US 8895546

Summary: U.S. Patent No. 8,895,546 B2 (US 8,895,546 / "the '546 patent")

Sources searched: USPTO/PTAB records (IPR2025-00464 and related filings), Google Patents, DrugPatentWatch, Docket Alarm/P-TACTS documents, and general web. I searched specifically for "8895546" and did not substitute similar numbers. I found no CAFC docket entry for this specific patent number as of the current date (April 26, 2026) — details below.

Bibliographic data (high confidence, corroborated by USPTO/PTAB records)

• Title: Administration of benzodiazepine compositions
• Patent/application numbers: US 8,895,546 B2; Appl. No. 13/495,942 (confirmation no. 7399; Patent Center no. 73828315)
• Filing date: June 13, 2012 (utility, nonprovisional under 35 U.S.C. § 111(a))
• Issue date: November 25, 2014
• Inventors (as printed): Steve Cartt (San Carlos, CA); David Medeiros (South San Francisco, CA); Garry Thomas Gwozdz (Jim Thorpe, PA); Andrew Loxley (Philadelphia, PA); Mark Mitchnick (East Hampton, NY); David Hale (San Diego, CA); Edward T. Maggio (San Diego, CA)
• Original assignee (at grant): Hale BioPharma Ventures, LLC (Encinitas, CA). Current assignee: Neurelis, Inc. (assigned Feb. 7, 2019). Google Patents lists "Neurelis Inc" as current assignee.
• Priority lineage: Continuation-in-part of U.S. Appl. 12/413,439 (filed Mar. 27, 2009, pub. US 2009/0258865); claims benefit of provisional applications 61/040,558 (filed Mar. 28, 2008), 61/497,017 (filed Jun. 14, 2011), and 61/570,110 (filed Dec. 13, 2011). Note: the patent's own cross-reference states the '558 provisional was filed Mar. 28, 2008; some IPR papers refer to it as Mar. 27, 2008 — a minor discrepancy I cannot fully resolve.
• Exemplary/independent claim count: Patent front page states "22 Claims, 5 Drawing Sheets." Primary Examiner: Adam C. Milligan. Prosecution counsel: Wilson Sonsini Goodrich & Rosati.
• Abstract: "The invention relates to pharmaceutical compositions comprising one or more benzodiazepine drugs for nasal administration, methods for producing and for using such compositions."
• Commercial context: Orange Book–listed and protects VALTOCO (diazepam nasal spray, 10 mg/spray), which was FDA-approved January 2020 (per IPR filings).

Plain-language overview of the independent claim

The only independent claim I can confirm from the granted patent record (claim 1, as reproduced in the IPR2025-00464 record and secondary sources) is a composition claim:

Claim 1 — A nasal benzodiazepine solution. A pharmaceutical solution for nasal administration consisting of four components only:
(a) a benzodiazepine drug (e.g., diazepam-type compounds);
(b) one or more natural or synthetic tocopherols or tocotrienols (Vitamin E-type compounds) in an amount of about 30% to about 95% (w/w);
(c) ethanol and benzyl alcohol in a combined amount of about 10% to about 70% (w/w); and
(d) an alkyl glycoside (a sugar-alkyl absorption enhancer, e.g., dodecyl maltoside).

Plainly: a preservative/free, non-aqueous, single-phase liquid drug product for spraying into the nose, where the benzodiazepine is dissolved in a Vitamin E + ethanol/benzyl alcohol solvent system, plus an alkyl-glycoside permeation enhancer, with the "consisting of" language closing the formulation to other ingredients.

Uncertainty note on independent claims: I was able to verify only Claim 1 as an independent claim from the available claim text. The Google Patents "definitions" text in the provided patent document describes multiple method-of-treatment embodiments, which suggests the full 22-claim set may include method claims, but I could not confirm their exact text from an authoritative claim listing, and I did not find a second confirmed independent claim. Claims 2–13 shown in secondary sources are dependent claims refining the benzodiazepine identity (diazepam), tocopherol/tocotrienol identity, concentration ranges, and alcohol ratios. If you need the complete granted claim set verbatim, the authoritative source is the USPTO Patent Center record or the PTAB exhibit EX1001.

Critical status updates (as of early 2026 — important for anyone analyzing this patent)

• Statutory disclaimer (35 U.S.C. § 253): On January 2, 2026, patent owner Neurelis filed a disclaimer of claims 1–16 and 18–21 (Exhibit 2075 in IPR2025-00464). As a result, only claims 17 and 22 remain in the patent. These are dependent claims, both reciting dodecyl maltoside:
  • Claim 17: The solution of claim 1, consisting of diazepam, vitamin E, ethanol, benzyl alcohol and dodecyl maltoside.
  • Claim 22: The solution of claim 16, wherein the alkyl glycoside is dodecyl maltoside (claim 16 = alkyl glycoside at 0.01%–1% (w/w), now disclaimed).
• PTAB proceeding (IPR2025-00464): Padagis US LLC petitioned for IPR of claims 1–22; the Board instituted review of all challenged claims (Sept. 2025 decision). After the disclaimer, the IPR concerns only claims 17 and 22, challenged as obvious over Gwozdz-PCT (WO 2009/120933) in view of Meezan (US 2006/0046962). Final written decision was projected for September 17, 2026; PTAB trial scheduled June 16, 2026. Related IPRs: IPR2025-00465 ('414 patent) and IPR2025-00466 ('786 patent).
• District court: Neurelis, Inc. v. Padagis LLC et al., 1:24-cv-00562 (D. Del.), involving the '546 patent; bench trial now scheduled March 1, 2027 (per Paragraph Four/ANDX tracking).
• CAFC 2026 dockets: I found no Federal Circuit appeal docketed in 2026 for this specific patent (8,895,546). The related family patent 9,763,876 was held unpatentable in IPR2019-00451, and that decision was affirmed by the Federal Circuit under Fed. Cir. R. 36 — but that appeal concerns a different patent number, not 8,895,546. Any CAFC appeal from IPR2025-00464 would be premature before the Board's final written decision (projected late 2026).

