US 12324852

I'll verify the patent's current status via search, then compile the summary from the authoritative text provided.

Let me pull the full claim set to accurately characterize each independent claim.

US Patent 12,324,852 — Analyst Summary

Verification note up front: I retrieved this patent by its exact number, 12,324,852 (no auto-correction applied). Everything below is either taken from the authoritative full text supplied to me or from search results, which are cited. Where the two conflict, I flag it rather than reconcile it silently.

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1. Bibliographic Data

Prosecution/assignment history appearing in the record: security interest to Orbimed Royalty & Credit Opportunities III, LP (2021-08-06); assignment from Hale Biopharma Ventures, LLC to Neurelis (2021-12-13); release by secured party (2024-11-14). The application is a continuation in a chain that also yielded US 12,337,061 B2 (issued 2025-06-24) and US 12,521,400 B2 (issued 2026-01-13).

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2. Abstract

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

(Abstract as recorded on Google Patents and confirmed identically on DrugPatentWatch.)

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3. Plain-Language Overview of the Independent Claims

Important caveat on sourcing. The authoritative patent text I was provided is truncated — it ends partway through the specification and does not include the claims section. The claim characterizations below come from third-party databases that render the granted claims; those renderings are themselves visibly truncated with ellipses in several places (notably claims 6 and 10, where the excipient quantities are elided). I therefore describe claim scope in substance, and quote only the portions I can see verbatim. Treat the numbers as reliable but not as a substitute for the face of the patent.

General character of the claims: Every independent claim is a method-of-use (method of treating) claim, not a composition claim. The claim family is narrow and product-specific: it is tied to the Valtoco formulation (vitamin E USP / diazepam / dodecyl maltoside / benzyl alcohol / ethanol), to a 100 µL single metered nasal spray, and to a quantified intravenous-equivalence bioavailability with a clinical outcome. This is materially narrower than the broad "30%–95% tocopherol, 10%–70% alcohol" genus described in the specification.

Claim 1 (single 10 mg spray, one nostril). A method of treating "bouts of intermittent and stereotypic episodes of increased seizure activity" (i.e., seizure clusters) in an epilepsy patient, the bouts being distinguishable from the patient's other seizures. Steps: administer a single 100 µL spray to one nasal mucosal membrane of a solution consisting of 56.47 mg vitamin E USP ±5%; 10 mg diazepam; 0.25 mg dodecyl maltoside; 10.50 mg benzyl alcohol ±5%; and q.s. ethanol. Two further limitations: (a) administration achieves 92.5%–107.5% of the bioavailability of an equivalent IV diazepam dose and is safe and effective for those bouts; and (b) administration results in a treatment selected from reduction in seizure severity, reduction in probability of a repeat seizure, increase in the interval to the next seizure, reduction in seizure frequency, and combinations thereof.

Claim 6 (two 7.5 mg sprays, both nostrils). Same patient population, but the step is a single 100 µL spray to one nasal mucosal membrane plus a second single 100 µL spray to the other. The solution is a "stable pharmaceutical solution" and the diazepam content is 7.5 mg; the same 92.5%–107.5% IV-bioavailability and safety/effectiveness limitations apply. (The other excipient amounts are elided in the database rendering, but the two-spray/7.5 mg structure is clear.)

Claim 10 (single 5 mg spray, one nostril). Same as claim 1 but the solution contains 5 mg diazepam, with the same 92.5%–107.5% IV-bioavailability limitation and the same open-ended list of treatment outcomes.

Claim 14. A further independent method claim in the same family; the rendering is truncated before the limitations, so I cannot state its precise scope with confidence. Given the pattern, it most likely recites another single-spray or two-spray variant with different quantitative bioavailability wording (compare the sibling '061 patent, whose independent claims recite "96%–97%" bioavailability rather than "92.5%–107.5%").

Dependent claims (2–5, 7–9, 11–13, 15): narrow the above to (i) 96% IV bioavailability; (ii) Tmax of about 1.5 hours; (iii) a solution substantially free of water; and (iv) the 100 µL dose given as a single metered spray.

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4. Litigation and Docket Status (as of searches run 2026-09-10 date context)

District court — all in D. Delaware, Judge Maryellen Noreika, 35 U.S.C. § 271(e)(2)/§ 271 patent infringement over generic Valtoco ANDAs:

• Neurelis, Inc. v. Padagis LLC, No. 1:24-cv-00562 (filed 2024-05-08) — this is the first case that put the '852 patent in suit, alongside U.S. 8,895,546; 11,241,414; 11,793,786; 12,268,664; 12,337,061.
• No. 1:25-cv-01228 (filed 2025-10-03) and No. 1:25-cv-01443 (filed 2025-11-26) — consolidated actions adding the '852 and '061 patents.
• Neurelis, Inc. v. Padagis LLC, No. 1:26-cv-00401 (filed 2026-04-08) — adds U.S. 12,521,400.
• Neurelis, Inc. v. Strides Pharma Global PTE Ltd., No. 1:26-cv-00947 (filed 2026-07-31) — asserts 11,241,414; 11,793,786; 12,268,664; 12,324,852; 12,337,061; 12,521,400; 12,599,611.
• Amneal action (No. 1:26-cv-00258, filed 2026-03-11).

In the '852-specific pleadings, Neurelis pleads that the '852 patent issued June 10, 2025, that it is listed in the Orange Book with an expiration of October 16, 2032, and that Padagis's and Strides' Paragraph IV certifications allege invalidity, unenforceability and/or non-infringement. Padagis is alleged to meet at least each limitation exemplified in claim 1.

PTAB: Three instituted IPRs — IPR2025-00464, -00465 and -00466 — directed to the '546, '414 and '786 patents (trial date scheduled 2026-06-16). None of these challenges the '852 patent, so as of this search there is no PTAB validity proceeding against the '852 claims.

CAFC (2026): I found no Federal Circuit appeal involving U.S. 12,324,852 in the 2026 dockets searched. That is a negative finding from public docket aggregators, not a certificate that none exists. Because the PTAB trials on sibling patents were still pending in mid-2026 and the district court bench trial is scheduled for 2027-03-01, any appeal of a decision on the '852 patent would necessarily postdate this search.

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5. Points of Uncertainty — Explicitly Flagged

1. Claims text is second-hand. The authoritative full text I was given omits the claims. My claim summary relies on DrugPatentWatch and on a district-court complaint quoting claim 1. Two of the independent claims (6 and 10) are truncated in that source, so the full excipient quantities for the 7.5 mg and 5 mg embodiments are not established here. Confirm against the printed patent or Patent Center before relying on it.
2. Priority date conflict. Google Patents lists the priority date as 2011-06-14, while TheraRadar attributes family 47357711 to a 2008-03-28 priority (nominal global expiry 2028-03-28, with U.S. PTA pushing the Orange Book date to 2032). Both cannot be the whole story; the '852 patent is a continuation in a long chain, and different databases anchor the "family" differently. Do not treat either date as conclusively established from these sources.
3. Claim count. I can confirm independent claims 1, 6, 10 and 14 and dependents through at least claim 15, but I cannot confirm the total claim count of the '852 patent from the material available. A sibling patent in the same family ('061) is reported as having six independent claims; I have not assumed the same for '852.
4. Assignee status. Google Patents notes the assignee listing is not a legal conclusion; the Orbimed security interest and its later release complicate a clean chain-of-title statement. Current assignee is reported as Neurelis, Inc.
5. Expiration date is an adjusted/estimated figure. 2032-10-16 reflects PTA as reported; it is not a legal determination and would change if any claim is held invalid or if terminal disclaimer/PTA recalculation occurs.

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One-line bottom line

US 12,324,852 is a Neurelis, Inc. method-of-use patent, issuing 2025-06-10 from application 17/336,389 filed 2021-06-02, whose independent claims narrowly cover intranasal treatment of epilepsy seizure clusters by administering a 100 µL spray of the specific Valtoco solution (vitamin E USP, diazepam at 10/7.5/5 mg, dodecyl maltoside, benzyl alcohol, ethanol) to one or both nostrils, tied to a 92.5%–107.5% intravenous-equivalence bioavailability and defined clinical outcomes — and it is currently asserted against generic ANDA filers in several D. Delaware actions, with no PTAB or Federal Circuit proceeding against it found.

I'll search for litigation involving this specific patent number.

Let me dig deeper into specific cases and PTAB proceedings.

Let me check the PTAB and any appellate activity specific to this patent.

Litigation involving U.S. Patent No. 12,324,852

Patent identified literally as: US 12,324,852 B2 — "Administration of Benzodiazepine Compositions"; application US 17/336,389; filed 2021‑06‑02; granted 2025‑06‑10; priority date 2011‑06‑14; current assignee Neurelis Inc.; adjusted expiration 2032‑10‑16. It is Orange‑Book‑listed against Neurelis's VALTOCO® (diazepam nasal spray), NDA No. N211635.

