspondent fields at https://assignmentcenter.uspto.gov/ (search 11241414) to complete the record.

Prior-Art Analysis: U.S. Patent No. 11,241,414 B2 ("Administration of Benzodiazepine Compositions")

1. Patent-number verification (per your instruction not to auto-correct IDs)

Searches for the literal string 11241414 consistently returned US 11,241,414 B2, titled Administration of benzodiazepine compositions, assigned to Neurelis, Inc., invented by Steve Cartt, David Medeiros, Garry Thomas Gwozdz, Andrew Loxley, Mark Mitchnick, David F. Hale, and Edward T. Maggio. Issue date February 8, 2022 (application 17/332,800, filed May 27, 2021). I found no evidence that any search engine conflated it with a similar number (e.g., 11,241,414 is distinct from family members 8,895,546, 9,763,876, 11,793,786, 12,268,664, 12,324,852, 12,337,061, and 12,521,400). A direct USPTO PatFT full-text query was not accessible in this environment; the front-page "References Cited" list was therefore reconstructed from the official patent PDF replica (Google Patents/patentimages) and uspto.report's rendering of the grant, and cross-checked against the PTAB petition in IPR2025-00465.

Important caveat up front: I could not retrieve a complete, page-by-page reproduction of the entire "References Cited" section (the front page lists well over 70 U.S. patent documents, many of which are incorporated-by-reference drug-synthesis or formulation patents that the specification cites only for background). The analysis below covers every reference I could positively identify as appearing on the face of the '414 patent or as central to the pending IPR, and I flag where full bibliographic detail could not be verified.

2. Governing § 102 framework

Because the '414 patent is a continuation claiming priority to Provisional Application 61/040,558, filed March 28, 2008, and the claims are entitled to that priority date, the claims are examined under pre-AIA 35 U.S.C. § 102. Anticipation requires that a single reference disclose every element of the claimed invention, arranged as in the claim.

The two independent claims (claims 1 and 11) are closed ("consisting of") nasal pharmaceutical solutions requiring, together:

For a reference to "potentially anticipate," it must disclose all four of those limitations in a single nasal solution. As explained below, no single reference on the face of the '414 patent does so, which is consistent with the fact that the pending IPR challenges the claims only as obvious (pre-AIA § 103) over a combination of references.

3. References cited on the face of the '414 patent — most relevant to claims 1–18

A. Same-family / co-owned disclosures (not § 102 prior art, but on the face)

1. US 8,895,546 B2 — Cartt et al., "Administration of benzodiazepine compositions"

• Dates: Filed Mar. 27, 2009; issued Nov. 25, 2014.
• Description: The immediate parent patent in the '414 chain (Hale Biopharma Ventures, LLC). Discloses nasal pharmaceutical compositions of benzodiazepines (including diazepam) dissolved in tocopherol/tocotrienol carriers with alcohols/glycols, optionally with alkyl-glycoside absorption enhancers — the genus from which claims 1 and 11 of the '414 were narrowed.
• § 102 potential: None. It shares the identical priority date (Mar. 28, 2008) and the same inventive entity as the '414. It is not "by others" and does not precede the '414's effective filing date, so it cannot be § 102(a), (b), or (e) prior art. It is cited on the face and is relevant to obviousness-type double patenting (the '414 is subject to a terminal disclaimer) rather than anticipation.

2. US 2009/0258865 A1 — Cartt et al., published Oct. 15, 2009

• Description: The published parent application (12/413,439) of the same chain.
• § 102 potential: None — same priority date and inventive entity; not prior art to the continuation.

B. Benzodiazepine intranasal-delivery art (closest on the active-ingredient/route limitations)

3. US 2004/0176359 A1 — Wermeling, published Sept. 9, 2004 (also US 2006/0147386 A1 — Wermeling, published July 6, 2006)

• Description: Intranasal benzodiazepine (diazepam/midazolam) administration disclosures by a leading investigator in acute seizure delivery. These are genuine pre-2008, third-party publications squarely in the field.
• § 102 potential: Low. They address nasal benzodiazepine delivery generally but do not disclose the closed combination of diazepam + tocopherol/tocotrienol (30–95% w/w) + both ethanol and benzyl alcohol (10–70% combined) + n-dodecyl β-D-maltoside. They do not individually anticipate claims 1 or 11 (or their dependents).

4. US 9,192,570 B2 — Wyse et al., issued Nov. 24, 2015

• Description: Listed on the face of the '414 (per uspto.report). I could not independently verify its title or full disclosure in the available sources.
• § 102 potential: If it is a later-filed (post-2008) benzodiazepine-formulation patent, it postdates the '414's priority date and cannot be § 102(a)/(b) art; at most it could be § 102(e)/(g) art only if its own effective filing date precedes Mar. 28, 2008, which a 2015-issued patent normally would not. Flagged as requiring verification.