Disclaimer on remaining uncertainty

The legal status, assignment history, and litigation dockets above come from live web sources (USPTO P-TACTS, PTAB DocketAlarm, Paragraph Four tracking, and secondary legal blogs) and are the most current information available to me. Where the sources conflicted with my training data, I followed the search results. The one point I could not authoritatively verify is the complete verbatim text of all 22 granted claims and whether any independent claim other than claim 1 exists; for that, the USPTO Patent Center record or PTAB Exhibit EX1001 would be the definitive reference.

Litigation Involving U.S. Patent 8,895,546 (the "'546 patent")

Based on searches of PTAB, Delaware district court, and patent-litigation tracking sources (all current as of late 2025 / early-to-mid 2026), the known litigation specifically involving U.S. Patent No. 8,895,546 is as follows.

1. District Court — Hatch-Waxman ANDA Litigation

Case: Neurelis, Inc. v. Padagis LLC, Padagis US LLC, and Padagis Israel Pharmaceuticals Ltd. (and later-joined Lupin entities)

• Jurisdiction / Court: U.S. District Court for the District of Delaware
• Case No.: 1:24-cv-00562-MN (Judge Maryellen Noreika)
• Filing date: May 8, 2024
• Plaintiff(s): Neurelis, Inc.
• Defendant(s): Padagis LLC, Padagis US LLC, Padagis Israel Pharmaceuticals Ltd.; Lupin entities (Lupin Inc., Lupin Ltd., Lupin Pharmaceuticals, Inc.) were later added/consolidated into the action (consolidation order dated Nov. 13, 2025; Padagis counterclaims docketed from related C.A. No. 25-1228).
• Subject matter: Hatch-Waxman action under 35 U.S.C. § 271(e)(2) arising from Padagis's ANDA No. 219320 (and Lupin's ANDA No. 220394) for generic versions of VALTOCO® (diazepam nasal spray). The complaint asserts the '546 patent (among others, including U.S. Patent Nos. 11,241,414 and 11,793,786, with later-added patents such as 12,268,664, 12,324,852, and 12,337,061).
• Status (as of the most recent docket entries in early 2026): Active. Claim-construction (Markman) hearing held Sept. 12, 2025; discovery ongoing; the case has been consolidated for all purposes with related Neurelis v. Padagis actions (e.g., 1:25-cv-01228); a bench trial is scheduled for approximately March 1, 2027.
• Sources: https://www.docketalarm.com/cases/Delaware_District_Court/1--24-cv-00562/Neurelis_Inc._v._Padagis_LLC_et_al/ ; https://www.drugpatentwatch.com/p/litigation/casename/index.php?query=Neurelis%2C+Inc.+v.+Padagis+LLC%7C1%3A24-cv-00562 ; https://paragraphfour.com/members/parryashford/activity/11704/ (tracker noting bench trial 3/1/27).

2. PTAB — Inter Partes Review

Case: Padagis US LLC et al. v. Neurelis, Inc.

• Tribunal: USPTO Patent Trial and Appeal Board
• Case No.: IPR2025-00464
• Petition filing date: January 17, 2025 (accorded filing date Jan. 17, 2025)
• Petitioner(s): Padagis US LLC (with related Padagis entities identified)
• Patent Owner: Neurelis, Inc.
• Subject matter: Challenge to claims 1–22 of the '546 patent as unpatentable (relying principally on the Gwozdz PCT publication and the Meezan publication, with arguments about collateral estoppel from the earlier related IPR2019-00451 involving the related '876 patent).
• Status: Instituted — the Board granted institution on September 16, 2025. Patent Owner's Response was filed January 5–6, 2026. Notably, Neurelis filed a statutory disclaimer on January 2, 2026, disclaiming claims 1–16 and 18–21 of the '546 patent (recorded in the IPR as Exhibit 2075), leaving only claims 17 and 22 at issue in the proceeding. Per a case tracker, trial/oral hearing is set for June 16, 2026; no Final Written Decision has yet issued (as of the latest available records).
• Sources: https://ipverse.greyb.com/ptab-web/cases/case-details/IPR2025-00464 ; https://gaeflexstaging-dot-docketupdate.appspot.com/cases/PTAB/IPR2025-00464/Padagis_US_LLC_v._Neurelis_Inc/09-16-2025-Board/Institution_Decision__DECISION_Granting_Institution_of_Inter_Partes_Review_35_USC_%C2%A7_314/ ; statutory disclaimer exhibit at https://gaeflexstaging-dot-docketupdate.appspot.com/cases/PTAB/IPR2025-00464/Padagis_US_LLC_v._Neurelis_Inc/01-05-2026-Patent_Owner/Exhibit-2075-Exhibit_2075___Statutory_Disclaimer/

Related matters (not direct assertions of the '546 patent — flagged for context)

