US 8329213

I'll search for this specific patent and any associated litigation.

Let me check the litigation references noted on the patent page and any 2026 appellate activity.

Let me verify the actual claim set of US 8,329,213 specifically.

Snapshot — US 8,329,213 B2

Abstract (as published): "The present invention provides liposome compositions containing substituted ammonium and/or polyanion, and optionally with a desired therapeutic or imaging entity. The present invention also provides methods of making the liposome compositions provided by the present invention."

Technical gist

The invention is a remote/transmembrane-gradient loading platform: liposomes whose interior contains a substituted ammonium salt of a polyvalent anion — notably a polyanionized polyol or polyanionized sugar such as sucrose octasulfate (SOS) or inositol hexaphosphate (IHP) — paired with a substituted ammonium (e.g., triethylammonium, TEA). Weakly basic, membrane-permeable drugs (camptothecins such as irinotecan/CPT-11 and topotecan; vinca alkaloids such as vincristine, vinblastine, vinorelbine; anthracyclines such as doxorubicin; ellipticines; and taxane prodrugs) are loaded with near-quantitative efficiency and retained in vivo for long periods. The specification's key reported findings: SOS-based counterions give markedly longer in-vivo drug retention than polymeric anions such as polyphosphate; neutral PEG-lipids (PEG-DSG, PEG-ceramide) permit high loading where anionic PEG-DSPE degrades it; and entrapment reduces rather than increases toxicity relative to free CPT-11.

Independent claims — important caveat on verification

I must flag real uncertainty here. I was able to retrieve the complete claim text for the closely related sibling patent US 8,703,181 (app. 13/654,373, filed Oct. 17, 2012, expressly a continuation of 13/416,204), but not the verbatim claim set of US 8,329,213 itself from a primary source within this session. Do not treat the claim characterizations below as verbatim for '213.

US 8,703,181 (verified, and the closest proxy — same specification, same family, same inventors):

• Claim 1 — A method of delivering an antineoplastic agent to a tumor, comprising administering by injection a composition of an aqueous medium comprising a liposome having an interior space that (1) is aqueous, (2) is separated from the aqueous medium by a lipid membrane, and (3) contains sucrose octasulfate polyanion in the form of a salt of a cationic antineoplastic agent, in an amount sufficient to deliver a therapeutically effective dose to the tumor.
• Claim 11 — A method of delivering irinotecan to a tumor, comprising administering by injection a composition comprising a liposome whose interior aqueous space contains a sucrose octasulfate salt of irinotecan, encapsulated by a lipid membrane.
• Dependent claims add: agent:lipid molar ratio ≥ ~0.05–1.0; neutral or anionic PEG-lipid; fluid parenteral formulation; taxane embodiments; targeting moiety (antibody antigen-binding sequence); and PK/stability limits (irinotecan half-release ≥24 h in mouse, ≥48 h in rat; ≥90% retained after 6 months at 4–8 °C).

For '213 specifically: a third-party litigation analysis of the D.N.J. complaint (see below) characterizes claim 11 of 8,329,213 as a composition claim — "A composition comprising a liposome having an interior space, wherein said interior space: 1) is an interior aqueous space containing a sucrose octasulfate salt of irinotecan, and 2) is encapsulated by a membrane comprising one or more lipids." That is consistent with a division of labor typical of this family (composition claims in one continuation, method-of-treatment claims in another), but I could not confirm it against the granted text. Treat the '213 claim scope as: (a) composition claims directed to a liposome whose interior contains a substituted-ammonium/polyanion (polyol- or sugar-derived) salt, with sucrose octasulfate and irinotecan/CPT-11 as the commercially central species; and (b) possibly method-of-delivery claims.

Litigation posture (as of the data retrieved)

• No Court of Appeals for the Federal Circuit 2026 docket for US 8,329,213 was found. I cannot confirm any CAFC appeal involving this patent; if one exists it did not surface in these searches. Treat "no CAFC 2026 activity identified" as a search result, not a verified negative.
• Active district-court litigation: Ipsen Biopharmaceuticals, Inc. et al. v. Conjupro Biotherapeutics, Inc. et al., D.N.J. 3:24-cv-04991 (Judge Renee Marie Bumb; Mag. J. Matthew J. Skahill), filed April 15, 2024, under 35 U.S.C. § 271 — ANDA case over a proposed generic irinotecan liposome injection (NDA 218923) referencing Onivyde®. Consolidated with 1:24-cv-08723 (order dated Oct. 18, 2024). Patents asserted include 8,329,213 along with 9,339,497; 9,364,473; 9,452,162; 9,492,442; 9,717,724; 10,980,795; 11,369,597; and 12,364,691.
• A global patent-litigation dataset link (Darts-ip, family 35320018) appears on the Google Patents record, indicating first worldwide family litigation.