C. Alkyl-glycoside / "Intravail®" absorption-enhancer art (closest on the n-dodecyl β-D-maltoside limitation)

5. US 5,661,130 A — Meezan & Pillion, "Absorption enhancers for drug administration"

• Dates: Filed June 24, 1993; issued Aug. 26, 1997 (UAB Research Foundation).
• Description: The foundational patent for alkylsaccharide transmucosal absorption enhancers, expressly incorporated by reference in the '414 specification and identified (per PTAB filings in IPR2025-00465) as the root disclosure of Intravail®-type enhancers such as dodecyl maltoside and tetradecyl maltoside for intranasal delivery.
• § 102 potential: None for claims 1–18 standing alone. It discloses the enhancer class but not diazepam, the tocopherol/alcohol carrier system, or the closed formulation. It is classic secondary (obviousness) art for the enhancer limitation.

6. US 2006/0046962 A1 — Meezan et al., published Mar. 2, 2006 (Aegis Therapeutics lineage; this is the reference paired with Gwozdz in IPR2025-00465)

• Description: Discloses alkyl-glycoside (Intravail®) transmucosal absorption enhancement for nasally administered drugs. Used in the pending IPR petition as the secondary reference supplying the n-dodecyl β-D-maltoside/enhancer teaching.
• § 102 potential: None individually — it does not disclose the diazepam/tocopherol/ethanol+benzyl-alcohol closed solution. Relevant only to § 103 obviousness.

7. US 2006/0046969 A1 — Maggio, published Mar. 2, 2006 (and the related Aegis applications US 2006/0045868 A1 and US 2006/0045869 A1 — Meezan et al., published Mar. 2, 2006)

• Description: Alkylsaccharide/Intravail mucosal-delivery disclosures. Edward T. Maggio is a named inventor of both this art and the '414 patent; the examiner cited the series on the face.
• § 102 potential: None individually for the same reason as item 6. (Note: co-inventorship may affect availability under pre-AIA § 103(c)/102 if the references are "by the inventor," a fact-specific question I cannot resolve from the face record.)

8. US 2005/0276843 A1 — Quay et al., published Dec. 15, 2005

• Description: "Compositions and methods for enhanced mucosal delivery of parathyroid hormone" using Intravail alkyl glycosides (confirmed via the Unified Patents "Patent Art" listing for the '414 and the Aegis/Marina Biotech lineage). Third-party pre-2008 art on enhanced nasal absorption of small molecules with dodecyl maltoside.
• § 102 potential: None individually — different drug; supplies only the enhancer teaching for § 103.

D. Tocopherol / Vitamin E carrier art (closest on the 30–95% tocopherol limitation)

9. US 6,193,985 B1 — issued Feb. 27, 2001

• Description: Expressly incorporated by reference in the '414 specification as the source of the description of Vitamin E TPGS (tocophersolan). I could not independently verify the title from the available sources.
• § 102 potential: None for the closed claims — it concerns the tocopherol-derived excipient, not a diazepam nasal solution containing both ethanol and benzyl alcohol with dodecyl maltoside.

10. US 7,434,579 B2 — Young et al., issued Oct. 14, 2008 (with related application US 2003/0087820 A1 — Young et al., published May 8, 2003)

• Description: Cited among nanoparticulate/mucosal-delivery references on the face. Full title not verified in available sources.
• § 102 potential: None — these are nanoparticle-suspension/formulation references, and claims 1 and 11 require a fully dissolved, closed solution. They also (at least the B2) postdate the March 2008 priority date.

E. Incorporated-by-reference benzodiazepine synthesis patents (numerous; background only)

The specification incorporates by reference the classic manufacturing patents for each named benzodiazepine, and the examiner carried many onto the face: e.g., 3,102,116 (Aug. 1963), 3,109,843 (Nov. 1963), 3,136,815 (June 1964), 3,243,427 (Mar. 1966), 3,296,249 (Jan. 1967), 3,299,053 (Jan. 1967), 3,340,253 (Sept. 1967), 3,371,085 (Feb. 1968), 3,374,225 (Mar. 1968), 3,547,828 (Dec. 1970), 3,567,710 (Mar. 1971), 3,609,145 (Sept. 1971), 3,722,371 (Mar. 1973), 3,849,341 (Nov. 1974), 3,949,072 (Apr. 1976), 3,987,052 (Oct. 1976), 4,130,709 (Dec. 1978), 4,280,957 (July 1981), 4,397,951 (Aug. 1983), 4,440,675 (Apr. 1984), 4,608,278 (Aug. 1986), 4,657,904 (Apr. 1987), 4,690,952 (Sept. 1987), 4,748,158 (May 1988), 4,826,689 (May 1989), 4,868,289 (Sept. 1989), 4,921,838 (May 1990), 4,977,456 (Nov. 1990), 4,997,454 (Mar. 1991), 5,091,188 (Feb. 1992), and continuing through the 1990s (e.g., 5,831,089, midazolam synthesis).