• IPR2019-00451, Aquestive Therapeutics, Inc. v. Hale Biopharma Ventures, LLC / Neurelis — an earlier IPR challenging the related U.S. Patent No. 9,763,876 (the "'876 patent," a continuation in the same family). The Board found claims 1–36 of the '876 patent unpatentable (Final Written Decision Aug. 6, 2020), affirmed by the Federal Circuit under Rule 36. This does not directly involve the '546 patent, but it is repeatedly cited in the IPR2025-00464 record on estoppel/priority issues.
• Additional consolidated Delaware actions (e.g., Neurelis v. Padagis, No. 1:25-cv-01228, filed Oct. 3, 2025, adding the '852 and '061 patents; Neurelis v. Padagis/Lupin, No. 1:25-cv-00821, filed July 2, 2025, adding the '664 patent) — these largely concern later-issued family members rather than new '546 claims, though they are consolidated with 1:24-cv-00562, where the '546 patent is asserted.

Summary

• No litigation has concluded against the '546 patent as of April 2026: the Delaware ANDA case (1:24-cv-00562) is active with trial set for ~March 1, 2027, and IPR2025-00464 is instituted and pending (trial/hearing ~June 16, 2026), with no Final Written Decision yet reported.
• The '546 patent's scope has been narrowed during litigation by Neurelis's January 2026 statutory disclaimer of claims 1–16 and 18–21, leaving claims 17 and 22.

Caveats: Docket-status details (especially the exact set of patents asserted in the later-consolidated actions and any post-January 2026 events in IPR2025-00464) are based on the search results available to me; I did not find any CAFC appeal specific to the '546 patent, and I found no litigation against the '546 patent outside the District of Delaware and the PTAB.

Proceedings overview

The USPTO Open Data Portal feed in this prompt shows zero AIA trials on file for US 8,895,546, but that ingest is stale: USPTO/PTAB records surfaced by web search confirm one active Inter Partes Review — IPR2025-00464 (Padagis US LLC v. Neurelis, Inc.) — filed 2025-01-17, instituted 2025-09-16, and still in trial with a Final Written Decision due ~2026-09-16/17; no direct IPR on the '546 patent has yet produced a claim-invalidating FWD, but the patent owner has statutorily disclaimed claims 1–16 and 18–21 (filed 2026-01-02), leaving only the two claims "at issue" in the pending IPR, and the same Gwozdz + Meezan obviousness combination that is pending here already invalidated all 36 claims of the sister '876 patent in IPR2019-00451 (affirmed on appeal) — so the realistic defensive posture is: most of the patent is already gone by the patentee's own hand, and the two remaining claims sit in an instituted IPR built on estoppel-bound priority findings that killed the family's lead patent.

IPR2025-00464 — Padagis US LLC v. Neurelis, Inc.

• Type: Inter Partes Review
• Filed: 2025-01-17 (petition; Paper 2 date, consistent with sibling petitions IPR2025-00465/-00466)
• Status: Active — trial instituted (ODP structured data says "no proceedings on file," which is outdated). Institution granted 2025-09-16 (Paper 13); Scheduling Order entered 2025-09-17 (Paper 15); Patent Owner's Response filed (public redacted version docketed 2026-01-06, Paper 29); Patent Owner's Request for Panel Rehearing of the certificate-of-correction denial filed 2026-02-20 (Paper 37). FWD due on the statutory one-year clock, ~2026-09-16/17 — imminent as of today (2026-09-09).
• Judge panel: Not identified in the sources reviewed (do not have the panel APJ names for IPR2025-00464).
• Petition grounds: Obviousness under pre-AIA 35 U.S.C. § 103(a) of the challenged claims of the '546 patent over Gwozdz-PCT (WO 2009/120933 A2, published 2009-10-01) in view of Meezan (US 2006/0046962 A1, published 2006-03-02) — the same core combination that invalidated the family's '876 patent. The petition also pressed threshold issues: that Neurelis is collaterally estopped from claiming priority to the '558 provisional (2008-03-28), which is what makes Gwozdz § 102(e) prior art, and that Gwozdz itself is entitled to its '281 provisional filing date. Padagis is a defendant in parallel Hatch-Waxman litigation, Neurelis, Inc. v. Padagis LLC et al., 1:24-cv-00562 (D. Del.).
• Institution decision: Granted — 2025-09-16 (Paper 13). The panel held that collateral estoppel from IPR2019-00451 (where the Board, affirmed on appeal, found the near-identical alkyl-glycoside claims of the '876 patent unpatentable and not entitled to the '558 provisional priority date) bars Neurelis from re-litigating the '546 claims' entitlement to the '558 provisional date — making Gwozdz available as prior art. The panel declined, however, to apply collateral estoppel to Gwozdz's own priority date (that issue was not actually litigated in the '451 IPR), leaving that dispute open. Before institution, the Acting Director (decision dated 2025-07-16, later designated informative by Director Squires on 2026-01-09) rejected Neurelis's request for discretionary denial and referred the petition to the Board for a merits institution decision.
• Final Written Decision: Not yet issued. No claim has been canceled in this IPR as of 2026-09-09.
• Critical mid-trial event — statutory disclaimer: On 2026-01-02 Neurelis filed a statutory disclaimer (Exhibit 2075 in this IPR) disclaiming claims 1–16 and 18–21 of the '546 patent, which Patent Owner's own rehearing brief describes as "disclaiming all but the two patent claims at issue" — i.e., the two claims Padagis's petition actually put in play (claims 17 and 22 under the disclaimer's enumeration; flag: the full claim text/numbering was not in the materials I could verify, so confirm against the certificate/disclaimer record). Disclaimed claims are void and cannot be asserted going forward, and the PTAB will not issue a merits decision on them.
• Settlement / termination: None. The case is contested and active; the parties are litigating the § 103(c)(2) joint-research-agreement "safe harbor" question. The Board (Paper 36, ~February 2026) denied Neurelis leave to seek a certificate of correction that would add a JRA disclosure to the specification (which Neurelis argued would disqualify Gwozdz as obviousness art under pre-AIA § 103(c)(2)); Neurelis's request for panel rehearing (Paper 37, 2026-02-20) was pending as of the last docket activity I could confirm.
• Appeal: None yet — no FWD to appeal.
• Defensive value: High but incomplete. Claims 1–16 and 18–21 are already dead by the patentee's own disclaimer — any infringement theory built on them is a non-starter. The two remaining claims are the subject of an instituted IPR on grounds that already wiped out the identical family patent, with the priority question resolved against Neurelis by collateral estoppel; a defendant should expect those claims to be in serious jeopardy when the FWD lands (imminently).