Sources checked and residual uncertainty

• Google Patents US8329213B2 (authoritative full text supplied): bibliographic data, priority, family, expiration, litigation links.
• Justia Patents / uspto.report: assignee, inventors, filing/issue dates, abstract, examiner, class, and the full claim set for sibling 8,703,181.
• CourtListener / Dockets.Justia / Pacer-derived and DrugPatentWatch records: the D.N.J. 3:24-cv-04991 ANDA action and the patent list.
• Unverified/uncertain: (i) the verbatim independent claim text of '213 itself; (ii) the full asserted-claim list in the D.N.J. action (the complaint reportedly does not chart specific claims); (iii) the absence of any CAFC 2026 appeal. Also note that the automatic assignee field on Google Patents (Ipsen Biopharm Ltd.) and the Justia assignee field (Merrimack Pharmaceuticals, Inc., with PharmaEngine co-listed) reflect different points in time — the recorded chain is Hermes Biosciences → Merrimack → Ipsen Biopharm Ltd. (2017).

I'll research litigation specifically involving US 8,329,213, building on the prior sections rather than repeating them.

Let me search for any other cases asserting '213 — including other ANDA filers and any earlier Merrimack-era suits.

Litigation Report — U.S. Patent No. 8,329,213

Scope note. This section deliberately does not re-do the claim-scope, PTAB, assignment, or prior-art work already presented. It is restricted to the one thing asked: the litigation docket naming 8,329,213 literally. I ran targeted searches on the exact number (not neighbours 8,321,213, 8,329,212, 8,329,214). A search for the bare string "8329213" litigation docket returned zero results, so everything below is drawn from ANDA/Hatch-Waxman litigation repositories, PACER-derived dockets, PTAB filings reproduced in the '552 IPR record, and the Google Patents legal-status block.

1. Answer up front

There is exactly one U.S. court proceeding in which US 8,329,213 has been asserted: the consolidated ONIVYDE® irinotecan-liposome litigation in the District of New Jersey, filed April 15, 2024. That one action has since absorbed two later complaints (different patents, same parties, same product). No other U.S. district court case, and no Court of Appeals for the Federal Circuit appeal, naming '213 was identified in this session. Outside the U.S., the patent's EP counterpart EP 1746976 has been through EPO opposition and appeal — noted at §5 because it is family litigation, not U.S. litigation.

2. The core case — '213 asserted

Current posture (latest docket events retrieved). The case is in fact discovery with contested discovery motions. Docket entries through autumn 2025 include letter motions at ECF 120–124 (taken up at a discovery conference set for December 12, 2025 before Mag. J. Skahill), a joint motion to seal (ECF 125), and pro hac vice admissions (Chetan Chandra for Defendants, 11/21/2025; Yang Wang for Plaintiffs). DrugPatentWatch's case page shows a last-updated stamp of August 3, 2026, which is consistent with a still-live docket but does not itself show any merits outcome. I could not confirm any 2026 trial date or substantive ruling.

2a. Defendant's counterclaims touching '213

Conjupro/CSPC pleaded declaratory judgment counts expressly directed at '213. The counterclaim pleading (reproduced as an exhibit in the '552 IPR file) recites at Count 1 — "Declaratory Judgment of Non-Infringement of the '213 Patent" that "Counterclaim-Defendants have accused Counterclaim-Plaintiffs of infringing claims of the '213 patent in connection with Conjuro's NDA No. 218923," and that Conjupro "do[es] not infringe (either literally or under the doctrine of equivalents), directly or indirectly … any valid, enforceable, properly construed claim of the '213 patent." The pleading also ties jurisdiction to the Paragraph IV Notice Letter, which Ipsen received at the latest by March 7, 2024, and which certified that '213 (among the listed patents) is "invalid, unenforceable, and/or will not be infringed."

2b. Claims charted against '213 in the complaint analysis

The only third-party claim-charting I located identifies independent claim 11 of '213 and its elements as: "A composition comprising a liposome having an interior space, wherein said interior space: 1) is an interior aqueous space containing a sucrose octasulfate salt of irinotecan, and 2) is encapsulated by a membrane comprising one or more lipids." Citations given: '213 col. 2:50-53 and col. 1:24-34. Important caveat, carried forward and still unresolved: this comes from an AI-generated docket analysis, not a scan of the granted patent. The complaint itself, per that same analysis, does not specify which claims are asserted and contains no claim charts — Ipsen pleaded infringement at the product level (Compl. ¶¶ 20, 42, 46). So the asserted claim(s) of '213 remain formally unidentified in the public record; treat "claim 11" as the working hypothesis, not the pleading.

3. Companion actions folded into the same case (no '213 pleaded)

These are relevant to status because they have been consolidated with 24-cv-04991, and the trial/schedule now runs on the consolidated caption.