• Description: These are diazepam/alprazolam/flurazepam/lorazepam/medazepam/mexazolam/midazolam/temazepam compound and process patents from the 1960s–1990s.
• § 102 potential: None against any claim of the '414. They disclose the bare benzodiazepine APIs (e.g., diazepam itself) but none discloses the claimed closed carrier system (tocopherols 30–95% w/w + ethanol + benzyl alcohol 10–70% w/w + n-dodecyl β-D-maltoside). They are background citations for compound identity and manufacture.

F. Other face citations (nanoparticulate and mucosal-delivery published applications)

The uspto.report rendering shows the examiner also listed a long run of third-party published applications (mostly 2002–2007) directed to nanoparticulate drug formulations and mucosal/transmucosal delivery, including: 2002/0168402 and 2003/0031719 (Kipp et al.), 2003/0095928 (McGurk), 2003/0100755 (Sham), 2003/0118547 (Vandenberg), 2003/0118594 (Nag), 2003/0158206 (Billotte), 2003/0170206 (Rasmussen), 2003/0170752 (Andersen), 2003/0181411 (Bosch), 2004/0101482 (Sanders), 2004/0115135 (Quay), 2004/0126358 (Warne), 2004/0141923 (Dugger), 2004/0147473 (Warrell), 2004/0209814 (Nauck), 2004/0248846 and 2004/0258663 (Quay), 2005/0130260 (Linden), 2005/0153956 (Merkus), 2005/0215475 (Ong), 2005/0234101 (Stenkamp), 2006/0074025 (Quay), 2006/0106227 (Reddy), 2006/0178290 (Bara), 2006/0183674 (Brand), 2006/0198896 (Liversidge), 2007/0059254, and others continuing through the mid-2000s.

• Description/§ 102 potential: These are nanoparticulate-suspension and mucosal-permeation references that correspond to the suspension embodiments described (but no longer claimed) in the specification, and to the general Intravail enhancer literature. None individually anticipates claims 1–18, all of which are closed-form solution claims. At most they are cumulative § 103 background.

4. The one reference the pending IPR treats as the primary art (not a face citation I can fully verify)

11. Gwozdz, WO 2009/120933 A2 (also rendered in family databases as WO-2009121039-A2, published ~Sept. 30–Oct. 1, 2009)

• Description: PCT publication in the Hale Biopharma/Neurelis benzodiazepine-nasal-delivery family (Gwozdz is a named inventor of the '414). Per the prior litigation summary (IPR2025-00465, Padagis US LLC v. Neurelis Inc.), Padagis challenges claims 1–18 as obvious over this WO publication in view of Meezan (US 2006/0046962), and the PTAB has instituted trial.
• § 102 potential: Contested. Because this WO publication is in the same priority family (claiming the same March 28, 2008 provisional) and shares inventors with the '414, Neurelis has disputed its availability as prior art (motion to strike / discretionary-denial request; the Acting Director declined discretionary denial in a decision designated informative Jan. 9, 2026). Whether it can function as § 102 art turns on facts (e.g., whether the WO names the same inventive entity and whether it is truly "by others") that are not resolvable from the face record. Notably, the IPR itself frames the challenge under § 103 obviousness, not § 102 anticipation — an implicit concession that no single reference, including Gwozdz, discloses the full closed combination.

5. Bottom line on § 102 anticipation

• No reference cited on the face of the '414 patent individually anticipates any of claims 1–18. Claims 1 and 11 are closed "consisting of" nasal solutions requiring the specific combination of (i) diazepam, (ii) tocopherol(s)/tocotrienol(s) at 30–95% w/w (α-tocopherol only in claim 11), (iii) both ethanol and benzyl alcohol at a combined 10–70% w/w, and (iv) n-dodecyl β-D-maltoside. Dependent claims 2–10 and 12–18 merely narrow concentrations and amounts and inherit the same unmet combination.
• The closest references each supply only a subset: the Cartt '546/'865 family supplies the diazepam + tocopherol + alcohol/genus concept but not both alcohols + DDM in closed form (and is not § 102 art in any event); the Meezan/Maggio/Quay/Intravail line supplies only the alkyl-glycoside enhancer; the Wermeling line supplies only nasal benzodiazepine delivery; the Young/TPGS/nanoparticulate line supplies only tocopherol-excipient or suspension concepts; and the 1960s–90s synthesis patents supply only the bare benzodiazepine compounds.
• Accordingly, the realistic attack on the '414 claims is obviousness under pre-AIA § 103 over Gwozdz (WO 2009/120933) in view of Meezan (US 2006/0046962) — exactly the ground instituted in IPR2025-00465 — not anticipation under § 102.