Related family proceedings (context — not direct challenges to the '546 patent)

These do not count against the "proceedings on the '546 patent" tally but drive the current IPR and matter enormously for defense:

• IPR2019-00449, IPR2019-00450, IPR2019-00451 — Aquestive Therapeutics, Inc. v. Neurelis, Inc. (challenging US 9,763,876, a continuation of the '546 patent): -00449 and -00450 were denied institution; -00451 was instituted and produced a Final Written Decision on 2020-08-06 (Paper 44) holding all claims 1–36 of the '876 patent unpatentable as obvious over Gwozdz + Meezan (claims 17–23 additionally with Cartt '784), and finding the claims not entitled to the 2008-03-28 '558 provisional priority date. The PTAB Litigation Blog reports the FWD was affirmed by the Federal Circuit (CAFC docket number not identified in the sources reviewed). Panel in -00451: APJs Yang, Tornquist, and Wisz.
• IPR2025-00465 and IPR2025-00466 — Padagis US LLC v. Neurelis, Inc. (filed 2025-01-17): coordinated companion IPRs on family members US 11,241,414 and US 11,793,786 (the later, n-dodecyl-β-D-maltoside-limited continuations). Instituted on the same referral; the same informative Director decision (2025-07-16) covers all three Padagis IPRs.

Strategic summary

Claim status of US 8,895,546. No PTAB FWD has ever canceled a claim of the '546 patent directly, because IPR2025-00464 is still in trial. But the patent's practical claim map changed dramatically on 2026-01-02: the patentee disclaimed claims 1–16 and 18–21 under 35 U.S.C. § 253, leaving only the two claims "at issue" in the pending IPR (claims 17 and 22, per the disclaimer's enumeration — verify the certificate of disclaimer before relying on the exact numbers). Those two claims are currently being tested (instituted IPR, FWD due ~2026-09-16/17); every other claim is now unassertable, and the sister '876 patent's mirror-image claims are finally invalidated (IPR2019-00451, affirmed). The strongest statement a defendant can make today: the asserted scope of this patent family has already been condemned by the Board on the same Gwozdz + Meezan ground now pending against the surviving claims.

Estoppel landscape. Two separate estoppel strands matter. Petitioner-side (§ 315(e)(2)): Padagis — the current defendant in Neurelis v. Padagis, 1:24-cv-00562 (D. Del.) — is barred from re-raising in that district action any ground it raised or reasonably could have raised in IPR2025-00464, i.e., the Gwozdz + Meezan § 103 combination (and closely related variants). That bar does not bind a new defendant outside Padagis's privity. Patentee-side (collateral estoppel/issue preclusion): the Board has already ruled — with finality, now estoppel-bound in this very IPR — that the alkyl-glycoside claims of this family are not entitled to the 2008-03-28 '558 provisional priority date. That issue preclusion runs against Neurelis and is repeatable ammunition: any later defendant can use Gwozdz-PCT as § 102(e) art without re-litigating the priority fight. For a defendant facing a demand letter today, the still-open prior-art space is broad — Gwozdz + Meezan is the established killer combination, and the Board's priority finding makes it available; the § 103(c)(2) JRA safe-harbor escape route Neurelis is attempting has so far been rejected by the Board (certificate-of-correction leave denied, rehearing pending).

Pattern signals. This is a coordinated, multi-front campaign against the Neurelis Valtoco® (diazepam nasal spray) Orange Book portfolio, not a one-off: Aquestive filed three IPRs on the '876 continuation in 2019 (one succeeded, all claims invalidated, affirmed); Padagis filed three coordinated IPRs in 2025 on the '546 parent plus the '414 and '786 continuations, using the '451 FWD as a collateral-estoppel springboard. Neurelis's defense has been aggressive but increasingly cornered — it has tried discretionary denial (rejected, decision designated informative), priority arguments (estopped), a statutory disclaimer to narrow to two claims, and a late-breaking certificate-of-correction/JRA strategy (denied leave; on rehearing). The "informative" designation of the Acting Director's 2025-07-16 non-denial signals the Office views the Padagis IPRs as a proper use of resources — a bad sign for the patent owner. Notably, the Google Patents litigation metadata flags IPR2025-00464 as the only PTAB case against the '546 patent itself, corroborating that the ODP "no proceedings" feed is simply not yet ingesting this docket.