Yes — litigation is known, and it is extensive. All of it is Hatch‑Waxman ANDA litigation filed by Neurelis in the U.S. District Court for the District of Delaware (all before Judge Maryellen Noreika). The '852 patent is a comparatively young patent (granted June 2025) and was added to the Valtoco litigation campaign in late 2025/2026.

District court cases asserting (or listing) the '852 patent

Note on case numbers: Neurelis, Inc. v. Lupin Inc. et al., 1:26‑cv‑00258‑MN (filed Mar. 11, 2026), asserts only U.S. 12,521,400 according to the docket's Patent/Trademark report, so the '852 patent does not appear to be asserted in that particular complaint.

PTAB (post‑grant) proceedings

• The three Padagis IPRs I located — IPR2025‑00464, IPR2025‑00465, IPR2025‑00466 (filed Jan. 17, 2025, all instituted for trial) — challenge U.S. 8,895,546, 11,241,414 and 11,793,786 respectively. None of them is directed to 12,324,852. IPR2025‑00464 has a projected final written decision due Sept. 17, 2026.
• I found no IPR, PGR, or other PTAB proceeding specifically challenging U.S. 12,324,852. I cannot rule out a recently filed petition that is not yet indexed, but nothing in the sources reviewed names the '852 patent as a challenged patent.

Appellate (CAFC)

• No Federal Circuit appeal involving 12,324,852 was found. That is expected given the cases are still in district court. A CAFC appeal would only arise from a final judgment or from the instituted IPRs (which concern other patents).

Outcome / current status summary

• No case involving the '852 patent has reached final judgment. All identified matters are pending.
• Cases are being centrally managed: Delaware's Second Consolidation Order and Modified Case Scheduling Order (Apr. 23, 2026) consolidated the Valtoco ANDA actions under lead case 1:24‑cv‑00562‑MN, with a bench trial anticipated for the week of Jan. 10, 2028 (per the court's oral order of Mar. 25, 2026). Fact discovery, expert reports, and Markman briefing are running through 2026 (Markman hearing set for 8/19/2026 in the consolidated schedule).
• Related reported activity: Neurelis publicly stated that the '852 and '061 patents extend Valtoco protection through October 2032.
• The Google Patents "family has litigation" flag for this patent links exactly four Delaware district‑court matters — 1:26‑cv‑00261, 1:25‑cv‑01443, 1:25‑cv‑01228, and 1:24‑cv‑00562 — consistent with the table above.

Important caveats

1. Date discrepancy: You stated today is April 26, 2026, but several sources I retrieved carry update stamps and filing entries dated July–August 2026 (e.g., the Strides complaint filed 2026‑07‑31, a DrugPatentWatch page "Last Updated: August 3, 2026," and a PTAB docket entry dated 4/13/2026). I report those dates as they appear in the sources rather than adjusting them; you may want to confirm the current date and the very latest docket entries directly on PACER.
2. Some dockets (e.g., 1:26‑cv‑00401) were only partially visible in the sources retrieved; the specific patents listed and status should be verified on PACER/CourtListener.
3. The '852 patent is a method‑of‑use patent (claims recite administering a 100 µL single spray of a defined diazepam/vitamin E/dodecyl maltoside/benzyl alcohol/ethanol solution achieving 92.5–107.5% IV bioequivalence). It is one of several Neurelis patents asserted against multiple ANDA filers, which is why it appears in so many parallel Delaware cases.

Primary sources consulted: U.S. District Court (D. Del.) dockets and filings via CourtListener, PacerMonitor, Justia Dockets, Docket Alarm; DrugPatentWatch patent‑12,324,852 litigation page; ParagraphFour Valtoco case tracking; Robbins Kaplan Hatch‑Waxman "New ANDA Cases" bulletins (Q4 2025); Google Patents US12324852B2 litigation links; PTAB dockets (IPR2025‑00464/465/466).

I'll start by checking the structured record against live sources, since the ODP block says no AIA trials are indexed.

Key signal: the Padagis IPRs I found target the '546, '414, and '786 patents — not the '852 patent. Let me verify whether anything was filed against the '852 patent itself.

No IPR against the '852 patent has surfaced yet. Let me check the later-filed IPRs and whether the Padagis trials have reached final written decision (trial date reportedly 2026-06-16, now past).

Proceedings overview

Total AIA trial proceedings on US 12,324,852: 0. No IPR, PGR, or CBM has ever been filed against this patent; there is accordingly nothing in any status category — no active trial, no claims invalidated, no claims sustained, no settlement, no institution denial. The bottom line for a defendant is the inverse of a hardened patent: the '852 patent is forensically untested at the Board. Nobody has ever run a Gwozdz-based obviousness case against these claims, so there is no adverse FWD to cite and no IPR estoppel to hide behind — but there is also no PTAB precedent that the claims are good, and the Office's own prior rulings on this family (see IPR2019-00451, below) are, if anything, unhelpful to the patent owner.

I want to be explicit about a trap: a routine search for "Neurelis PTAB" returns three live Padagis IPRs (IPR2025-00464/465/466) and one decided Aquestive IPR (IPR2019-00451). None of them is a proceeding on US 12,324,852. They target sibling patents in the same family. If a demand letter or a litigation hold memo conflates them, that's an error you should correct before you build a defense on it.

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IPR2019-00451 — Aquestive Therapeutics, Inc. v. Neurelis, Inc. ⚠️ NOT a proceeding on US 12,324,852

Included because it is the single most consequential Board ruling touching this patent family, and the reason the family exists in its current form.

• Type: Inter Partes Review
• Patent challenged: US 9,763,876 (the '876 patent) — an ancestor in the same family, not the '852 patent
• Filed: 2019-01-29
• Status: Terminated — all claims held unpatentable; affirmed on appeal
• Judge panel: Not confirmed from the sources I could retrieve; I did not verify the APJ roster and won't guess it
• Petition grounds: § 103 obviousness, all 36 claims of the '876 patent. Counsel for petitioner Hoffmann & Baron, with experts Dr. Nicholas A. Peppas and Dr. Daniel P. Wermeling
• Final Written Decision: 2020-08-06 — the Board found all 36 claims unpatentable as obvious. As a predicate, the Board determined the challenged claims were not entitled to the priority date of provisional application 61/040,558 ("the '558 provisional"), which put Gwozdz into play as prior art
• Settlement / termination: None — decided on the merits
• Appeal: Appeal to the Federal Circuit by Neurelis. Docket No. 2021-1038 appears in the record as the appeal proceeding. The Federal Circuit affirmed the Board's unpatentability decision
• Defensive value: The '876 patent was the original Orange Book patent for VALTOCO, and it is dead. More importantly, the priority-date holding in this FWD is the doctrinal engine behind every subsequent challenge to this family — it is why the examiner's later contrary priority findings were treated as "material error."

Source: https://hbiplaw.com/library-posts/announcements/hoffmann-baron-on-behalf-of-aquestive-inc-successfully-invalidates-all-claims-of-orange-book-patent-for-valtoco-nasal-spray-in-aquestive-therapeutics-inc-v-neurelis-inc/

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IPR2025-00464 — Padagis US LLC v. Neurelis, Inc. ⚠️ NOT a proceeding on US 12,324,852

• Type: Inter Partes Review
• Patent challenged: US 8,895,546 (the '546 patent)
• Status: Active — instituted, trial stage. Projected FWD due date 2026-09-17 per the Acting Director's decision
• Institution decision: Initially the subject of a Director-level referral. Acting Director Coke Morgan Stewart declined discretionary denial and referred the petitions to the Board on 2025-07-16 (Paper 12), finding that the patent owner had shown no basis for denial. The Board then instituted
• Petition grounds: § 103 — claims obvious over Gwozdz (WO 2009/120933) in view of Meezan (US 2006/0046962). Petitioner also pressed collateral estoppel from IPR2019-00451 on priority date, Gwozdz's availability as art, and the Gwozdz + Meezan combination
• Notable event: Patent owner filed a statutory disclaimer on 2026-01-02 (Ex. 2075) on the '546 patent, and moved (unsuccessfully) for leave to seek a certificate of correction to add Joint Research Agreement disclosure. The Board denied rehearing on 2026-03-20
• Appeal: None yet — FWD not issued
• Defensive value: Opposing counsel in this family now has a fully briefed, judicially tested Gwozdz + Meezan obviousness record. That work product is portable to a '852 challenge.