6. Confidence and uncertainty notes

• High confidence: the identity of the patent; the closed scope of claims 1 and 11 (verified against DrugPatentWatch and the official PDF); the family relationship of 8,895,546 and US 2009/0258865; the face listing of 7,434,579, 8,895,546, 9,192,570, and the 2002–2007 published-application run; the § 102 analysis framework.
• Moderate confidence: exact titles and detailed disclosures of US 7,434,579, US 9,192,570, US 6,193,985, US 2006/0046962, and US 2006/0046969, which I could not individually verify from the available snippets; treat their descriptions above as context-based inferences.
• Not resolvable here: whether the complete front-page reference list contains additional references beyond those discussed (the official PDF shows more U.S. patents after 5,091,188 than could be extracted), and the precise publication number/title of the Gwozdz PCT (WO 2009/120933 vs. family-listed WO-2009121039-A2), which should be checked against the IPR petition exhibits and the official patent PDF if exact-string fidelity is required.

I'll research the prior art landscape for the '414 patent. The fetched patent text does not include the "References Cited" section from the Google Patents page, so I'll reconstruct it from searches. The key references already identified in this file's IPR analysis are Gwozdz (WO 2009/120933) and Meezan (US 2006/0046962) — I'll verify those and look for additional art.

The searches confirm the central IPR ground (Gwozdz + Meezan). Now I need the precise text of the '414 claims, the full Gwozdz reference (WO 2009/120933), and any additional art the PTAB or litigants have used (e.g., the Cartt reference from the parent-patent IPR, and other secondary references).

Note on sources and date: The fetched patent text contains no "References Cited / Prior Art" section (Google Patents page omitted it), so I reconstructed the operative prior art record from the PTAB/IPR filings and exhibit lists, which are the authoritative obviousness record for this patent. I also flag a date discrepancy: the task header states "Current Date: April 26, 2026," while the system prompt and earlier generated sections use 2026-09-09 (with the IPR2025-00465 Final Written Decision projected for ~2026-09-17). The obviousness analysis below is judged as of the claims' effective filing date (~2008–2009) and is unaffected by that discrepancy.

Obviousness Analysis — U.S. Patent 11,241,414 B2 (the "'414 patent")

1. The claims in issue

The '414 patent has 18 claims; claims 1 and 11 are the only independent claims, and both are closed "consisting of" composition claims (verified against DrugPatentWatch's reproduction of the issued claims):

Claim 1: "A pharmaceutical solution for nasal administration consisting of: diazepam or a pharmaceutically acceptable salt thereof; one or more natural or synthetic tocopherols or tocotrienols, or any combinations thereof, in an amount from 30% to 95% (w/w); ethanol and benzyl alcohol in a combined amount from 10% to 70% (w/w); and n-dodecyl beta-D-maltoside."

Claim 11: identical, except the tocopherol component is limited to "one or more natural or synthetic α-tocopherols."

Dependent claims 2–10 and 12–18 narrow: diazepam concentration (1–20% w/v; 10–250 mg/mL; 20–50 mg/mL); enumeration of tocopherol/tocotrienol species (claim 5); tocopherol amounts (45–85% w/w; 60–75% w/w); combined ethanol+benzyl alcohol amounts (15–55% w/w; 25–40% w/w); and claim 10, which collapses to "diazepam, vitamin E, ethanol, benzyl alcohol, and n-dodecyl beta-D-maltoside."

Source: https://www.drugpatentwatch.com/p/patent-claims/11241414; https://mtec-sc.org/patents/US-11241414-B2

The "consisting of" language means no sixth component is permitted — a drafting choice that materially helps an obviousness challenger here, because the claimed four-component list maps directly onto a known base formulation (Gwozdz) plus one known single-component additive (Meezan), with no need to account for (or exclude) any other excipients.

2. The controlling prior-art ground and its threshold viability

The single ground instituted in IPR2025-00465 (Padagis US LLC v. Neurelis, Inc.) — all claims 1–18 — is obviousness over:

• Gwozdz et al., WO 2009/120933 A2, "Pharmaceutical Solutions and Method for Solubilizing Therapeutic Agents," published October 1, 2009, PCT/US2009/038518 filed March 27, 2009, claiming priority to US 61/040,558 (filed March 28, 2008); applicant Particle Sciences, Inc.; inventors Garry Thomas Gwozdz, Andrew Loxley, Mark Mitchnick. (EP equivalent EP 2271214; US national-phase publication US 2011/0038899 A1.) Primary reference.
• Meezan et al., US 2006/0046962 A1, "Absorption Enhancers for Drug Administration," published March 2, 2006 (App. 11/127,786, filed May 11, 2005; assignee Aegis Therapeutics LLC). Secondary reference supplying the alkyl-glycoside limitation.