The later patents were asserted only after they issued and were listed — a pattern of rolling patent-by-patent enforcement against the same NDA, not separate controversies. '213 appears only in the April 2024 complaint.

4. Matters not involving '213 (flagged to prevent misattribution)

• IPR2025-00505 — CSPC Pharmaceutical Group Ltd., CSPC Ouyi Pharmaceutical Co., Ltd. & Conjupro Biotherapeutics, Inc. v. Ipsen Biopharm Ltd., filed Jan. 17, 2025, challenging US 11,344,552 — not '213. Instituted; oral argument scheduled 2026-05-19. RPIs identified: CSPC Group, CSPC Ouyi, Conjupro (Petitioners); Ipsen Biopharm Ltd., plus Ipsen Biopharmaceuticals, Inc. and Ipsen Pharma SAS (Patent Owner). The Board rejected Ipsen's argument that Cipla USA, Inc. was an unnamed RPI.
• IPR2025-01531 — Apotex Inc. v. Ipsen Biopharm Ltd., filed Sept. 12, 2025, also on US 11,344,552. Reported as joined/instituted.
• US 8,321,213 (Jawbone / Sony, IPR2023-01117) — a one-digit transposition of '213 and a wholly unrelated audio patent. Excluded.

The board seat on '213 is empty and it is not an oversight: the very defendants who IPR'd the sibling '552 left '213 to the district court.

5. Non-U.S. family litigation (context, not a U.S. case)

Supplementary protection certificates covering the irinotecan sucrosofate (sucrose octasulfate) salt product exist in Belgium (2017C/027), France, Luxembourg, Ireland, Denmark, and elsewhere — regulatory exclusivity, not litigation, but they are the European analogue of the '213 monopoly and worth knowing about in settlement modelling.

6. ⚠️ Correction to a statement in the earlier litigation/PTAB sections

The earlier section states that "the '213 patent was asserted against Conjupro in the complaint served on or before 2024-03-07 (per Conjupro's own counterclaim pleading, which recites receipt of the notice letter by that date)." That conflates two different events, and the correction matters for § 315(b).

• March 7, 2024 is the date Conjupro/Plaintiffs reference for receipt of the Paragraph IV Notice Letter — which starts the 45-day DJ-jurisdiction clock under 21 U.S.C. § 355(j)(5)(C), not the AIA time bar.
• § 315(b) runs from service of a complaint alleging infringement of the patent. On this docket, waivers of service were sent to all three Defendants on 4/23/2024 and the executed waivers were filed 5/1/2024. The one-year window therefore expired on or about late April / May 2025 — a few months later than the prior section implied, but still long expired. The strategic conclusion (no IPR on '213 because the served defendants are time-barred) is unchanged; only the mechanics and the date shift.

7. Bottom line

1. One U.S. litigation, one case: Ipsen Biopharmaceuticals, Inc. et al. v. Conjupro Biotherapeutics, Inc., CSPC Pharmaceutical Group Limited, and CSPC Ouyi Pharmaceutical Co., Ltd., D.N.J. 1:24-cv-04991 (a.k.a. 3:24-cv-04991), filed April 15, 2024, Judge Bumb/Mag. J. Skahill, §271 ANDA/505(b)(2) action over a proposed irinotecan liposome injection (Conjupro NDA 218923) referencing ONIVYDE®.
2. '213 is asserted there, and is also the subject of Defendant's Count 1 DJ of non-infringement. It remains pending — discovery phase, contested discovery motions, a December 12, 2025 discovery conference, no claim construction order and no merits ruling identified.
3. Two later complaints (24-cv-08723, over the '59,497 patent; 25-cv-13647, over the '69,691 patent) have been consolidated into it; neither pleads '213.
4. No CAFC appeal involving '213 was found. The Board has no proceeding on '213 (IPR2025-00505 and -01531 target the sibling '552). The only appellate-style '213-family event identified is Teva's unsuccessful EPO appeal on EP 1746976.

Residual uncertainty, stated plainly. (i) The asserted claim(s) of '213 in the complaint are not identified in the public record — the "claim 11" identification comes from a third-party AI docket analysis, which also states the complaint contains no claim charts; verify against ECF No. 1 and the Local Patent Rule 3.1 infringement contentions. (ii) I found no § 282 invalidity contention text and no claim construction briefing for '213, so the invalidity theories actually pressed are unknown. (iii) The current docket status as of 2026 could not be confirmed beyond the autumn-2025 entries; PACER (https://pacer.uscourts.gov) or CourtListener docket 68439259 / 68437697 should be checked. (iv) I cannot rule out a second, concurrent ANDA suit by another filer that does not name '213, or a '213 suit not yet in the aggregators — absence of evidence here is a search result, not a verified negative.