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IPR2025-00465 — Padagis US LLC v. Neurelis, Inc. ⚠️ NOT a proceeding on US 12,324,852

• Type: Inter Partes Review
• Patent challenged: US 11,241,414 (the '414 patent)
• Status: Active — instituted, trial stage. Projected FWD due 2026-09-17
• Petition grounds: § 103 — Ground 1: claims 1–18 obvious over Gwozdz in view of Meezan. Petitioner's mapping: Gwozdz discloses the nasal diazepam solution with tocopherol at 30–99% (w/w) and ethanol + benzyl alcohol at 1–70% (w/w); Meezan supplies the alkyl glycoside (n-dodecyl beta-D-maltoside) as an intranasal absorption enhancer. Motivation: Gwozdz itself points to penetration enhancers; expectation of success from Meezan's compatibility with alcohol-based solvent systems
• Key issue: Priority. Petitioner argued the '414 patent is not entitled to the 2008-03-28 '558 provisional, so Gwozdz qualifies as art. Claim construction of "vitamin E" per the patent's express definition at col. 30, ll. 7–10
• Institution decision: Same Director-level referral and informative decision as IPR2025-00464. On referral, the Board "determined that the allegedly narrowed claims of the '414 and '786 patents did not find adequate written description support in the relevant priority applications or avoid Gwozdz as prior art." The Board instituted — meaning the priority defense that carried the day at the preliminary-response stage for the '546 patent failed for the '414 and '786 patents
• Petition practice note: Patent Owner moved to strike portions of Petitioner's reply, alleging word-limit violations and new theories/evidence. For my own part I note that the Board's claim-construction position on the '414 claims was adverse — good news for future challengers
• Defensive value: A petitioner has already been through institution on a materially identical formulation claim. The template is established; the marginal cost of extending it to the '852 claims is low.

Source: https://ai-lab.exparte.com/case/ptab/IPR2025-00465/doc/1026

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IPR2025-00466 — Padagis US LLC v. Neurelis, Inc. ⚠️ NOT a proceeding on US 12,324,852

• Type: Inter Partes Review
• Patent challenged: US 11,793,786 (the '786 patent)
• Status: Active — instituted, trial stage. Projected FWD due 2026-09-17
• Petition grounds: § 103 over Gwozdz in view of Meezan (parallel to -00465)
• Institution decision: Instituted — again, the Board rejected the claim that the narrowed '786 claims are supported by the priority applications or avoid Gwozdz
• Defensive value: Same as -00465. The '786 patent carries the same March 2029 Orange Book expiration as the '546 and '414 patents, so cancellation here would open the earliest generic entry date in the portfolio.

Authority for all three Padagis proceedings: Acting Director's decision declining discretionary denial and referring the petitions, 2025-07-16 (Paper 12), later designated informative by Director John Squires on 2026-01-09. See https://www.ptablitigationblog.com/informative-no-discretionary-denial-where-prior-ipr-suggests-material-error-by-office/ and the underlying paper at https://ptacts.uspto.gov/ptacts/public-informations/petitions/[1557270](/patent/1557270)/download-documents?artifactId=VoUlwZvj3EnKLPNr-_aKg51QijJtQzA96sxNFDyin9rO0JVAa4TR3gk

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Strategic summary

Claim status on US 12,324,852: entirely UNTESTED. No claim — independent or dependent — has been canceled, narrowed, or confirmed by the Board. The patent issued 2025-06-10 and has an adjusted expiration of 2032-10-16, giving it roughly six years of life. Compare that to the family history: the '876 patent's claims were all canceled via IPR2019-00451, and the '546, '414 and '786 claims are currently under instituted review. The '852 patent is the newest addition to the Orange Book listing and, so far, the only one nobody has attacked at the PTAB.

Estoppel landscape — this is where a defendant has room. Section 315(e)(2) estoppel is patent-specific: it bars a petitioner from raising, in a later civil action, grounds it raised or reasonably could have raised "with respect to that patent." Padagis's IPRs are directed to the '546, '414 and '786 patents. No estoppel from those proceedings attaches to the '852 patent. Practically, that cuts both ways:

• Available to you: the full Gwozdz + Meezan obviousness theory, and any other art, against the '852 claims. You are not boxed out of any ground.
• Available to the patent owner: Neurelis is not bound by any adverse claim construction on the '852 claims either. Any Phillips construction the district court or Board adopted for "consisting of," "vitamin E," or the bioavailability limitations in the sibling patents is informative but not binding.

A structural point worth developing early. The '852 patent claims priority to provisionals filed 2011-06-14 and 2011-12-13 — not to the 2008-03-28 '558 provisional that drove IPR2019-00451 and the Padagis priority disputes. Gwozdz (WO 2009/120933) published 2009-10-01, more than one year before the '852 priority date. On its face that makes Gwozdz available as prior art against the '852 claims regardless of how the priority fight resolves — which removes the single most powerful defense Neurelis deployed at the '546 preliminary-response stage. I flag this as my own analysis of the dates, not a finding I have verified in a Board decision on the '852 claims; confirm the priority chain and the applicable § 102 subsection against the '852 file history and intervening continuations before relying on it.

Pattern signals. (1) Padagis is a serial, repeat petitioner in this family — three petitions so far, all instituted, none against the '852 patent yet. (2) Neurelis litigates aggressively and in waves: it has filed successive Delaware ANDA suits as each new continuation issued (1:24-cv-00562; 1:25-cv-00821; 1:25-cv-01228 adding the '852 and '061 patents; 1:25-cv-01443 adding the '852 patent for Lupin; 1:26-cv-00401; 1:26-cv-00947 against Strides). Adding the '852 patent to an existing case is a deliberate life-cycle-management move to push exclusivity past the 2029 cluster. (3) No defensive aggregator appears in the chain. I found no Unified Patents, RPX, or other aggregator filing against this family; the challengers are competing ANDA filers with their own commercial motive. (4) On the patent-owner side, Neurelis has shown it will fight institution hard (discretionary-denial requests, motions to strike, certificate-of-correction maneuvers) — expect the same if you file.

One timing observation, since it is the most actionable thing in this memo. Under § 315(b), a petition is time-barred if filed more than one year after service of a complaint alleging infringement of the patent. The '852 patent has been asserted in complaints filed 2025-10-03 (D. Del. 1:25-cv-01228, Padagis), 2025-11-26 (1:25-cv-01443, Lupin), and 2026-07-31 (1:26-cv-00947, Strides). If those are the operative service dates, the corresponding § 315(b) windows close on or about 2026-10-03, 2026-11-26, and 2027-07-31 respectively. Do not calendar those without pulling the actual summons/service records — I am computing from filing dates and the bar runs from service, not filing.

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Recommended next steps

1. Correct the record internally first. If anyone on your team has represented that "the '852 patent was invalidated in IPR2025-00465" or "the '852 patent survived IPR," that is wrong on both counts. The correct statement is: no AIA trial has ever been instituted on US 12,324,852. This is consistent with the USPTO ODP structured record, which shows no AIA proceedings, and with the Google Patents record at https://patents.google.com/patent/US12324852/en, which lists litigation but no PTAB matters.

2. Treat the '852 patent as a live, unsullied threat — not a paper tiger. A defendant facing an assertion should not assume the family's IPR history weakens the '852 claims. The '414 and '786 patents beat back the priority challenge at the preliminary-response stage and still got instituted; the '852 patent has a later priority date (2011), which, if anything, makes prior art easier to establish, not harder.

3. Pull the three Padagis institution decisions and both FWDs the moment they issue. IPR2025-00464/465/466 are at the trial stage with a projected FWD due 2026-09-17 — one week after today's date. I could not confirm from available sources whether those FWDs have issued yet. Verify at USPTO PTAB E2E. If any of the '546, '414, or '786 claims are canceled, that is directly probative of how the Board reads the Gwozdz + Meezan combination, and it materially strengthens a parallel '852 petition.

4. Check whether the Board's priority holding travels. The Padagis institution decisions turned partly on the Board's rejection of the patent owner's priority claim for the '414 and '786 claims. Obtain the full institution decisions and the 2026-03-20 rehearing denial (IPR2025-00464, Paper 39) and analyze whether the same reasoning reaches the '852 claims' 2011 priority chain. Note that the '852 patent's different priority date means the reasoning may not transfer cleanly — analyze rather than assume.

5. Chart the § 315(b) clock today. Given the wave of Delaware complaints asserting the '852 patent, at least one petitioner's one-year window is likely closing in October 2026. If you are evaluating an IPR, determine your own service date and work backward 12 months. Do not rely on the dates I derived from filing records.

6. Watch the '061 and '664 patents too. US 12,337,061 (issued 2025-06-24, expires 2032-06-13) and US 12,268,664 (issued 2025-04-08) are also asserted and also un-challenged at the PTAB. The '664 patent's certificate of correction, obtained 2026-02-10 to invoke the 35 U.S.C. § 103(c)(2) Joint Research Agreement safe harbor, shows the patent owner is actively repairing validity defects exposed by the IPR2019-00451 estoppel narrative. That is a signal worth tracking for all three late-issuing continuations.

Summary judgment on the record: the absence of PTAB activity on US 12,324,852 is not a sign of weakness in the patent — it is a sign that the patent is new and has only recently entered the assertion campaign. That absence is itself the key strategic fact: nobody has tested these claims, so nobody knows how they hold up, and no estoppel constrains anyone.

I'll reconstruct the assignment record for US 12324852. Let me pull the primary sources.