A threshold point about why Gwozdz is prior art at all (this is case-dispositive in the IPR and was the subject of the Director's referral and the failed Neurelis certificate-of-correction maneuver): The '414 family claims priority to the '558 provisional (2008-03-28), but the n-dodecyl beta-D-maltoside / alkyl-glycoside limitation first appears in the '439 application filed March 27, 2009 — not in the '558 provisional. The PTAB has found (institution decision in IPR2025-00465, and previously in IPR2019-00451 on the near-identical parent claims) that the '558 provisional lacks written-description support for that limitation. Because the '414 claims are therefore entitled to no earlier effective date than March 27, 2009, and Gwozdz (a "by another" application under pre-AIA § 102(e), with an effective US filing date of March 28, 2008 via its own priority claim) precedes that date, Gwozdz is § 102(e) prior art. Neurelis was held estopped from relitigating Gwozdz's priority-date entitlement after IPR2019-00451, and its later attempt to invoke the pre-AIA § 103(c) joint-research-agreement safe harbor (which would have removed Gwozdz from the ground) was rejected by the Board as untimely (~7-year delay) and prejudicial (Paper 36, 2026-02-06; rehearing denied, Paper 39, 2026-03-20). Gwozdz's availability is thus, on the current record, well-supported.

Sources: ai-lab.exparte.com IPR2025-00465 pages; PTACTS downloads (Petition exhibit list, Ex. 1009 description); search.vpb.lt EP 2271214 bibliographic record; prior generated sections of this file (PTAB challenges).

3. Graham factor 1 — scope and content of the prior art

3.1 Gwozdz (WO 2009/120933) — the complete base formulation

Gwozdz discloses a pharmaceutical solution of a therapeutic agent "dissolved in one or more natural or synthetic tocopherols or tocotrienols … and one or more alcohols or glycols," with methods of treatment, expressly including mucosal/nasal administration. Material disclosures, per the PTAB record and the published PCT text:

• Drug: "[E]xemplary hydrophobic or lipophilic therapeutic agents which can be solubilized … include, but are in no way limited to … benzodiazepines such as Diazepam…" (Gwozdz 8:6–18); also lists ibuprofen, griseofulvin, cyclosporin, paclitaxel.
• Tocopherols/tocotrienols: the "family of natural and synthetic compounds, also known by the generic names tocols or vitamin E," expressly including α-, β-, γ-, δ-tocopherols and tocotrienols and esters/analogs; "Alpha-tocopherol is the most abundant and active form"; "In one embodiment … the tocopherol(s) and/or tocotrienol(s) employed is alpha-tocopherol"; amounts "from about 30% to about 99% (w/w)."
• Alcohols/glycols: examples expressly include "ethanol," "benzyl alcohol," propyl/butyl/pentyl alcohols and the C2–C5 glycols; amounts "from about 1% to about 70% (w/w)"; dehydrated (USP) ethanol preferred.
• Nasal route: "[P]harmaceutical solutions of the instant invention are particularly useful in formulations to be administered to mucosal membranes, i.e., the nasal mucosa or lungs of a subject."
• Enhancers: Gwozdz states the solutions "can contain … penetration enhancers, humectants, suspending and/or viscosity modifying agents … to enhance delivery and absorption of the drug compound" (10:11–16) — an express pointer toward adding an absorption enhancer.
• Solution form: the solution "is not an emulsion or vesicle" — consistent with the claimed "solution."

The overlap with claims 1 and 11 is direct: Gwozdz's tocopherol range (30–99% w/w) overlaps the claimed 30–95% w/w entirely at its lower bound and substantially throughout; its alcohol range (1–70% w/w, with ethanol and benzyl alcohol both named) contains the claimed combined ethanol+benzyl alcohol range (10–70% w/w); diazepam is expressly named; and Gwozdz's "alpha-tocopherol" embodiment maps claim 11 verbatim.

Sources: PTACTS IPR2025-00465 institution decision excerpts; IPR2019-00451 FWD (bannerwitcoff.com PDF); Ex Parte AI-Lab case summaries.

3.2 Meezan (US 2006/0046962 A1) — the missing alkyl-glycoside limitation

Meezan is directed to alkyl-glycoside absorption-enhancer compositions for nasal and other mucosal delivery, and discloses:

• Alkyl glycosides generally: "octyl-, nonyl-, decyl-, undecyl-, dodecyl-, tridecyl-, tetradecyl- … α- or β-D-maltoside, -glucoside or -sucroside" (¶58); "dodecyl-β-D-maltoside" expressly listed (¶56); dodecyl maltoside (DDM) described as a specifically preferred alkyl glycoside (¶¶61, 94).
• Drugs: applicable to "small molecule organic drug molecules" and expressly to "anti-seizure agents (topiramate, zonisamide)" (¶¶4, 52) — a POSA would read these teachings as applicable to diazepam (MW ≈ 284.7 Da, a small molecule; a benzodiazepine anticonvulsant in the same drug class as topiramate/zonisamide's anticonvulsant indication).
• Concentrations: alkyl glycoside "about 0.01% to 20% by weight," preferred ~0.01–5%, ~0.01–2%, ~0.01–1%, "most preferably about 0.01–0.125%"; with 0.25% and 0.125–0.5% dodecyl maltoside exemplified (¶¶70, 149–151, 158; Table I).
• Carrier compatibility (critical for the non-aqueous Gwozdz combination): the therapeutic composition "can consist of a pharmaceutically acceptable carrier," defined as "an aqueous or non-aqueous agent, for example alcoholic or oleaginous, or a mixture thereof," expressly including "benzyl alcohol" among acceptable carrier substances (¶74). This is the disclosure that answers the only colorable mismatch between the references — Meezan's data are largely aqueous — and it was the basis on which the PTAB rejected Neurelis's "no motivation to combine" argument in IPR2019-00451.
• Results: intranasal bioavailability of a benchmark peptide raised from ~3% (no enhancer) to ~43% (0.125% TDM) and ~90% (0.25%), with variability cut to ±8% (¶¶150–151, Fig. 1) — a strong, quantitative reason to add an alkyl glycoside to an intranasal formulation and a concrete expectation of success.