Verify at: https://www.courtlistener.com/docket/68439259/ipsen-biopharmaceuticals-inc-v-conjupro-biotherapeutics-inc/ · https://dockets.justia.com/docket/new-jersey/njdce/1:2024cv04991/[546476](/patent/546476) · https://www.drugpatentwatch.com/p/litigation/casename/index.php?query=IPSEN+BIOPHARMACEUTICALS%2C+INC.+v.+CONJUPRO+BIOTHERAPEUTICS%2C+INC.%7C1%3A24-cv-04991 · https://portal.unifiedpatents.com/litigation/New%20Jersey%20District%20Court/case/3%3A24-cv-04991

I'll start by verifying the canonical "no proceedings" result against live sources, and check whether any related-family patents have attracted AIA trials (petitioners sometimes attack siblings instead of the asserted patent).

The first searches returned noise (a homophone patent number, 8,321,213, belonging to Jawbone). Let me run targeted queries on the litigation context and family.

Important finding: there is PTAB activity in this family — but on a different patent (US 11,344,552). Let me confirm whether any AIA trial touches 8,329,213 itself, and check the '552 outcomes for family-level context.

Proceedings overview

Total AIA trial proceedings against US 8,329,213: 0 — no IPR, no PGR, and no CBM, in any status (none active, none instituted, none denied, none settled, none decided on the merits). This matches the canonical USPTO Open Data Portal list supplied in the structured block ("no AIA trial proceedings for this patent"), and my independent searches did not surface any proceeding the ODP had missed.

Bottom line for a defendant: you get neither the windfall nor the headache of a PTAB outcome. There is no Final Written Decision to quote, no canceled claim to point at, and no § 315(e) estoppel tied to this patent. Every claim of '213 — specifically including the composition claim directed to an interior aqueous space containing a sucrose octasulfate salt of irinotecan — remains untested at the Board and fully available to Ipsen in the co-pending D.N.J. action. The real levers on this patent are (a) its clock (adjudicated expiration 2027-01-06 per Google Patents, with a conflicting 2025-05-02 date in an Orange Book extract — see caveats below) and (b) your own § 315(b) time bar, not any Board precedent.

Two family-level proceedings are highly relevant context and are set out below, clearly labeled as NOT against '213.

IPR2025-00505 — CSPC Pharmaceutical Group Ltd., CSPC Ouyi Pharmaceutical Co., Ltd. & Conjupro Biotherapeutics, Inc. v. Ipsen Biopharm Ltd.

• Patent challenged: US 11,344,552 — NOT US 8,329,213.
• Type: Inter Partes Review
• Filed: 2025-01-17
• Status: Instituted for trial. Per a practitioner docket tracker (paragraphfour.com, accessed 2026-09-28), oral argument was scheduled for 2026-05-19. I could not confirm from a primary source whether a Final Written Decision has issued, nor its outcome. Do not assume a result.
• Judge panel: Not confirmed in the material I retrieved. Note that under the institutional changes effective October 2025, the Director (not the merits panel) makes the institution call for petitions not already referred to a panel before 2025-10-20; whether this petition was referred pre-change is not established here.
• Petition grounds: Obviousness, § 103. Challenged claims 1–15. Ground 1: claims 1, 3–6, 8–14 obvious over Conroy, Conroy Protocol, Conroy Appendix, and Mahaseth in view of Bayever, Saif, Ko, and Cantore (the FOLFIRINOX / liposomal-irinotecan substitution theory). Ground 2: claims 2, 7, 15 over the Ground 1 art plus Masi and Ginocchi (administration sequence).
• Institution decision: Instituted (Board decision granting institution is Paper 13, referenced in the patent owner's expert declaration). Petitioner's opposition to Ipsen's request for discretionary denial briefed §§ 314(a) Fintiv and 325(d)/Becton Dickinson issues; those arguments were evidently rejected at institution.
• Final Written Decision: Not confirmed. Statutory deadline under § 316(a)(11) is one year from institution; if the Board instituted in mid-2025, an FWD would be due around mid-2026. I am not reporting a verdict I could not verify.
• Settlement / termination: None identified.
• Appeal: None identified.
• Defensive value: Only indirect. A loss on '552 would not cancel any '213 claim, but it would show that the Conroy/Bayever FOLFIRINOX art (which the '552 petitioner relied on) has force in this family — and that art is not § 315(e)(2)-estopped against '213, since it was raised in a different proceeding.

IPR2025-01531 — Apotex Inc. v. Ipsen Biopharm Ltd.