Ownership Reconstruction — US 12,324,852 B2

Patent: Administration of Benzodiazepine Compositions · App. 17/336,389, filed 2021‑06‑02 · Issued 2025‑06‑10 · Priority date listed by Google Patents as 2011‑06‑14 · Adjusted expiry 2032‑10‑16 · Assignee of record: Neurelis, Inc. (San Diego, CA)

Sourcing caveat up front: USPTO Assignment Center (assignmentcenter.uspto.gov / assignment.uspto.gov) is a JavaScript application whose record detail pages are not exposed to search indexing, and I was unable to complete a direct reel/frame pull within this session. Everything below is grounded in (a) the Google Patents legal‑events record for this patent and (b) PTAB/docket documents that quote the underlying assignment records. I have not fabricated any reel/frame numbers. The only reel/frame that appears anywhere in the retrieved record is Reel 048271, Frame 0304, cited by Neurelis itself in its IPR2019‑00449 and IPR2019‑00451 mandatory notices as the recordation by which Neurelis owns the family's U.S. 9,763,876 — a sibling, not US 12,324,852. Treat all '852-specific reel/frames as unverified here.

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Inventors

Named on the face of US 12,324,852 (same seven‑person group as the sibling members of this family, e.g. US 11,241,414 and US 12,268,664):

Unusual patterns. None of the "inventor flight before a fire‑sale" pattern. What is unusual is the timing of perfection: all seven inventors' assignments to Hale BioPharma Ventures, LLC were recorded on a single day, 2021‑12‑13 — roughly ten and a half years after the 2011 priority date and about six months after this application was filed. The very same day, Hale BioPharma conveyed to Neurelis. That is a diligence‑driven chain‑of‑title cleanup across the whole family, not a distress sale: inventories sold off in fire‑sales do not usually get their inventor‑to‑entity links perfected on the way out the door, and Neurelis was simultaneously closing a royalty financing. I have no evidence of any inventor departing the original assignee within 12 months of filing, and I will not infer one.

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Original assignee

Hale BioPharma Ventures, LLC originated the family (applicant on WO 2012/174158; assignee of US 9,763,876), with Neurelis, Inc. as the front‑page assignee/applicant on the issued '852 and the recorded owner today.

• Business: Neurelis was founded in 2007 to develop, license and commercialize CNS drug candidates (D. Del. complaint, ¶23, filed in the Padagis/Lupin actions). It is not a licensing shell.
• Product embodying the claims: Yes, and it is unambiguous. Neurelis holds NDA No. N211635 for VALTOCO® (diazepam nasal spray), 5 / 7.5 / 10 mg per 0.1 mL, indicated for short‑term treatment of seizure clusters. The '852 is Orange Book‑listed against VALTOCO with a 2032‑10‑16 expiry.
• Current status: Operating, revenue‑generating, FDA‑approved product, active litigant. No bankruptcy, no dissolution, no acquisition of Neurelis itself in the record.

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Assignment timeline

Four post‑issuance/pre‑issuance events are recorded against this patent's record in the Google Patents legal‑events feed. The source does not expose reel/frame for any of the four, and I could not verify them at Assignment Center in this session — flagged as such below.

• 2021‑08‑06 (recorded) — Reel/frame not exposed in retrieved source

  • Conveyance: Security Interest (secured‑party grant)
  • Assignor / grantors: AEGIS THERAPEUTICS, LLC and NEURELIS, INC.
  • Assignee / secured party: ORBIMED ROYALTY & CREDIT OPPORTUNITIES III, LP
  • Correspondent: not determinable from the retrieved record — do not assume.
  • Context: Securitization — a royalty/revenue‑interest financing layered over the VALTOC patent estate, granted by both Neurelis and Aegis (the Intravail® alkyl‑glycoside licensor), consistent with a collateral pool covering both the drug and the enhancer technology.

• 2021‑12‑13 (recorded) — Reel/frame not exposed in retrieved source

  • Conveyance: Assignment of Assignors' Interest
  • Assignors: LOXLEY, ANDREW; MEDEIROS, DAVID; GWOZDZ, GARRY THOMAS; MITCHNICK, MARK; MAGGIO, EDWARD T.; HALE, DAVID; CARTT, STEVE (all seven inventors)
  • Assignee: HALE BIOPHARMA VENTURES, LLC
  • Correspondent: not determinable from the retrieved record.
  • Context: Chain‑of‑title perfection — inventor‑to‑entity nunc pro tunc cleanup, filed the same day as the entity transfer. No correspondent recurrence can be asserted here.

• 2021‑12‑13 (recorded) — Reel/frame not exposed in retrieved source

  • Conveyance: Assignment of Assignors' Interest
  • Assignor: HALE BIOPHARMA VENTURES, LLC
  • Assignee: NEURELIS, INC.
  • Correspondent: not determinable from the retrieved record. (For context, the prosecution firm of record on the sibling US 11,241,414 is Troutman Pepper Hamilton Sanders LLP; prosecution counsel and assignment correspondent are different roles and I have no evidence this firm filed the recordings.)
  • Context: Internal group reorganization — the originator incubator conveying the estate to the operating drug company ahead of/alongside the Orbimed royalty financing. Same‑day stacking with the inventor assignments indicates a coordinated diligence closing.

• 2024‑11‑14 (recorded) — Reel/frame not exposed in retrieved source

  • Conveyance: Release by Secured Party
  • Assignor / releasing party: ORBIMED ROYALTY & CREDIT OPPORTUNITIES III, LP
  • Assignees / released parties: AEGIS THERAPEUTICS, LLC and NEURELIS, INC.
  • Correspondent: not determinable from the retrieved record.
  • Context: Securitization unwind — the 2021 security interest was terminated, i.e. the Orbimed facility was repaid/refinanced or the collateral released. Neurelis remains owner.
  • Corroborating family evidence: Neurelis's own IPR2019‑00449/‑00451 mandatory notices identify Reel 048271, Frame 0304 as the recordation of its ownership of the family's US 9,763,876 — the same Hale BioPharma → Neurelis conveyance pattern reflected here.

Not a recorded assignment, but part of the ownership picture: the later continuations claim priority to this estate — US 17/721,595 (→ US 12,337,061, 2022‑04‑15) and US 19/219,706 (→ US 2025/0281394, 2025‑05‑27). All sibling grants (US 11,241,414; 11,793,786; 11,793,786 family; 12,268,664; 12,521,400) are assigned to Neurelis. No third party has ever appeared on the assignee side other than the secured lender.

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Timeline diagram

timeline
    title Ownership of US 12324852
    2008 : Family provisional filed
    2011 : Priority date 14 June
    2021 : Application 17 336389 filed
         : Orbimed security interest recorded
         : Inventors assign to Hale BioPharma
         : Hale BioPharma assigns to Neurelis
    2024 : Orbimed security interest released
         : First Delaware suit filed
    2025 : Patent US 12324852 B2 issued
         : Later Delaware suits filed
    2026 : Further Delaware suit filed

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NPE / troll‑pattern signals

1. Shell‑entity transfer — NOT PRESENT. The chain runs Hale BioPharma Ventures, LLC → Neurelis, Inc. (recorded 2021‑12‑13, reel/frame unverified). Hale BioPharma is a life‑sciences incubator associated with named inventor David F. Hale, not a "…IP / Patents / Licensing / Holdings" assertion vehicle; Neurelis is the NDA holder for VALTOCO and manufactured/marketed the product. No single‑purpose Delaware or Texas LLC appears anywhere on the assignee side. The only third party on the chain is a secured lender, which is the opposite of a shell transfer.

2. Known asserter in the chain — NOT PRESENT. Neither Hale BioPharma Ventures, Neurelis, Inc., nor Aegis Therapeutics, LLC appears on the Acacia / Marathon / Intellectual Ventures / IPNav / Wi‑LAN / Mosaid‑Conversant / Vringo / Pendrell / Innovatio / MPHJ / Lumen View / Round Rock / Erich Spangenberg lists, nor is any of them surfaced as a high‑frequency plaintiff in Unified Patents or RPX asserter directories by anything I retrieved. The litigant here is the product company, suing ANDA filers.

3. Repeat correspondent across the chain — UNCLEAR / NOT ESTABLISHED. This is the signal I most wanted and could not close. The retrieved sources do not expose the correspondent of record for any of the four recordings, and the only legal‑professional name that surfaces in the family (Troutman Pepper Hamilton Sanders LLP, on the face of sibling US 11,241,414) is prosecution counsel, not a recording correspondent. A single firm appearing once is expressly not a finding under the stated standard, and I have zero occurrences — so: unclear, no finding. To close this, query Assignment Center by patent number 12324852 and pull the correspondent field on each record.

4. Cascading transfers — NOT PRESENT. Exactly one substantive ownership movement (Hale BioPharma → Neurelis) plus one security interest and its release. Two of the four events are the same‑day perfection pair (2021‑12‑13) and two are the grant/release of a single financing (2021‑08‑06 / 2024‑11‑14). No chained LLC cascade, no <24‑month multi‑hop sequence, no shared correspondent address across assignees.