Source: full text retrieved via Docket Alarm (Ex. 1011 in IPR2019-00451) and uspto.report; PTACTS petition excerpts.

3.3 Corroborating art (bolsters motivation; not strictly needed)

• Cartt '784 ("Nasal Administration of Benzodiazepines," Ex. 1015 in IPR2019-00451): discloses intranasal benzodiazepine dosing regimens (one nostril; both nostrils; first→second→first, optionally →second again), acknowledges the drug "may be fully soluble in the liquid," non-aqueous media, lists ethanol and benzyl alcohol as useful solvents, and discloses alkyl-glycoside absorption enhancers. In IPR2019-00451 the Board found Gwozdz + Meezan'962 + Cartt '784 rendered the method/dosing claims 17–23 of the parent '876 patent obvious. For the '414's composition claims, Cartt is not needed, but it corroborates that combining all four claimed components in an intranasal benzodiazepine context was conventional.
• Commercial diazepam formulations (PDR; Ex. 1017/1031 in the IPR record): Diastat® (diazepam rectal gel) and Valium® (diazepam injectable) both used ethanol and benzyl alcohol as co-solvents with diazepam — historic, commercial proof that the claimed alcohol pair was a routine, compatible solubilization choice for diazepam, independent of Gwozdz.
• Handbook of Pharmaceutical Excipients / USP monographs (Ex. 1016, 1038): standard reference data for ethanol, benzyl alcohol, α-tocopherol — relevant to the POSA's routine optimization of the three-solvent ratios.
• EPO counterpart proceeding (EP 2271214, filed against the Gwozdz family): the European examiner expressly found "no unexpected effect whatsoever has been demonstrated … for the selection of the claimed individual amounts of ethanol and benzyl alcohol," and that the POSA "would consider adjusting the amounts … by mere routine experimentation and, by doing so, would inevitably arrive at the claimed amounts" (EP FH, Ex. 1040 in the IPR record). While not U.S. law, this is persuasive evidence of non-criticality of the ranges.

4. Graham factor 2 — differences between the claims and the prior art

Element-by-element for claim 1 (claim 11 is identical except for the α-tocopherol restriction):

For claim 11, Gwozdz's statement that "alpha-tocopherol is the most abundant and active form" and its express embodiment employing alpha-tocopherol satisfies the species restriction directly.

The only true difference between the combined prior art and claim 1 is the selection of the specific alkyl glycoside, n-dodecyl β-D-maltoside, from Meezan's genus — and Meezan names dodecyl β-D-maltoside as a preferred species with exemplified concentrations. That is a textbook case of a disclosed preferred embodiment, not a novel selection.

Sources: claim text (DrugPatentWatch); Gwozdz text (PTACTS petition excerpts, Ex. 1009); Meezan text (¶¶56–61, 70, 149–151, Table I).

5. Graham factor 3 — level of ordinary skill

Consistent with the IPR record (Dr. Peppas, Dr. Donovan, Dr. Wermeling declarations), a POSA is a pharmaceutical formulation scientist with experience in transmucosal/intranasal drug delivery and solubilization of poorly water-soluble drugs, holding at least a graduate degree or equivalent industry experience, and familiar with FDA/ICH excipient and bioavailability practice. Nothing in the claims requires a specialist beyond that profile; the art at issue (solvent systems, absorption enhancers, intranasal dosing) is squarely within it.

6. Motivation to combine and reasonable expectation of success

6.1 Why a POSA would combine Gwozdz with Meezan

1. Gwozdz's own express invitation. Gwozdz lists "penetration enhancers" among the excipients its solutions "can contain … to enhance delivery and absorption of the drug compound" (10:11–16). A POSA seeking to improve Gwozdz's intranasal diazepam solution would look to the known art on intranasal penetration enhancers — and Meezan is the leading reference in that field.

2. A known, unsolved problem pointing to the enhancement strategy. Benzodiazepines such as diazepam have poor aqueous solubility, which limits the drug load deliverable in the small volumes (~25–200 μL) an intranasal spray can hold; Gwozdz solved solubility with the tocopherol/alcohol system but was directed to solubility, not mucosal permeation. Meezan supplied the complementary, recognized formulation strategy — alkyl glycosides — for increasing absorption and bioavailability of intranasally delivered drugs, expressly including small-molecule and anti-seizure drugs. Adding a permeation enhancer to a solubilized intranasal formulation to increase bioavailability of a rapid-onset seizure treatment is the paradigmatic "combination of familiar elements according to known methods [that] yields predictable results" (KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007)).