• Patent challenged: US 11,344,552 — NOT US 8,329,213.
• Type: Inter Partes Review
• Filed: 2025-09-12
• Status: Reportedly joined to IPR2025-00505 and instituted for trial.
• Everything else (panel, grounds, FWD, appeal): not confirmed in the sources retrieved. Single-source item — this proceeding number appears only in the paragraphfour.com docket activity page; treat the join and institution as reported, not verified.
• Defensive value: Confirms a second, independent generic challenger (Apotex) chose to attack the '552 method patent, not the '213 composition patent. That is a signal about where challengers think the family's vulnerability sits — and it is not '213.

⚠️ Number-confusion trap: US 8,321,213 ≠ US 8,329,213

Web searches for "'213 IPR" prominently surface IPR2023-01117, Sony Electronics Inc. v. Jawbone Innovations, LLC, U.S. Patent No. 8,321,213 (adaptive-null-direction hearing instrument — Avendano/Visser art). That is a one-digit transposition and a completely unrelated patent (audio, not liposomes). Do not pull that FWD into a validity opinion for this patent. This is exactly the kind of "candidate invalidating reference" that ends up in a brief by mistake.

Strategic summary

Claim status. Because there is no PTAB proceeding on '213, no claim of '213 is canceled and no claim has been sustained in an FWD. The entire claim set is legally untested before the Board. Consistent with the caveat in the earlier section of this analysis, the '213 claim set itself was not retrievable verbatim in this session; the D.N.J. complaint analysis characterizes independent claim 11 as a composition claim to "an interior aqueous space containing a sucrose octasulfate salt of irinotecan… encapsulated by a membrane comprising one or more lipids." Treat that as a third-party (AI-derived docket summary) characterization, not a verified quotation. All claims should be assumed live and untested for defensive planning purposes.

Estoppel landscape. Clean. § 315(e)(2) estoppel is patent- and claim-specific; it runs from an FWD in IPR2025-00505/01531 to the '552 patent only. Nothing estops any ground against '213, and the '505 petitioner's FOLFIRINOX art remains fully available in the district court and, for an unserved party, at the Board. Conversely, § 315(b) is your binding constraint: the '213 patent was asserted against Conjupro in the complaint served on or before 2024-03-07 (per Conjupro's own counterclaim pleading, which recites receipt of the notice letter by that date; suit filed 2024-04-15). One year from service has long since run — that time bar almost certainly explains the absence of an IPR on '213 from the very defendants who are IPR-ing the sibling '552. A defendant served with a '213 complaint in 2024 is now locked into the district-court invalidity case; a newly served party (for example, a different ANDA filer) would still have its one-year § 315(b) window.

Pattern signals. (1) No serial petitions on this patent — it has drawn zero. (2) No defensive aggregator: the Unified Patents link on the Google Patents record is a litigation-data link to the D.N.J. case, not a Unified Patents validity challenge; Unified is not a party. (3) Same challenger group, different target: Conjupro/CSPC is attacking '552 and pleaded invalidity counterclaims on '213, '497, '473, '162, '442, '724, '795, '597, '867, '360, and '914 in district court — deliberately, or by time bar, keeping the Board out of '213. (4) The Board is now a harder forum than it was: FY2025 saw record procedural denials and institution rates under 15–38%, Director Squires assumed institution authority for IPR/PGR on 2025-10-16, and the October 2025 proposed rules would bar institution where a parallel proceeding will decide validity first or where a claim has previously survived a validity challenge. A 2004-priority, 2012-issued patent like '213 is squarely within the "settled expectations" denial cohort the PTO has invoked to deny hundreds of petitions since 2025. Any IPR strategy against '213 must be stress-tested against that regime, not the 2015–2024 playbook.

Recommended next steps

1. State it plainly, and say why it matters. There is no PTAB activity on US 8,329,213 — none. The absence is a signal, not a blank: this is a patent asserted in an ANDA case since April 2024 that has nonetheless never been petitioned at the Board, most plausibly because the served defendants are § 315(b) time-barred on it. If you are a newly served defendant, check your service date before anything else — the § 315(b) window is the whole game on this patent.
2. Don't litigate a patent that may be near its end without pricing the term. Google Patents reports the adjusted expiration as 2027-01-06 (consistent with paragraphfour.com's listing of 8,329,213 at 1/6/2027). But an Orange Book extract (drugfuture.com, NDA 207793) lists 8329213 with expiration 2025-05-02, and paragraphfour.com separately lists the sibling patents 8,703,181 / 8,992,970 / 9,724,303 / 8,730,891 / 9,782,349 / 10,722,508 as expiring 5/2/2025. Resolve this divergence against the current FDA Orange Book listing and the PTA/terminal-disclaimer record before relying on either date — a patent whose effective life is measured in months (or zero) is a very different settlement posture.
3. Monitor IPR2025-00505 for the FWD. Verify at PTAB E2E (https://ptacts.uspto.gov) whether a Final Written Decision has issued and what it held on claims 1–15 of '552 — I could not confirm the outcome. If the Board invalidated '552 claims on Conroy/Bayever, that art becomes the strongest non-estopped 102/103 theme for '213; if it sustained them, adjust expectations for the whole family.
4. Treat the district court as the real arena. The live fight is Ipsen Biopharmaceuticals, Inc. et al. v. Conjupro Biotherapeutics, Inc. et al., D.N.J. 3:24-cv-04991 (consolidated with 1:24-cv-08723; a third Ipsen case, 1:25-cv-13647, over the '691 patent), where Conjupro has already pleaded declaratory-judgment counts of non-infringement and invalidity as to '213 (Counterclaim Count 1). CourtListener: https://www.courtlistener.com — docket 3:24-cv-04991.
5. Do not import the wrong FWD. If research is delegated, flag US 8,321,213 / IPR2023-01117 (Jawbone) as a lookalike number with no relation to this patent.