5. Pre‑litigation transfer — NOT PRESENT. The ownership transfer was recorded 2021‑12‑13; the first suit naming this patent is Neurelis, Inc. v. Padagis LLC, D. Del. 1:24‑cv‑00562, filed 2024‑05‑08 — roughly 29 months later, and triggered by Padagis's March 26, 2024 Paragraph IV notice letter, not by a venue‑engineering assignment. No assignment is dated within 6 months before any suit. (The family‑level Reel 048271/0304 recording predates the 2019 Aquestive IPRs, but that is ordinary standing hygiene by an operating owner, and it is not this patent.)

6. Bankruptcy fire‑sale — NOT PRESENT. Neurelis is an operating company with an approved NDA and an active royalty facility that was released (2024‑11‑14), not foreclosed. No Chapter 7/11, no §363 sale, no bankruptcy court involvement.

7. Privateering — NOT PRESENT. Privateering requires an operating company to hand assertion to a third‑party NPE. Here the operating company keeps and asserts the patent itself: Neurelis is the plaintiff in 1:24‑cv‑00562 (Padagis), 1:25‑cv‑01228, 1:25‑cv‑01443 (Lupin) and 1:26‑cv-00261, and is the patent owner of record in the parallel IPRs (Padagis IPR2025‑00464/‑465/‑466). No NPE was interposed.

8. Defensive aggregator — NOT PRESENT. The chain terminates at Neurelis, Inc., an operating drug company. No RPX, AST, LOT Network, Unified Patents or OIN participation appears.

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Verdict

Operating-company assertion.

Neurelis, Inc. is the assignee of record (Hale BioPharma Ventures, LLC → Neurelis, recorded 2021‑12‑13; family corroboration at Reel 048271, Frame 0304 for US 9,763,876) and it ships a product embodying the claims — VALTOCO® diazepam nasal spray under NDA No. N211635, with '852 Orange Book‑listed and expiring 2032‑10‑16. It is asserting this patent against actual competitors seeking generic entry, Padagis (D. Del. 1:24‑cv‑00562, filed 2024‑05‑08) and Lupin (1:25‑cv‑01443), each triggered by Paragraph IV notice letters rather than by a manufactured pre‑suit transfer. Every one of the eight NPE signals is absent or unclear, and the only third‑party interest ever recorded against the patent was a lender's security interest (Orbimed Royalty & Credit Opportunities III, LP, recorded 2021‑08‑06 and released 2024‑11‑14) — the signature of a revenue‑financing, not a troll chain.

One open item. Signal 3 (repeat correspondent) could not be scored, because the retrieved sources do not expose the correspondent field. Verify at the USPTO Assignment Center:

• https://assignmentcenter.uspto.gov/ (search patent number 12324852)
• https://assignment.uspto.gov/patent/index.html

If all four recordings show the same correspondent attorney/firm, that alone still would not convert an operating‑company assertion into an NPE verdict — but it would be worth recording, and it is the only thread here I have not pulled.

I'll search for the patent's cited references and front-page prior art listings.

The first search surfaced a PTAB filing containing a "References Cited" list, but for sibling patent '786/'414 — I need the '852 patent's own front-page citations. Let me dig further.

I need the front-page "References Cited" section for the '852 patent specifically. Let me try several angles.

Prior-Art Analysis — US 12,324,852 B2

0. Verification status (read this first)

I must flag a sourcing limit before giving any citations, because it materially affects confidence:

• The authoritative full text of US 12,324,852 that I was given is truncated. It ends partway through the specification and contains neither the claims nor the front-page "References Cited" section. So I cannot quote the '852 patent's own cited-art list from the source of record.
• My searches did not return the '852 patent's own front-page citation list. The Wayback/Google scrape returned the family's forward citations ("Cited By") and "Families Citing this Family," not the '852's backward citations.
• What I did retrieve is a PTAB petition exhibit reproducing the front page "References Cited" of the sibling patents US 11,793,786 B2 / US 11,241,414 B2 (same inventors, same family, same title). URL: https://ptacts.uspto.gov/ptacts/public-informations/petitions/1557269/download-documents?artifactId=X_OW7RIOpuwZrL1p_QbSDEqlfsrAGtojZxopVq7qABEX0cfycH8SoDQ

Consequence: everything below is (a) verbatim from the authoritative '852 text I was given, (b) from the sibling-patent front page just cited, or (c) from search results — and each is labeled as such. I have not fabricated a '852-specific citation list. Where a citation is inferred rather than confirmed, I say so.

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1. Why the '852 claims are a hard § 102 target

The granted independent claims (verified verbatim from DrugPatentWatch's rendering, https://www.drugpatentwatch.com/p/patent-claims/12324852) are extremely narrow:

Claim 1 — "A method of treating bouts of intermittent and stereotypic episodes of increased seizure activity in an epilepsy patient… administering a single spray of 100 μL to one nasal mucosal membrane… of a pharmaceutical solution consisting of: 56.47 mg of vitamin E USP +/−5%; 10 mg of diazepam; 0.25 mg of dodecyl maltoside; 10.50 mg of benzyl alcohol +/−5%, and a sufficient quantity of ethanol; wherein administering the single spray… achieves 92.5% to 107.5% of the bioavailability of an equivalent dose of diazepam administered intravenously…"

Three legal points govern the whole § 102 analysis:

1. Anticipation requires every limitation in a single reference. A reference disclosing a benzodiazepine + tocopherol + alcohol nasal solution without the quantitative 92.5–107.5% IV-equivalence limitation, the 100 µL single-spray geometry, and the specific mg-scale recipe cannot anticipate. It can only support § 103.
2. "Consisting of" is closed. The claim-1 solution is closed to unlisted ingredients. A prior-art formulation containing even one additional material (e.g., a paraben, water, TPGS) does not literally anticipate.
3. Critical date. Google Patents lists the '852 priority date as 2011-06-14 (family also anchored by TheraRadar at 2008-03-28). Because this application was filed 2021-06-02, the priority question is dispositive: if the claims are not supported by the 2011 disclosure (a real risk — the 2011 application described the broad "30–95% tocopherol" genus, whereas the claims recite Valtoco-specific clinical data), the effective filing date collapses to 2021-06-02, and the family's own 2012–2019 publications become available § 102(a)(1) prior art. This is the single highest-value § 102 theory against the '852 patent.

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2. Tier 1 — The references that actually matter for § 102

These are the family's own earlier publications. They are only prior art if the '852 claims lose their 2011 priority claim.

Sibling patents as § 102(a)(2) art — a nuance worth flagging: US 11,241,414 B2 (issued 2022-02-08), US 11,793,786 B2 (2023-10-24), US 12,268,664 (2025-04-08) and US 12,337,061 (2025-06-24) are all in the same family. They are ordinarily excepted from § 102(a)(2) by the § 102(b)(2)(A) (obtained-from-inventor) and (b)(2)(C) (common ownership) exceptions. Note a wrinkle I cannot resolve: the assignment record shows the Hale Biopharma → Neurelis assignment executed 2021-12-13, i.e., after the '852 filing date of 2021-06-02. § 102(b)(2)(C) requires common ownership "not later than the effective filing date," so a challenger could argue the exception is unavailable for the gap period. I flag this as an open question, not a conclusion.

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3. Tier 2 — The front-page "References Cited" of the sibling patents

The PTAB exhibit reproduced this U.S.-patent-documents list (I quote the numbers as extracted; the dates in that OCR are visibly garbled — e.g., it renders US 3,102,116 as "12/1962" when the patent issued in 1963 — so I am not certifying these dates). Subject matter in the right-hand column is corroborated against the '852 specification's own cross-references, which is authoritative.

Assessment: this list reads as a chemistry/formulation-art list accumulated across the family's prosecution — benzodiazepine synthesis patents plus nanoparticle and excipient patents. Not one of them is a nasal benzodiazepine spray achieving 92.5–107.5% IV bioavailability, so as a group they do not anticipate claims 1, 6, 10 or 14. They were presumably cited for § 103 and for enablement of the specification's synthetic routes.

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4. Tier 3 — Specification-incorporated and prosecution references

4.1 Patents the '852 specification expressly incorporates (authoritative text)

• US 6,193,985 — Vitamin E TPGS. Cited in the '852 spec. in the passage explaining that the carrier "specifically excludes synthetic tocopherols having a polymer glycol covalently bonded or linked to a tocopherol core, such as Vitamin E TPGS, which is described in U.S. Pat. No. 6,193,985."
  • § 102 potential: none against claims 1/6/10, and arguably teaching away. The claims recite "vitamin E USP," and the spec. affirmatively excludes TPGS. A reference the patent disclaims cannot anticipate the claim that excludes it.
• US 5,661,130 — alkyl glycosides (Intravail® family chemistry, dodecyl maltoside). Cited in the '852 spec. as the source of the alkyl-glycoside definition.
  • § 102 potential: none. It discloses only the penetration enhancer (0.25 mg dodecyl maltoside), never the diazepam/vitamin E/benzyl alcohol/ethanol solution, the 100 µL single metered spray, or the IV-equivalence. It supplies one means-plus-function element at most — a § 103 reference.
• US 3,987,052 (alprazolam), US 3,296,249 (lorazepam), US 3,243,427 (medazepam), US 3,722,371 (mexazolam), US 4,280,957 and US 5,831,089 (midazolam), US 3,567,710 and US 3,299,053 (flurazepam), US 3,340,253 and US 3,374,225 (temazepam), US 3,102,116 / 3,109,843 / 3,136,815 / 3,371,085 (diazepam) — all cited in the '852 spec. as manufacturing processes for the respective benzodiazepines.
  • § 102 potential: none. They disclose active-ingredient synthesis, not nasal administration. They are cited for enablement under § 112.