Recommended next steps

• Verify the disclaimer before drafting any invalidity or non-infringement position. Pull the recorded statutory disclaimer (filed 2026-01-02, acknowledgement receipt in IPR2025-00464 Ex. 2075) from the USPTO assignment/Patent Center records and confirm exactly which claims remain (the filing disclaims claims 1–16 and 18–21; confirm whether claim 22 exists and survives). If your demand letter cites any disclaimed claim, that theory is dead on arrival — respond by pointing to the § 253 disclaimer.
• Watch for the IPR2025-00464 FWD — due on or about 2026-09-16/17 (statutory one-year deadline from the 2025-09-16 institution; PTAB Scheduling Order entered 2025-09-17). Docket mirrors and Board filings are available at the PTAB case page (e.g., the docket mirror here and the Institution Decision, Paper 13, here). If the Board cancels the surviving claims, the patent is effectively a shell — quote the FWD's disposition verbatim in any motion to dismiss or summary judgment and move to moot the infringement case.
• If you are not Padagis (no privity), § 315(e)(2) does not bind you. You remain free to assert Gwozdz-PCT (WO 2009/120933) + Meezan (US 2006/0046962) under § 103, plus any other art; and because Neurelis is collaterally estopped from claiming the 2008 '558 provisional priority date for the alkyl-glycoside genus claims (per IPR2019-00451, FWD Paper 44, affirmed), you can establish Gwozdz's § 102(e) status without re-litigating that issue. The PTAB's rejection of Neurelis's JRA/certificate-of-correction gambit (Paper 36, rehearing pending as Paper 37) also tells you the § 103(c)(2) safe harbor is a weak counter that the Board has already viewed skeptically.
• If you are in the parallel Delaware litigation or a future ANDA case, consider moving to stay pending the IPR2025-00464 FWD (due within days), since the FWD will likely resolve the only surviving claims of the Orange-Book-listed '546 patent on grounds the Board has already endorsed once.
• Caveat on sources: the USPTO ODP feed in this prompt shows no proceedings (stale), and my document-level verification was limited to search snippets and docket aggregators (DocketAlarm, ipverse/GreyB, and the PTAB docket-update mirror). Confirm the FWD, any rehearing outcome, and the CAFC docket number for the '451 appeal directly in PTAB E2E / Patent Center and the Federal Circuit docket before citing them in a filing.

Inventors

Named inventors (as printed on US 8,895,546): Steve Cartt, David Medeiros, Garry Thomas Gwozdz, Andrew Loxley, Mark Mitchnick, David Hale, Edward T. Maggio.

Employers at filing, where determinable from public sources (application 13/495,942 filed 2012-06-13; all seven assigned to Hale BioPharma Ventures, LLC, recorded 2012-06-19 per Google Patents legal events):

• David Hale — founder/principal of Hale BioPharma Ventures, LLC (the named assignee); San Diego, CA. Confident.
• Edward T. Maggio — principal of Aegis Therapeutics, LLC (San Diego), the company behind the Intravail® alkyl-glycoside absorption-enhancer technology that claims (d) of claim 1 practice; his presence tracks the Hale/Aegis collaboration. Confident.
• Mark Mitchnick — also associated with Aegis Therapeutics / Intravail technology (East Hampton, NY address on the patent). Reasonably confident.
• Andrew Loxley — formulation scientist (Philadelphia, PA); specific employer at filing not verified. Unclear.
• Steve Cartt (San Carlos, CA), David Medeiros (South San Francisco, CA), Garry Thomas Gwozdz (Jim Thorpe, PA) — development/manufacturing roles; specific employers not verified. Unclear.

Pattern note: the inventorship is split between Hale BioPharma personnel (diazepam/Vitamin-E solvent formulation) and Aegis Therapeutics personnel (alkyl-glycoside enhancer) — a deliberate two-company collaboration reflected later in the record, when Aegis Therapeutics LLC appears alongside Neurelis as assignor on the 2021 OrbiMed security agreement and as co-owner on the 2024 release. This is not the "inventors flee within 12 months before a fire-sale" pattern; all inventors assigned at filing to the intended development entity.

Original assignee

Hale BioPharma Ventures, LLC (Encinitas/San Diego, CA) is the entity named on the issued patent (recorded assignment of inventors' interest 2012-06-19; patent issued 2014-11-25).

• Product shipped: No. Hale BioPharma was a development-stage specialty pharma. The product that practices the claims — VALTOCO (diazepam) nasal spray, 10 mg/spray — was FDA-approved January 2020, i.e., roughly 11 months after the patent family (including this patent) moved to Neurelis, Inc. (recorded 2019-02-07). So Hale BioPharma originated the product but did not commercialize it under its own name.
• Primary line of business: development of intranasal benzodiazepine products (diazepam rescue therapy for epilepsy), using the Intravail enhancer platform.
• Current status: the operating assets and the '546 patent sit with Neurelis, Inc.; I could not verify from my sources whether Hale BioPharma Ventures, LLC remains an active entity or was wound down post-2019 transfer.

Assignment timeline

I could not query USPTO Assignment Center directly in this session. The conveyances below are reconstructed from (i) Google Patents legal-event records for US 8895546 (reproduced in the authoritative patent text) and (ii) PTAB filings. Reel/frame numbers were obtainable only for the 2019 transfer, via patent-owner mandatory notices in the related IPR. Verify reel/frame and correspondents at the USPTO Assignment Center (https://assignmentcenter.uspto.gov) before relying on this in a filing.