Residual uncertainty (stated honestly). (i) I could not retrieve a verbatim, complete claim set of US 8,329,213 in this session, so the identifications of challenged/asserted claims above are limited to what the sources quoted; (ii) the outcome of IPR2025-00505 is unverified, including whether an FWD has issued; (iii) IPR2025-01531 rests on a single secondary source; (iv) the '213 expiration date is reported inconsistently across sources and my 2026-09-28 check of the Orange Book extract conflicts with Google Patents. None of these uncertainties changes the headline: zero AIA trial proceedings on US 8,329,213.

I'll reconstruct the assignment record from USPTO Assignment Center and cross-reference. Let me run several targeted searches.

Let me try to locate the specific recorded assignments and correspondents.

Assignment Record Reconstruction — US 8,329,213 B2

Source limitation, stated up front: my only retrieval tool in this session is general web search. USPTO Assignment Center (https://assignmentcenter.uspto.gov/) is not directly queryable from here, and no search I ran returned reel/frame numbers or correspondent-of-record data for this patent. Every event below is reconstructed from the Google Patents "Legal Events" (reassignment) block for US8329213B2, which is populated from USPTO assignment data — but I could not retrieve the reel/frame pairs or the recording correspondent for any entry. I am flagging that gap rather than inventing numbers. Verify each event at https://assignment.uspto.gov/patent/index.html#/patent/search by entering patent number 8329213.

Inventors

Basis for the employer call: the record contains an Assignment of Assignors' Interest conveying rights from these three inventors to Hermes Biosciences, Inc. (recorded 2014-08-27). The obligation to assign ran to Hermes, which is the classic signature of employee inventors.

Unusual patterns — assessment:

• No "inventors departed within 12 months of filing" signal. Application 13/416,204 was filed 2012-03-09, but it is a continuation of 11/121,294, which traces to the 2004-05-03 priority. The economically meaningful filing date for inventorship purposes is ~2004–2005, not 2012. Whether the inventors left Hermes shortly after the original 2005 filing is not determinable from the data retrieved.
• What is unusual is the 2014 confirmatory assignment from the three inventors to Hermes Biosciences — recorded two years after issuance and roughly five years after Merrimack had already absorbed Hermes by merger. That is a latent chain-of-title defect being papered over, not a live transfer. It is a real diligence flag: an assignee recording inventor assignments after granting and after a merger is cleaning up a gap, and the cleanup was triggered by something (likely the 2014 Baxalta/Shire out-license diligence rather than litigation).
• Both Drummond and Kirpotin are long-tenured Merrimack-side liposome scientists post-acquisition; I could not verify their individual departure dates from any primary source in this session.

Original assignee

Merrimack Pharmaceuticals, Inc. (Cambridge, MA; Delaware corp.; SEC CIK 0001274792; NASDAQ: MACK).

• Line of business: clinical-stage oncology company (nanotherapeutic/liposomal drug delivery and antibody therapeutics).
• How it acquired the patent: not by assignment from Hermes directly, but by the 2009 acquisition of Hermes Biosciences, Inc., effected through the Merger / Certificate of Ownership and Merger recorded 2012-04-19 ("MERIMACK PHARMACEUTICALS, INC. … CERTIFICATE OF OWNERSHIP AND MERGER, Assignors: HERMES BIOSCIENCES, INC."). Press/secondary sourcing dates the Hermes acquisition to December 2009 (San Francisco Business Times, Dec. 8, 2009).
• Did it ship a product embodying the claims? Yes. Merrimack developed and, on 2015-10-22, obtained FDA approval of ONIVYDE® (irinotecan liposome injection), NDA 207793 — the commercial embodiment of the '213 family (irinotecan remote-loaded into liposomes via a sucrose-octasulfate/triethylammonium gradient, per the specification's Examples 9/14/15 and Figs. 1–7).
• Current status: Operating, but no longer the owner of this patent. Merrimack sold its ONIVYDE/MM-436 commercial business to Ipsen under an Asset Purchase and Sale Agreement dated 2017-01-07, closing 2017-04-03, for $575M cash plus up to $450M in FDA-approval milestones. Post-sale Merrimack retained MM-121, MM-141 and MM-310 (~80 employees). I retrieved Merrimack filings through FY2017 only; I cannot confirm from this session whether Merrimack remains an active registrant, has wound down, or has been acquired. Treat "operating" as accurate as of 2017 and unverified thereafter.