4.2 References appearing in the family's prosecution (from the PTAB petition, ptacts.uspto.gov/.../petitions/1522096)

• U.S. 2006/0046962 A1 ("Meezan") — alkyl glycosides as penetration enhancers. Cited as the secondary reference in § 103 rejections ("Claims 46, 47, 49 and 50 were rejected under 35 U.S.C. § 103(a) as being unpatentable over Sonne in view of Meezan").
  • § 102 potential vs. '852 claims: none. Discloses an enhancer class only.
• "Sonne" — relied on by the Examiner for the teaching that tocopherols/tocopherol derivatives are usable as drug carriers and that "due to the small administration volume required… a high concentration of the oil (or lipid) phase is required" for nasal administration; the petition also cites "European Patent Application No. 539,215 of Stafford-Miller" as a vitamin-E-as-penetration-enhancer teaching.
  • § 102 potential vs. '852 claims: none. The applicant's own submissions in that petition (which I retrieved) establish that Sonne is "entirely silent with respect to treatment of a patient having a seizure disorder" and teaches away from alcohol-containing mucosal solutions. I could not verify Sonne's full bibliographic citation (number, filing and publication dates) from my searches, and I will not guess at it.
• EP 2 152 274 A4 / Questor Pharmaceuticals, "Nasal administration of benzodiazepines" (priority 2007-05-07) — appears in Google Patents' family listing (patents.google.com/patent/US8895546B2/en). Its 2007 priority predates the family's 2008/2011 anchors, so it is chronologically capable of being prior art.
  • § 102 potential: plausible but unverified. I retrieved only the title and priority date; I have not read its disclosure and cannot state which '852 claim, if any, it anticipates. Flagged as the single most important reference to verify from a source I could not reach.

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5. Bottom line on § 102

1. On the reference list I was able to retrieve, no reference anticipates any claim of US 12,324,852. The list is dominated by benzodiazepine-synthesis and nanoparticle/excipient patents that cannot meet the "single 100 µL spray," "consisting of 56.47 mg vitamin E USP / 10 mg diazepam / 0.25 mg dodecyl maltoside / 10.50 mg benzyl alcohol" and "92.5–107.5% of IV bioavailability" limitations.
2. The genuine § 102 exposure is self-inflicted, not external: it is the family's own earlier patents and publications — US 8,895,546 B2 (2014), US 9,763,876 B2 (2017), US 2017/0196884 A1 (2017), WO 2012/174158 A2 (2012) — and it only materializes if the '852 claims are denied their 2011-06-14 priority date. That is exactly the priority/written-description vulnerability being pleaded in the Delaware ANDA actions, so the two analyses are the same analysis.
3. § 102(a)(2) via sibling patents (11,241,414; 11,793,786; 12,268,664; 12,337,061) is theoretically available but likely foreclosed by the § 102(b)(2) exceptions — subject to the 2021-12-13 assignment-timing wrinkle noted above.
4. Do not auto-correct anything: the '852 specification's internal quotation renders benzodiazepine "R₁–R₅" substituents and the figure list with obvious OCR artifacts (e.g., "zazepam" for "temazepam"), and the sibling front-page date column is garbled. I have preserved the identifiers as-found and refused to normalize the dates.

What I could not verify (explicit)

• The '852 patent's actual front-page "References Cited" list (the authoritative text I was given omits it entirely).
• Full bibliographic details (filing/publication dates) for "Sonne."
• The disclosure content of EP 2 152 274 (Questor) and therefore its anticipation scope.
• Issue dates in the sibling front-page table, which the PTAB OCR garbled.

If you want a defensible § 102 opinion, the next step is to pull the printed front page of US 12,324,852 from USPTO Patent Center and confirm the citation list against the sibling list I reproduced above. I am not able to certify that the two lists are identical.

I'll ground this § 103 analysis with a few targeted searches on the key secondary references, then build the combinations.

I have strong grounded material now. Let me confirm the '852 claim set and the Valtoco PK data point before drafting.

Obviousness Analysis Under 35 U.S.C. § 103 — US 12,324,852 B2

Builds on: the Patent Summary, Litigation, PTAB, Assignment, and Prior Art sections of this page. Those sections are incorporated by reference; I do not repeat them except where I must contradict or extend them.

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0. Two corrections/extensions to the prior sections before I begin

(a) The claim text is no longer second-hand. The claim-summary section flagged that the claims were unavailable in the authoritative text and that claims 6 and 10 were truncated. Two independent sources now give verbatim claim text: the DrugPatentWatch claim rendering (drugpatentwatch.com/p/patent-claims/12324852) and the Paragraph IV counterclaims in Neurelis v. Padagis (D. Del. 1:25-cv-01228) and Neurelis v. Lupin (D. Del. 1:25-cv-01443), which reproduce claim 1 word-for-word. Claims 1, 6 and 10 are confirmed; only the excipient amounts inside claims 6 and 10 remain elided in the public rendering. Claim 14 remains truncated and I still cannot characterize it.

(b) A materially new fact that changes the entire § 103 picture — the '852 claims are the '876 disclosure re-cast. The specification and claim set of US 9,763,876 B2 — the family ancestor whose 36 claims were held entirely unpatentable in IPR2019-00451 and affirmed on appeal — contain:

• Table 11-1 — the intranasal diazepam solution (the Valtoco formulation),
• Table 11-3 — the PK data: diazepam nasal spray 10 mg/100 µL vs. IV 5 mg, with Cmax 272 ng/mL and Tmax 1.50 h (0.8, 4.0),
• the express statement that the solution "was further found to have similar bioavailability to intravenous administration of diazepam (96% of i.v.)," and
• the express range "about 92.5 to 107.5% that obtained with the same benzodiazepine administered intravenously,"
• claim 28: "wherein the solution consists of about 56.47% (w/v) vitamin E, about 10.5% (w/v) benzyl alcohol, about 10% (w/v) diazepam, about 0.25% (w/v) dodecyl maltoside, q.s. dehydrated ethanol," and
• claim 36: "wherein said treatment achieves bioavailability that is from about 92.5 to 107.5% that obtained with the same benzodiazepine administered intravenously."

Source: US 9,763,876 B2 printed specification, cols. 63–66 (patentimages.storage.googleapis.com/.../US9763876.pdf).

That is the operative insight for this memo: the numerical limitations the '852 patent relies on for its novelty — the 56.47/10.5/10/0.25 mg recipe and the 92.5–107.5% IV-bioavailability window — were not merely disclosed in the prior art; they were the subject of dependent claims that the Board held obvious over Gwozdz + Meezan and that the Federal Circuit affirmed. I return to this in ¶ 6.

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1. The claim to be analyzed

I take claim 1 as representative. Its limitations divide cleanly into four groups:

Claims 6 and 10 vary only Group B (7.5 mg and 5 mg diazepam) and, for claim 6, Group C (one 100 µL spray to each nostril). Dependents 2/7/11 (96% BA), 3/8/12 (Tmax ≈ 1.5 h), 4/9/13 (substantially free of water) and 5 (single metered spray) add nothing new to Groups A–D.

Legal consequence of the drafting: every limitation in Groups D(ii)–(iii) is a statement of result, not a step. There is no claim element requiring the POSITA to do anything to "achieve 92.5%–107.5%," to "be safe and effective," or to "reduce seizure frequency." Those outcomes either follow inherently from performing Groups B + C in the recited patient, or they do not occur at all. That structure drives most of the analysis below.

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2. Level of ordinary skill in the art (POSITA)

Drawn from the expert testimony of record in this family (Dr. Peppas and Dr. Wermeling for Aquestive in IPR2019-00451; the Padagis expert in IPR2025-00465, whose opinions are quoted in the petition record):

A POSITA as of the relevant date would hold an advanced degree (M.S. or Ph.D.) in pharmaceutics, pharmaceutical chemistry, formulation science or pharmacology, or a bachelor's degree in one of those fields plus several years of hands-on experience developing nasal and other mucosal drug-delivery formulations, and would be familiar with (i) the use of tocopherols/vitamin E as non-aqueous solubilizing vehicles, (ii) penetration enhancers generally and alkyl glycosides specifically, (iii) nasal metered-spray device volumes and dosimetry, and (iv) the clinical management of epilepsy and seizure emergencies including rectal diazepam (Diastat®).

Two consequences: the POSITA is a formulator, not a clinician — so the "treating an epilepsy patient" preamble is routine; and the POSITA's toolbox expressly includes enhancer selection, co-solvent optimization, and spray-volume/dose concentration matching.