• 2012-06-13 (executed, same-day filing) / recorded 2012-06-19 — Reel/frame: not retrieved

  • Conveyance: Assignment of Assignors' Interest (execution identical to filing date; standard at-issuance-of-rights recording)
  • Assignor: Steve Cartt, David Medeiros, Garry Thomas Gwozdz, Andrew Loxley, Mark Mitchnick, David Hale, Edward T. Maggio (all seven inventors)
  • Assignee: Hale BioPharma Ventures, LLC
  • Correspondent: not retrieved
  • Context: initial assignment of the pending application from inventors to the development company formed around them — an at-filing assignment, not an NPE transfer.

• 2019-02-07 (recorded) — Reel 048271 / Frame 0304 (per Neurelis' mandatory notices in IPR2019-00449/00451 for the related patent 9,763,876, filed Feb. 19, 2019; the Google Patents event for this patent shows the same assignor/assignee recorded 2019-02-07 — I treat reel 048271/0304 as covering this family transfer but could not confirm the '546 patent is on that exact document)

  • Conveyance: Assignment of Assignors' Interest
  • Assignor: Hale BioPharma Ventures, LLC
  • Assignee: Neurelis, Inc.
  • Correspondent: not retrieved
  • Context: consolidation of the VALTOCO program into the operating company ~11 months before FDA approval — an internal reorg/asset consolidation, not an arm's-length sale.

• 2021-08-06 (recorded) — Reel/frame: not retrieved

  • Conveyance: Security Agreement (security interest)
  • Assignor: Aegis Therapeutics, LLC; Neurelis, Inc.
  • Assignee: OrbiMed Royalty & Credit Opportunities III, LP
  • Correspondent: not retrieved
  • Context: debt financing / royalty securitization against the Neurelis asset base by a healthcare royalty investor (OrbiMed is a life-sciences investment firm, not an NPE); Aegis co-granting reflects its co-ownership stake.

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

  • Conveyance: Release by Secured Party
  • Assignor: OrbiMed Royalty & Credit Opportunities III, LP
  • Assignee: Aegis Therapeutics, LLC; Neurelis, Inc.
  • Correspondent: not retrieved
  • Context: release of the 2021 security interest, restoring unencumbered ownership to the operating company (and its co-owner affiliate).

That is the complete conveyance set I can substantiate: original inventors→Hale BioPharma (2012), Hale BioPharma→Neurelis (2019), OrbiMed security interest (2021), OrbiMed release (2024). No change-of-name, merger, or license conveyances were found.

Timeline diagram

timeline
    title Ownership of US 8895546
    2009 : Parent application filed
    2012 : Filed by Hale BioPharma
         : Inventors assign to Hale BioPharma
    2014 : Patent issued
    2019 : Assigned to Neurelis Inc
    2021 : OrbiMed security interest
    2024 : OrbiMed releases lien
    2026 : Claims disclaimed in IPR

NPE / troll-pattern signals

1. Shell-entity transfer — not present. Hale BioPharma Ventures, LLC (original assignee) was a development-stage originator, not a licensing-only shell, and it transferred to Neurelis, Inc., an FDA-regulated operating company. No "IP Holdings"-style licensing vehicle appears in the chain. No reel/frame contradicts this.
2. Known asserter in the chain — not present. Neither Hale BioPharma, Neurelis, Aegis Therapeutics, nor OrbiMed Royalty & Credit Opportunities III, LP appears on public NPE lists (Acacia, Marathon, IV, Conversant, RPX/Unified high-frequency-asserter directories). OrbiMed is a healthcare royalty lender; its interest was released 2024-11-14.
3. Repeat correspondent across the chain — unclear. I could not retrieve correspondent names for any reel/frame in this session (only reel 048271/0304 is known, and its correspondent was not captured in my sources). No recurrence finding can be made without Assignment Center access.
4. Cascading transfers — not present. Four conveyances over ~12 years, none chaining through a series of single-purpose LLCs; the 2021 and 2024 entries are a financing and its release, not ownership churn.
5. Pre-litigation transfer — not present. The only outright ownership transfer (Hale BioPharma → Neurelis, 2019-02-07, reel 048271/0304) predates the first suit naming this patent (Neurelis v. Padagis, 1:24-cv-00562, D. Del., 2024) by ~5 years. The 2024-11-14 OrbiMed release merely cleared a lender's lien around the time of that suit; it did not move the patent to a new asserting entity.
6. Bankruptcy fire-sale — not present. No insolvency proceedings involving any assignor were found.
7. Privateering — not present. Neurelis asserts in its own name against a generic entrant; there is no SEC/coverage evidence of an operating company hiding behind an NPE.
8. Defensive aggregator (anti-NPE) — not present. The chain terminates at Neurelis/Aegis, not at RPX, AST, LOT, Unified Patents, or OIN.

Verdict

Operating-company assertion.

Neurelis, Inc. — the current owner (recorded 2019-02-07; reel 048271/0304 per IPR mandatory notices) — is an FDA-licensed drug company that markets VALTOCO (diazepam nasal spray, approved January 2020), an Orange Book–listed product that practices the '546 claims, and it is asserting the patent against Padagis LLC, a generic competitor, in 1:24-cv-00562 (D. Del.), while defending IPR2025-00464 (in which it disclaimed claims 1–16 and 18–21 on 2026-01-02, leaving dodecyl-maltoside claims 17 and 22). That is the classic brand-vs-generic (Hatch-Waxman) assertion posture, and none of the eight NPE signals is present. The 2021 OrbiMed security interest and its 2024 release are routine healthcare royalty financing, not troll infrastructure.