3. Meezan's teachings are commensurate with Gwozdz's non-aqueous system. Neurelis's principal objection — that Meezan's alkyl glycosides were only shown in aqueous formulations and would not function (or would precipitate diazepam) in a non-aqueous tocopherol/alcohol solution — was considered and rejected by the PTAB in IPR2019-00451 on the '876 parent (near-identical claims), affirmed by the Federal Circuit (Rule 36, Neurelis v. Aquestive, Appeal No. 2021-1038). The Board credited Dr. Wermeling that Meezan ¶74 expressly teaches carriers that are "aqueous or non-aqueous … for example alcoholic or oleaginous," naming benzyl alcohol as a carrier substance, and that a POSA would use a penetration enhancer to "adjust the rate and amount of drug absorbed purely intranasally" even where bioavailability is already decent. The institution decision in IPR2025-00465 applied the same reasoning to the '414's DDM-specific claim, noting Neurelis "already litigated and lost" the alkyl-glycoside motivation issue and would need to explain why picking Meezan's preferred alkyl glycoside (dodecyl maltoside) is a "materially distinct question of patentability." This is a strong, on-point motivation finding that a challenger can invoke.

4. The specific selection of n-dodecyl β-D-maltoside is a routine choice from an express list. Meezan names dodecyl β-D-maltoside as a species and DDM as preferred, with dose-response data and a preferred 0.25% level; the identity of the alkyl glycoside is not critical to the claimed function (no criticality or unexpected results shown in the '414 specification). Selecting a named preferred enhancer at a taught concentration is routine optimization, not invention.

5. Independent corroboration from commercial diazepam formulations. Diastat (rectal gel) and Valium (injection) had long combined diazepam with ethanol and benzyl alcohol, showing the three-drug/alcohol components were mutually compatible and that ethanol/benzyl alcohol were "readily miscible" — defeating any suggestion that the claimed solvent pair was unusual or that adding a further excipient would precipitate diazepam (the Board credited this testimony in IPR2019-00451).

6. Reasonable expectation of success. Gwozdz already demonstrated a stable, concentrated diazepam solution in tocopherol/ethanol/benzyl alcohol. Meezan demonstrated that adding 0.125–0.25% alkyl glycoside to an intranasal formulation raised bioavailability several-fold (3% → 43–90%) with reduced variability and no mucosal irritation. The combination is a simple admixture of a drug solution with a known, low-concentration, non-toxic, nonionic enhancer that Meezan states is compatible with alcoholic carriers. The Board in IPR2019-00451 found the same expectation-of-success showing sufficient, and Dr. Donovan's testimony in IPR2025-00465 reiterates it (the Board credited it at institution). Per the Board's institution decision, "Gwozdz demonstrated a stable and effective solvent system for diazepam, solving the core solubility problem" — the POSA would expect the enhancer to add permeation benefit without destroying solubility.

6.2 Obviousness of the specific ranges and species (dependent claims; prima facie case)

• Tocopherol 45–85% and 60–75% w/w (claims 6–7, 15–16); alcohols 15–55% and 25–40% w/w (claims 8–9, 17–18): These are narrower bands wholly inside Gwozdz's disclosed 30–99% (tocopherol) and 1–70% (alcohols) ranges. Under In re Peterson, 315 F.3d 1325 (Fed. Cir. 2003), selecting any value within a disclosed range is prima facie obvious. Nothing in the '414 specification demonstrates criticality at the claimed sub-ranges; the EPO examiner's finding of "no unexpected effect" for the ethanol/benzyl alcohol amounts is directly on point.
• Diazepam 1–20% w/v, 10–250 mg/mL, 20–50 mg/mL (claims 2–4, 12–14): Gwozdz's whole purpose is high drug loading in small volumes for mucosal delivery; the concentrations are routine solubility-driven optimization. Meezan's 0.25% enhancer level is likewise a taught preference.
• Claim 5 (species enumeration α-, β-, γ-, δ-tocopherols/tocotrienols, tocophersolan): every listed species appears in Gwozdz's vitamin-E family disclosure.
• Claim 10 ("diazepam, vitamin E, ethanol, benzyl alcohol, and n-dodecyl beta-D-maltoside"): this is literally the Gwozdz (diazepam + vitamin E + ethanol + benzyl alcohol) + Meezan (DDM) combination.