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3. Limitation-by-limitation mapping of the art

The mapping is strikingly complete. Once Gwozdz supplies A, B(diazepam/vitamin E/alcohols) and C', Meezan supplies the one missing excipient, and Cartt '784 supplies C, there is no residual limitation in claim 1 that is not either (i) disclosed, (ii) an obvious design parameter, or (iii) an inherent/predictable result.

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4. Ground 1 — Gwozdz + Meezan (the primary ground)

Combination: WO 2009/120933 (Gwozdz) in view of US 2006/0046962 (Meezan).

Why a POSITA would combine them — four independent motivations:

1. Gwozdz supplies the motivation in its own text. Gwozdz expressly contemplates adding further excipients, including penetration enhancers, to its tocopherol/alcohol solvent system. KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007) — an express suggestion in the primary reference is the paradigm case.
2. Meezan is in the same field and addresses the same problem. Meezan discloses alkyl glycosides, including n-dodecyl β-D-maltoside, as intranasal absorption enhancers, and per the IPR2019-00451 FWD it "is not limited to water soluble therapeutic drugs and discloses using alkyl glycosides in aqueous or non-aqueous systems." It also refers to small organic molecules and anti-seizure agents, which encompass benzodiazepines. The KSR "familiar elements according to known methods" rationale applies directly.
3. The problem Gwozdz leaves open is precisely the problem Meezan solves. Gwozdz solved solubility; it says nothing about maximizing permeation of the dissolved drug across the nasal mucosa. The POSITA's objective is a rescue product with plasma exposure matching IV — an object that both references frame. Dr. Wermeling's credited testimony (FWD, IPR2019-00451): "a POSA would understand the benefits from using a penetration enhancer, even in situations of already-high bioavailability, as penetration enhancers would… be useful in adjusting the rate and amount of drug absorbed purely intranasally."
4. Predictability. Adding a non-ionic, water-dispersible alkyl glycoside at 0.25% (w/w) to a non-aqueous co-solvent solution is a routine excipient-selection step with a known direction of effect (increased mucosal absorption) and no expected adverse interaction with the drug, the vehicle, or the spray device.

Expectation of success: high. The petitioner in the sibling proceedings catalogued the enhancer literature (EMS, Ex. 1019) and the PO's own specification does not identify any unpredictability — it simply recites that "the amount of alkyl glycoside… is selected so as to enhance absorption… while at the same time not significantly irritating the nasal mucosa."

Teaching-away, and why it fails. The patent owner's best argument is that Gwozdz distinguishes itself from surfactant- and micelle-containing formulations and exemplifies a "maximized tocopherol" system, so a POSITA modifying it with a surfactant would undermine its purpose. That argument was made and rejected in IPR2019-00451: "we are not persuaded that a POSA would have been deterred from modifying the one specific example in Gwozdz cited by Patent Owner." The PO's related "solubility index" argument (that at 95:5 tocopherol:ethanol Gwozdz achieves only ~9 mg/100 µL, so there is "little room to modify") is a teaching-away argument that cuts against the patent: the '852 claims use 56.5% vitamin E (not 95%), which by the PO's own theory increases the available ethanol headroom and reduces the precipitation risk the PO complains of. The claim sits inside Gwozdz's design space rather than outside it.

Result: Ground 1 renders claim 1 obvious. It is the ground the Board accepted against the '876 claims, and the '876 claims recite the same formulation without the benefit of the narrower numeric and geometry limitations that (as ¶ 6 shows) were separately claimed and also held obvious.

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5. Ground 2 — Gwozdz + Meezan + Cartt '784 (US 2008/0279784 / EP 2152274)

Ground 1 alone leaves Group C (single 100 µL spray into one nostril) and Group A (the seizure-cluster patient population) to be argued as obvious design choices. Ground 2 closes both with a reference that is squarely on point.

Cartt '784 supplies:

• the spray volume and geometry — "metered sprays having volumes of less than 250 μl, preferably less than 150 μl, and ideally from 25 to 100 μl," with express instruction that a dose may be given "in one nostril, in both nostrils sequentially, or in one nostril, then the second nostril, and then the first nostril again (and, optionally, in the second nostril again)";
• the acute seizure indication — "acute relief from seizure to a patient within a short period after administering a benzodiazepine, such as diazepam, to the patient"; and
• the PK objective — a diazepam nasal formulation "capable of producing anticonvulsant effective blood plasma levels within a short period."

Motivation. Cartt '784 is not merely analogous art; it is the same technical problem statement — the passage beginning "Nasal preparations are generally administered in metered sprays having volumes of less than 250 μl…" appears verbatim in the '852 patent's own specification. A POSITA seeking to practice Gwozdz's nasal diazepam solution would consult the leading nasal-benzodiazepine disclosure to learn the appropriate delivery geometry, and Cartt '784 tells him exactly what volume (25–100 µL) and what nostrils.

Claim 6 specifically. Claim 6's two-spray/one-per-nostril limitation is literally Cartt '784's disclosed regimen, and was the subject of Ground 2 in IPR2019-00451 (Gwozdz + Meezan + Cartt '784, against claims 17–23 of the '876 patent, which included the one-nostril/both-nostril/first-then-second-then-first dosing claims). The Board credited the motivation. The '852 specification offers no reason the POSITA would have been deterred.

Why 100 µL in particular is obvious. The volume is not an independent variable here — it is dictated by concentration. Gwozdz teaches that the tocopherol:ethanol system dissolves diazepam at ≥8% and "approaching the 10% level." The clinical diazepam rescue dose is 10 mg (the '876/''852 texts themselves recite "about 1 mg to about 20 mg," preferably 2–10 mg). 10 mg ÷ 10% w/v = 100 µL. Cartt's ideal range is 25–100 µL. The claim's volume is therefore the arithmetic intersection of the two references. That is In re Aller routine optimization, and the result is a "practical range" of the kind In re Geisler holds unobvious only where criticality is shown — which it is not.

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6. Ground 3 — Gwozdz + Meezan + Cartt '784 + the '876 specification (the killer ground, subject to the priority caveat)

This is where the analysis becomes unusual, and it is the point I flagged in ¶ 0(b).

The proposition. The '852 patent is a method claim to administering the very solution, in the very volume, in the very patient, achieving the very PK figure, that US 9,763,876 disclosed in its specification (Tables 11-1, 11-3; FIGS. 1–3) and claimed in dependent claims 28 and 36 — claims the Board held unpatentable as obvious over Gwozdz + Meezan, affirmed on appeal.

Why this is dispositive if the '876 is available as art:

• The recipe is identical. '876 claim 28: "consists of about 56.47% (w/v) vitamin E, about 10.5% (w/v) benzyl alcohol, about 10% (w/v) diazepam, about 0.25% (w/v) dodecyl maltoside, q.s. dehydrated ethanol." '852 claim 1: "56.47 mg vitamin E USP ±5%; 10 mg diazepam; 0.25 mg dodecyl maltoside; 10.50 mg benzyl alcohol ±5%, and a sufficient quantity of ethanol." Same numbers, re-expressed per 100 µL spray.
• The bioavailability window is identical. '876 claim 36 recites "about 92.5 to 107.5%" of IV bioavailability; so does '852 claim 1. '876 claim 35 recites "about 90 to 110%," claim 34 "about 80 to 125%." The '852's window is a narrowing of a range already disclosed and claimed, in the direction of the reference point (IV = 100%). In re Woodruff / In re Geisler / Iron Grip Barbell Co. v. USA Sports, Inc., 392 F.3d 1317, 1322 (Fed. Cir. 2004) (overlap of ranges is prima facie obviousness) — the very authority the Padagis petition cited against the '414 claims.
• The 96% dependent claim is a quoted datum. '876 spec.: "similar bioavailability to intravenous administration of diazepam (96% of i.v.)" — literally the '852 dependent claims 2/7/11.
• The Tmax dependent claim is a quoted table entry. '876 Table 11-3: Tmax = 1.50 h — literally '852 dependent claims 3/8/12.
• The Board already rejected the "unexpected results / criticality" defense for these very numbers. The petitioner's expert in IPR2025-00465 opined, and the record reflects, that neither the '786 nor its priority specifications "provide any evidence of criticality or unexpected results with regard to the claimed types and amounts." The FWD in IPR2019-00451 cancelled all 36 claims of the '876 — including 28 and 36 — and the Federal Circuit affirmed.

Motivation. None is needed in the conventional sense: a reference that discloses a composition plus the measured PK performance of that composition plus the indication supplies every element. If a § 103 motivation is wanted, it is the "prior art is within the inventor's own disclosure" rationale — the POSITA reading the '876 is told the formulation works, is told the numbers, and is told it treats "a disorder such as is treated with Diastat® diazepam gel."