Caveats: I could not directly query the USPTO Assignment Center, so reel/frame numbers and correspondent names for the 2012, 2021, and 2024 conveyances are unverified, and I could not confirm the '546 patent is listed on reel 048271/0304 (that citation comes from PTAB notices in the related 9,763,876 IPRs). Verify at: https://assignmentcenter.uspto.gov (search by patent number 8895546) before relying on this analysis.

I've reached the tool-call limit, so I'll answer now based on the verified information I gathered, with explicit flags where the full official USPTO "References Cited" list could not be retrieved within my available steps.

Prior Art Analysis — U.S. Patent No. 8,895,546 B2

1. Search disclosure and key caveats

What I searched. I searched Google Patents, PTAB records for IPR2025-00464 (Padagis US LLC v. Neurelis, Inc.), USPTO P-TACTS petition documents, Docket Alarm, and family/publication aggregators for the literal identifier 8895546 / US 8,895,546 B2. I did not substitute or auto-correct the number.

Important caveat — I could not retrieve the complete official USPTO front-page "References Cited" list in this session. The fetched Google Patents text for the '546 patent (provided in the task) does not reproduce the front-page citation field, and my searches surfaced only partial citation data. The authoritative source for the complete examiner-cited list is the USPTO Patent Center record for Appl. No. 13/495,942 or PTAB Exhibit EX1001/EX1004 in IPR2025-00464. Accordingly, the reference set below is representative and verified in part, not guaranteed exhaustive. I flag the confidence level of each item.

Claims relevant to a § 102 analysis (critical). As documented in the previously generated sections (verified via PTAB Exhibit 2075), patent owner Neurelis filed a statutory disclaimer on January 2, 2026 of claims 1–16 and 18–21. Only claims 17 and 22 remain, both directed to dodecyl maltoside:

• Claim 17 — the solution of claim 1, consisting of diazepam, vitamin E, ethanol, benzyl alcohol and dodecyl maltoside.
• Claim 22 — the solution of claim 16 (alkyl glycoside at ≥0.01% (w/w)), wherein the alkyl glycoside is dodecyl maltoside.

Because the application was filed June 13, 2012 (before the AIA's March 16, 2013 effective date) and claims priority to 2008–2009 applications, pre-AIA § 102 governs. The surviving claims are closed ("consisting of") composition claims requiring a dodecyl maltoside alkyl glycoside.

2. Prior art references identified

A. WO 2009/120933 A2 — "Gwozdz-PCT" / Hale BioPharma Ventures, LLC (highest-confidence, IPR primary reference)

• Full citation: Gwozdz, Cartt, Medeiros, Loxley, Mitchnick, Hale, Maggio (assignee Hale BioPharma Ventures, LLC), "Administration of benzodiazepine compositions," WO 2009/120933 A2, published ~Oct. 1, 2009 (week 40 of 2009); claims priority to U.S. Prov. 61/040,558 (Mar. 2008) and U.S. Appl. 12/413,439 (Mar. 27, 2009).
• Relationship to the '546 patent: This is the PCT publication of the '546 patent's own parent application (U.S. 12/413,439 → US 2009/0258865 A1). It was published more than one year before the '546's June 13, 2012 filing date, so if the surviving claims are not entitled to the 2008/2009 priority date, it is a printed publication under pre-AIA § 102(b) (and § 102(e) as a U.S.-filed application, subject to the same-inventor/commonly-owned considerations).
• Brief description: Discloses nasal pharmaceutical compositions/methods for benzodiazepines (including diazepam) dissolved in a carrier comprising tocopherols/tocotrienols (Vitamin E, ~30–95% w/w) together with one or more alcohols or glycols (e.g., ethanol, benzyl alcohol) — i.e., the same solvent system claimed in the '546 — and describes nasal administration for seizures.
• § 102 anticipation analysis: In IPR2025-00464, the Board instituted review of all challenged claims, and after the disclaimer the remaining ground challenges claims 17 and 22 as obvious over this reference in view of Meezan (below) — not as anticipated. Based on the reference set available, WO 2009/120933 does not appear to anticipate claims 17 or 22 standing alone, because the surviving claims require an alkyl glycoside that is dodecyl maltoside in a closed "consisting of" formulation; that specific limitation is the reason the petitioner needed the secondary Meezan reference. (Source: IPR2025-00464 institution papers, cited in prior sections; Google Patents family data.)

B. US 2006/0046962 A1 — "Meezan" (IPR secondary reference)

• Full citation: Meezan (spelling per IPR record), US 2006/0046962 A1, published Mar. 2, 2006 (publication number pattern); assigned to a non-Hale entity.
• Brief description: Cited by the IPR petitioner as teaching alkyl glycoside absorption/permeation enhancers (alkyl saccharides used to enhance intranasal drug absorption) — the knowledge gap the petitioner asserts is missing from WO 2009/120933 with respect to dodecyl maltoside.
• § 102 anticipation analysis: Because it is used in the IPR as a secondary reference for obviousness (combining with Gwozdz-PCT), it is not contended to anticipate claims 17 or 22 by itself. I could not verify its full disclosure text in this session, so I cannot rule out that portions alone read on sub-limitations (e.g., an alkyl glycoside enhancer), but the surviving claims require the full closed combination including the Vitamin E + ethanol/benzyl alcohol solvent system, which Meezan alone does not supply.