6.3 Secondary considerations

The IPR record (both IPR2019-00451 and the institution-stage papers in IPR2025-00465) found secondary considerations weak at best: no unexpected results, no long-felt unmet need shown to be solved by the specific DDM-containing non-aqueous solution (intranasal benzodiazepine delivery itself was an active field, with nasal midazolam/diazepam studies and the later commercial products Nayzilam and VALTOCO), and commercial success (VALTOCO) was not shown to be attributable to the claimed features rather than to regulatory exclusivity, device design, and commercialization. A challenger should expect the usual Neurelis rebuttal arguments — (i) the '558-provisional written-description/priority defense (largely foreclosed by the IPR2019-00451 collateral-estoppel finding and the failed JRA/certificate-of-correction maneuver), (ii) non-aqueous incompatibility of alkyl glycosides (rejected twice), and (iii) teaching away via the Handbook's note on nonionic surfactants inactivating ethanol/benzyl alcohol antimicrobial activity (rejected in IPR2019-00451 because the terminal formulation is aseptic and enhancer levels are minuscule).

7. Alternative and backup combinations

If, for any reason, the Gwozdz+Meezan ground falters (e.g., a FWD favorable to Neurelis, or a CAFC reversal on Gwozdz's priority date), the following fallback combinations from the same record are available to a challenger not estopped by § 315(e)(2):

1. Gwozdz + Meezan + Cartt '784 — adds the nasal dosing regimen art (single nostril, split dosing, timed re-dosing) and confirms alkyl-glycoside use in benzodiazepine nasal compositions. This combination already carried the method claims 17–23 of the parent '876 patent in IPR2019-00451; on the '414's composition claims it is cumulative but corroborative.
2. Gwozdz + Meezan + commercial diazepam labels (Diastat/Valium; PDR) — to independently establish that the ethanol+benzyl alcohol pair with diazepam was conventional and to rebut any "no motivation to include both alcohols" argument.
3. Gwozdz alone against claims that do not require the specific β-anomer or DDM (not applicable to claims 1–18 as issued, all of which require n-dodecyl beta-D-maltoside) — so Meezan (or an equivalent DDM-disclosing reference such as U.S. Pat. No. 5,661,130, incorporated into Meezan and cited throughout the '414 specification for the alkyl-glycoside enhancer class) is the necessary secondary reference for every claim.
4. KR 10-1517415 B1 (SK Biopharm, transnasal anticonvulsive compositions of poorly soluble anticonvulsants) and Loftsson/Gudmundsdottir cyclodextrin-benzodiazepine nasal work are less on-point (aqueous/cyclodextrin systems) and are unlikely to beat Gwozdz+Meezan; they are listed for completeness but are not the strongest art.

The dominant and by far best-supported ground remains Gwozdz (WO 2009/120933) in view of Meezan (US 2006/0046962) — the exact ground instituted on all 18 claims in IPR2025-00465, the exact ground on which the near-identical parent claims were held unpatentable in IPR2019-00451 (affirmed by the Federal Circuit), and a ground the Board has twice found satisfies motivation and reasonable-expectation-of-success despite Neurelis's priority-date, non-aqueous-compatibility, and teaching-away arguments.

8. Bottom line

Under 35 U.S.C. § 103, claims 1–18 of the '414 patent are very likely obvious over Gwozdz (WO 2009/120933) in view of Meezan (US 2006/0046962):

• Claim 1 reads onto Gwozdz's disclosed diazepam/vitamin-E(30–99%)/ethanol+benzyl-alcohol(1–70%) intranasal solution plus Meezan's expressly preferred n-dodecyl β-D-maltoside enhancer at taught concentrations; the overlapping ranges make the claimed amounts prima facie obvious absent any shown criticality.
• Claim 11 is even easier, because Gwozdz expressly prefers α-tocopherol.
• The dependent claims merely carve conventional sub-ranges out of the same disclosures.
• Motivation and reasonable expectation of success are strongly supported: Gwozdz itself points to penetration enhancers; Meezan teaches the enhancer class for intranasal small-molecule/antiseizure drugs, in carriers it expressly says may be non-aqueous/alcoholic; commercial diazepam-ethanol-benzyl alcohol products corroborate compatibility; and the PTAB has twice credited expert testimony reaching exactly this conclusion on materially identical claims.
• Secondary considerations are weak on the record, and Neurelis's principal procedural defenses (priority date, JRA safe harbor) have already been rejected or estopped.

The only scenario in which this conclusion would not hold is if the claims were ultimately accorded the 2008 provisional priority date (removing Gwozdz as § 102(e) art) — but that outcome is contrary to the Board's written-description findings in both IPR2019-00451 and the IPR2025-00465 institution decision, and the Final Written Decision due ~September 17, 2026 is expected to resolve the issue with strong odds favoring the challenger on the existing record. As of the operative date of this analysis, no FWD has issued and all 18 claims remain legally in force and untested by a final merits decision.

Key sources: DrugPatentWatch claims page (https://www.drugpatentwatch.com/p/patent-claims/11241414); Gwozdz WO 2009/120933 bibliographic record (search.vpb.lt; PTACTS petition exhibits); Meezan US 2006/0046962 full text (Docket Alarm/PTACTS); IPR2025-00465 institution decision and papers (PTACTS); IPR2019-00451 Final Written Decision (bannerwitcoff.com PDF); Ex Parte AI-Lab case summaries for IPR2025-00465.