Assignment timeline

Reel/frame and correspondent fields: NOT RETRIEVED. Listed as [not retrieved] for every entry. Dates are execution/recording dates as reported in the Google Patents legal-events block; where execution and recording dates likely differ I say so.

2012-04-19 — recorded 2012-04-19 — Reel [not retrieved]

• Conveyance: Certificate of Ownership and Merger
• Assignor: Hermes Biosciences, Inc.
• Assignee: Merrimack Pharmaceuticals, Inc.
• Correspondent: [not retrieved] — could not be captured. Because this is a merger certificate rather than a negotiated assignment, the filing correspondent is likely Merrimack's corporate/outside IP counsel; unverified.
• Context: Internal corporate reorganization — recordation of Merrimack's 2009 acquisition of Hermes by merger; this is the root of Merrimack's title.

2014-08-27 — recorded 2014-08-27 — Reel [not retrieved]

• Conveyance: Assignment of Assignors' Interest
• Assignor: Drummond, Daryl C.; Hong, Keelung; Kirpotin, Dmitri (individual inventors)
• Assignee: Hermes Biosciences, Inc.
• Correspondent: [not retrieved] — flag: the recording attorney here is the single most valuable remaining lead in this chain. An inventor-to-company assignment recorded in 2014 for a 2004-priority family was drafted by whichever firm was then doing Merrimack's IP diligence; capturing that name lets you check it against the other family members (8,703,181; 8,992,970; 9,717,724; etc.) for recurrence. Unretrieved.
• Context: Confirmatory/chain-of-title cleanup, not a new transfer — Hermes had already ceased to exist as a separate owner by merger; this was recorded to cure a missing inventor assignment behind the merger chain.

2015-12-28 — recorded on or about 2015-12-28 — Reel [not retrieved]

• Conveyance: Security Interest (see document for details)
• Assignor: Merrimack Pharmaceuticals, Inc.
• Assignee: U.S. Bank National Association, as Collateral Agent
• Correspondent: [not retrieved].
• Context: Securitization / collateral pledge — a floating lien over Merrimack's IP securing a debt facility, not a transfer of ownership. Corroborated by Merrimack's 2016 10-K describing a Loan and Security Agreement dated 2016-11-08 with BioPharma Credit Investments I (and the later 10-K reference to an indenture discharged 2017-04-03).

2017-04-14 — recorded 2017-04-14 — Reel [not retrieved]

• Conveyance: Release by Secured Party
• Assignor: U.S. Bank National Association (as Collateral Agent)
• Assignee: Merrimack Pharmaceuticals, Inc.
• Correspondent: [not retrieved].
• Context: Discharge of the 2015 security interest — matches the 10-Q statement that "the indenture was satisfied and discharged on April 3, 2017." Necessary clean-up so that the subsequent asset sale could convey unencumbered title.

2017-05-01 — recorded 2017-05-01 — Reel [not retrieved]

• Conveyance: Assignment of Assignors' Interest
• Assignor: Merrimack Pharmaceuticals, Inc.
• Assignee: Ipsen Biopharm Ltd. (Ash Road, Wrexham Industrial Estate, Wrexham, GB LL13 9UF, United Kingdom)
• Correspondent: [not retrieved]. Flag: the July 2017 "Change of Address of Assignee" entry for an Ipsen UK entity (Wrexham address) was almost certainly filed by the same correspondent as this May 2017 assignment; capturing that firm gives you the recurring recorder for the entire ONIVYDE patent family transfer, which spans dozens of US and foreign family members.
• Context: Asset sale closing. Merrimack's ONIVYDE/MM-436 commercial business IP was sold to Ipsen (agreement 2017-01-07; close 2017-04-03; respective executors signed and recorded through May 2017). This is the single substantive third-party transfer in the patent's history.

2017-05-17 — recorded 2017-05-17 — Reel [not retrieved]

• Conveyance: Change of Address of Assignee
• Assignor: Merrimack Pharmaceuticals, Inc. (as listed)
• Assignee: Ipsen Biopharm Ltd.
• Correspondent: [not retrieved].
• Context: Change of address only — no change in ownership. Administrative; do not count this as a transfer link in the chain.

Net count of ownership-conveying events: one merger (2012), one confirmatory inventor assignment (2014), one security interest + release (2015/2017), one sale to Ipsen (2017), one address change (2017). No post-2017 ownership events appear in the record.