Availability — the caveat, stated honestly. Whether the '876 is § 102/§ 103 art against the '852 turns entirely on priority, and the two branches differ:

• If the '852's effective filing date is 2011-06-14 (the date Google Patents lists), the '876 (filed 2014-10-29, issued 2017-09-19) is not § 102(a)(1) art; its § 102(a)(2) availability depends on whether it was "effectively filed" under § 102(d)(2) as to the Tables 11-1/11-3 subject matter — which, if that subject matter first appeared in the 2014 application, it was not.
• If the '852's 2011 priority fails (a live risk: the '852 adds claim elements not demonstrably in the 2011 disclosure), the effective filing date collapses to 2021-06-02, and the '876 (2017), US 8,895,546 (2014), US 2017/0196884 (2017) and WO 2012/174158 (2012) all become § 102(a)(1) printed publications — a scenario the Prior Art section already identified as the highest-value theory.
• Separately, and independent of priority, the '876 FWD is powerful evidence of what a POSITA would have found obvious as of 2009–2011. Even if the '876 is not "prior art," its reasoning is directly probative of the Graham factual inquiries, and the Board's priority/inherency reasoning is a template.

Recommendation: this ground should be pleaded in the alternative and the priority chain for the Tables should be verified from the '852 file history before it is relied on. It is not a substitute for Grounds 1–2; it is a force multiplier on them.

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7. Ground 4 — Sonne + EP 539,215 (Stafford-Miller) + US 5,661,130 (alternative pedigree for Groups B)

If a tribunal were to find Meezan's aqueous-adjacent disclosure an imperfect fit for a non-aqueous system, the same result is reachable through an alternative triad:

• Sonne — relied on by the Examiner in this family's prosecution for the teaching that tocopherols are usable as drug carriers and that "due to the small administration volume required [for nasal dosing]… a high concentration of the oil (or lipid) phase is required." That is a direct, express motivation to use a high-concentration tocopherol vehicle at a small nasal volume — i.e., to arrive at 56.5% vitamin E in 100 µL.
• EP 539,215 (Stafford-Miller) — vitamin E as a nasal penetration enhancer; supplies the "vitamin E is doing something useful in the nose" teaching that bridges the carrier and enhancer roles.
• US 5,661,130 — the alkyl glycoside genus expressly incorporated into the '852 specification itself (it is the source of the specification's own definition of "alkyl glycoside"), supplying dodecyl maltoside as an alternative to Meezan.

Motivation: all three address nasal/mucosal delivery of poorly soluble drugs and the use of lipidic vehicles and glycosidic enhancers. KSR makes the combination obvious where each element is "a familiar element… according to known methods."

Caveat carried forward from the Prior Art section: I still have not verified Sonne's full bibliographic identity (number, filing and publication dates) from any primary source, and I will not fabricate it. Ground 4 should be treated as a secondary/backup ground until that citation is confirmed from the printed front page. Note also that Sonne was cited by the Examiner and overcome by the applicants during prosecution — the patent owner will characterize that as a teaching-away record. That is a fact to be developed, not assumed.

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8. Ground 5 — Ivaturi/Wermeling intranasal-diazepam PK art (for Group D(i) only)

If the patent owner succeeds in isolating the bioavailability limitation as the point of novelty, the art specifically addressing intranasal diazepam pharmacokinetics closes it:

• Ivaturi et al. (2009), "A pilot study assessing the bioavailability and pharmacokinetics of diazepam after intranasal and intravenous administration in healthy volunteers" — a 2009 human crossover study of IN vs. IV diazepam (pre-2011, hence available). Its reported finding that intranasal diazepam is rapidly absorbed and that the principal barrier was nasal tolerability/pain, not the feasibility of IV-comparable exposure, is a direct motivation to select a non-irritating vehicle and a mucosal enhancer — the precise design logic of the Valtoco solution.
• The comparative PK paradigm itself — IN dose vs. IV dose, AUC ratio as the endpoint — was the established study design in the field before 2011.

Motivation: a POSITA seeking to match Diastat (whose 87–172% AUC geometric CV was the acknowledged problem in the field — see Cloyd et al.) would necessarily benchmark against IV and would necessarily test enhancer/vehicle combinations to raise and narrow the ratio. The claimed 92.5–107.5% window is simply a statement that this program succeeded.

Caution: I have only secondary-source descriptions of the Ivaturi 2009 pilot; I have not read it. The reported 2013 Agarwal/Ivaturi data (97% IN solution vs. 67% IN suspension) post-date 2011-06-14 and are not available art on a 2011 anchor — but they are available if priority fails.

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9. Secondary considerations (Graham factor 4)

A defensible obviousness opinion has to state the patent owner's best case. Here it is.

What Neurelis will argue, and my assessment:

Bottom line on indicia: Neurelis has a credible commercial-success and copying story but a weak unexpected-results story on the current record, and its "FDA approval = nonobvious" framing is affirmatively undercut by its own Clinical Pharmacology Review. The strongest counter to the patent owner is not that no indicia exist, but that the unexpected-results evidence predates the '852 application and was already before the Board when it cancelled the '876 claims.

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10. What would defeat these grounds

Stated plainly, because an obviousness analysis that does not identify its own failure modes is not useful:

1. A successful written-description/priority defense coupled with genuine new data. If Neurelis can (a) hold a 2011 effective date, (b) show the '876 is therefore not art, and (c) put new, post-2011 evidence of criticality (e.g., that 56.47% vitamin E specifically is critical and that 56.47 ± 20% falls off a cliff in bioavailability) into the record, Ground 3 collapses and Grounds 1–2 face an unexpected-results argument without the '876 FWD's contrary findings. The '852 specification as I have it contains no such criticality data.
2. Differentiation of Meezan. If the record shows Meezan's alkyl glycosides were understood to function only in aqueous systems (the PO made precisely this argument in IPR2019-00451), the Ground 1/2 motivation weakens for a "substantially free of water" claim. The Board rejected the argument in the '876 proceeding, and Meezan's own text says otherwise, but the argument is preserved.
3. Inherency dispute on Group D. If the tribunal treats "achieves 92.5%–107.5% of IV bioavailability" as a limitation that the prior art must be shown to inherently meet (rather than a result-effective variable to be optimized), the petitioner must prove the reference formulation inherently produces that ratio. Because Gwozdz discloses no in vivo human PK data, the petitioner would need to rely on the '876 data — which loops back to the priority question.
4. My own sourcing gaps. I have not read Gwozdz, Meezan, Cartt '784 or Sonne in full; I have read quotations and characterizations from the IPR2019-00451 FWD, the Padagis petition record, and the references' abstracts/specifications as retrieved. Passages I attribute to Gwozdz are quoted from the PTAB record's reproduction of Ex. 1009/EX1014, not from the WO publication itself. Verify against the primary documents before relying on any quotation in a filing.

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11. Conclusion

Claims 1, 6 and 10 of US 12,324,852 are, on the art identified in the Prior Art section, obvious under § 103. The strongest single ground is Gwozdz (WO 2009/120933) + Meezan (US 2006/0046962), in further view of Cartt '784 (US 2008/0279784 / EP 2152274) — the identical combination the Board accepted, and the Federal Circuit affirmed, against all 36 claims of the family's US 9,763,876.

Four points carry the analysis:

1. Gwozdz discloses every element but one — the nasal diazepam solution, tocopherol at 30–99% (w/w), ethanol + benzyl alcohol, the 10% diazepam solubility target, and the non-aqueous single-phase objective. Meezan supplies the one missing element (n-dodecyl β-D-maltoside as an intranasal enhancer), and Gwozdz itself supplies the motivation to add it.
2. Cartt '784 supplies the administration geometry — 25–100 µL metered sprays, one nostril or both sequentially — using language that appears verbatim in the '852 specification itself, and the 100 µL volume is arithmetically forced by Gwozdz's 10% solubility ceiling and the art-recognized 10 mg rescue dose.
3. The result limitations carry no patentable weight independent of the composition and route. 92.5–107.5% IV bioavailability is a measured property of the reference solution (the family's own '876 Table 11-3 reports 96% of i.v. at 10 mg/100 µL and Tmax 1.5 h); "safe and effective" was established by the FDA by PK bridging, with no efficacy trials; and the outcome list reproduces the endpoints of the Diastat® indication that the art expressly benchmarks.
4. The two numerical limitations that the '852 patent treats as its novelty were themselves claimed, and cancelled as obvious, in the '876 patent — claim 28 (56.47%/10.5%/10%/0.25%, q.s. ethanol) and claim 36 (92.5–107.5% of IV). That is the most consequential fact in this analysis, and it is new relative to the prior sections of this page.

The pivot point for any actual challenge is priority, not chemistry. If the '852 holds a 2011-06-14 effective filing date, Grounds 1–2 carry the case on Gwozdz + Meezan + Cartt '784 alone. If the 2011 priority fails, the family's own 2012–2017 publications become § 102(a)(1) art and the '852 is, on its face, obvious over its own ancestors — the outcome the Board already reached once in IPR2019-00451.

(Date note: the task framing states April 26, 2026; the system context and several retrieved sources carry stamps through July–August 2026. Nothing in this § 103 analysis turns on the current date — only on dates on or before the '852's effective filing date — but the discrepancy flagged in the Litigation section persists.)