C. US 6,193,985 B1 — A/S Dumex (Dumex Ltd.) "Tocopherol compositions" (likely examiner-cited; incorporated in spec)

• Full citation: US 6,193,985 B1, filed May 16, 1994, issued Feb. 27, 2001, assignee A/S Dumex (Dumex Ltd.). Title per the CN family citation data: "Tocopherol compositions for . . . ." (verified partial). This is the Vitamin E TPGS (tocopherol-PEG-succinate) reference expressly incorporated by reference in the '546 specification ("described in U.S. Pat. No. 6,193,985").
• Brief description: Discloses tocopherol-based (Vitamin E TPGS) pharmaceutical carrier/suspension compositions. It appears in the Patent Citations list of the related CN family member CN103796656A (which shares priority with WO2012174158/US '546), corroborating that it was before the examiner.
• § 102 anticipation analysis: The '546 specification relies on this reference for the excluded TPGS-type tocopherol embodiments and for particulate suspensions — i.e., subject matter the surviving claims exclude ("consisting of" solutions, and embodiments excluding Vitamin E TPGS). It does not disclose the required diazepam + Vitamin E + ethanol/benzyl alcohol + dodecyl maltoside closed solution and is not believed to anticipate claims 17 or 22. Confidence: moderate that it appears on the face; based on family citation data plus in-spec incorporation.

D. US 5,661,130 A — alkyl glycoside absorption enhancer patent (Maggio) (incorporated in spec; likely cited)

• Full citation: US 5,661,130 A (inventor Maggio; assignee Aegis-affiliated), issued Aug. 26, 1997 (number pattern; issue year to be confirmed against Patent Center). The '546 specification states alkyl glycosides "as described in U.S. Pat. No. 5,661,130, which is incorporated by reference herein."
• Brief description: Foundational patent on alkyl glycosides (e.g., dodecyl maltoside) as intranasal absorption-enhancing agents — the very enhancer class required by surviving claims 17/22.
• § 102 anticipation analysis: Although it teaches dodecyl maltoside as an enhancer, it does not disclose the closed benzodiazepine/Vitamin E/ethanol/benzyl alcohol/dodecyl maltoside solution of claims 17/22, so it does not anticipate the surviving claims; at most it would be an obviousness component (consistent with the IPR's use of a Meezan-type alkyl glycoside reference). Confidence: high that it was before the examiner (in-spec incorporation); face-citation status unverified.

E. US 2009/0047347 A1 — Aegis Therapeutics (mentioned in spec)

• Full citation: US 2009/0047347 A1, published Feb. 19, 2009 (the '546 spec references an Aegis alkyl-glycoside/HLB publication "published on 19 Feb." 2009). Exact title/assignee not verified this session.
• Brief description: Referenced in the '546 specification for determining the hydrophile-lipophile balance (HLB) of suitable alkyl glycosides (HLB ~10–20, especially 11–15).
• § 102 anticipation analysis: A definitional/enabling reference for the alkyl glycoside selection; does not alone disclose the full claim 17/22 closed formulation and is not believed to anticipate. Confidence: moderate on relevance, low on face-citation status.

F. US 2009/0258865 A1 — the '546's own parent publication

• Full citation: US 2009/0258865 A1 (Hale BioPharma Ventures), published Oct. 15, 2009 (per Google Patents family metadata: "patent/US20090258865A1"), from Appl. 12/413,439 filed Mar. 27, 2009 — the parent of the '546 (CIP).
• Brief description: The published parent application disclosing the benzodiazepine/Vitamin E/alcohol nasal formulations.
• § 102 anticipation analysis: As the '546 is a continuation-in-part, the parent publication is prior art only against subject matter not entitled to the parent's priority date. This is the same priority question that drives the IPR's reliance on WO 2009/120933. If the dodecyl maltoside closed-claim subject matter of claims 17/22 was not disclosed in the parent, US 2009/0258865 A1 (and its PCT twin WO 2009/120933) are § 102(b) prior art. Whether it anticipates depends on whether the parent discloses the full closed combination with dodecyl maltoside; the IPR's decision to pair it with Meezan indicates the petitioner itself did not assert it anticipated the surviving claims.

3. Bottom-line § 102 assessment for the surviving claims

Net conclusion: None of the references I could verify is a clean single-reference § 102 anticipation of the surviving claims 17 and 22; the instituted IPR itself proceeds on obviousness (Gwozdz-PCT in view of Meezan), which is consistent with that assessment. The disclaimed claims 1–16 and 18–21 are no longer enforceable and moot for validity analysis.

4. Residual uncertainty (stated plainly)

• The complete official examiner "References Cited" list for 8,895,546 was not retrievable within my step budget; there may be additional front-page citations (e.g., EP/JP references or additional US art) I could not confirm.
• The exact titles for US 2006/0046962 A1, US 2009/0047347 A1, and the full text of US 6,193,985 B1's title were only partially verified from snippets.
• To close these gaps, pull the front page of the patent from USPTO Patent Center (Appl. No. 13/495,942) or PTAB Exhibit EX1001/EX1004 in IPR2025-00464, which reproduces the granted patent including its citation field.

Primary sources consulted: Google Patents record for US8895546B2 (patents.google.com/patent/US8895546); IPR2025-00464 record and Exhibit 2075 (statutory disclaimer) via Docket Alarm/P-TACTS; family/priority data via Google Patents (WO2012174158/CN103796656A lineage).