Timeline diagram

timeline
    title Ownership of US 8329213
    2004 : Priority date May 3
    2005 : Parent application filed
    2009 : Merrimack acquires Hermes Biosciences
    2012 : Merger certificate recorded
         : Patent issues Dec 11
    2014 : Confirmatory assignment from inventors
    2015 : Security interest to US Bank
         : Onivyde approved Oct 22
    2017 : Security interest released
         : Asset sale to Ipsen Biopharm
    2024 : Ipsen sues Conjuro over Onivyde

NPE / troll-pattern signals

1. Shell-entity transfer — NOT PRESENT. Every assignee in the chain is an operating entity: Hermes Biosciences, Inc. (drug-delivery R&D), Merrimack Pharmaceuticals, Inc. (public oncology company, SEC CIK 1274792, NASDAQ: MACK), U.S. Bank N.A. (collateral agent for a debt facility), and Ipsen Biopharm Ltd. (UK manufacturing/sales subsidiary of Ipsen S.A.). No "IP / Holdings / Ventures" suffix, no Delaware/Texas single-purpose LLC, no registered-agent service address. The Wrexham address on the Ipsen entity is a real industrial-estate manufacturing site used in HK IP Journal listing 18 Oct 2019, not a mail-drop.

2. Known asserter in the chain — NOT PRESENT. Neither current assignee (Ipsen Biopharm Ltd.) nor any prior assignee matches Acacia, Marathon, IV, IPNav, Wi-LAN, Conversant/Mosaid, Vringo, Pendrell, Innovatio, MPHJ, Lumen View, Round Rock, Spangenberg entities, or any Unified Patents / RPX high-frequency-plaintiff listing. Ipsen is a €1.6B-revenue specialty pharma group with over 20 marketed drugs — the archetype of an operating-company plaintiff, not an asserter.

3. Repeat correspondent across the chain — UNCLEAR / NOT RETRIEVED. The correspondent field could not be captured for any of the six recorded events. This is the one signal I cannot score, and it is the signal the task specifically asks me to be precise about. A single appearance would not be a finding anyway — Merrimack/Ipsen use large general-practice IP firms. The test would be whether the same firm recorded the 2012 merger certificate, the 2014 inventor cleanup, and the 2017 sale; if so, that reflects continuity of corporate counsel, not an NPE recording mill.

4. Cascading transfers — NOT PRESENT. Six recorded events across 2012–2017, of which only one (2017-05-01) conveys beneficial ownership to a third party. No chained LLCs, no transfers in under 24 months through successive shells, no shared correspondent addresses.

5. Pre-litigation transfer — NOT PRESENT. The operative transfer (to Ipsen) is dated 2017 — roughly seven years before the first infringement suit naming this patent (Ipsen Biopharmaceuticals, Inc. et al. v. Conjuro Biotherapeutics, Inc. et al., D.N.J. 3:24-cv-04991, filed 2024-04-15, triggered by Conjuro's March 2024 Paragraph IV notice). The assignment was made in connection with a $575M product-asset purchase, not to enable assertion — the lawsuit followed the product, not the paper.

6. Bankruptcy fire-sale — NOT PRESENT. Merrimack's 2017 disposition of this IP was a board-approved, stockholder-ratified asset sale under an Asset Purchase and Sale Agreement (8-K, 2017-01-09), with a $575M cash price plus $450M contingent milestones. I found no Chapter 7/11 filing by Merrimack or Hermes in the retrieved materials. The 2015–2017 U.S. Bank / BioPharma Credit secured-debt activity is ordinary venture-debt collateralization, not insolvency.

7. Privateering — NOT PRESENT. Ipsen acquired the patents together with the product, the NDA, the manufacturing facility sublease, employees, and the Shire and PharmaEngine licenses. Ipsen markets ONIVYDE itself and asserts these patents against a direct generic competitor. This is a vertical product acquisition and a normal Hatch-Waxman §271(e)(2) assertion, not a proxy campaign.

8. Defensive aggregator — NOT PRESENT. The chain terminates at Ipsen Biopharm Ltd., an asserting operating company. No RPX/AST/LOT/Unified/OIN terminus.

Verdict

Operating-company assertion.

The chain is Hermes Biosciences → Merrimack Pharmaceuticals, Inc. (merger certificate recorded 2012-04-19; confirmatory inventor assignment recorded 2014-08-27) → Ipsen Biopharm Ltd. (assignment recorded 2017-05-01), with a 2015-12-28 security interest to U.S. Bank N.A. and its 2017-04-14 release being pure financing events that never conveyed beneficial ownership. The current assignee is a subsidiary of a publicly traded specialty pharma that manufactures and sells the patented product — ONIVYDE (irinotecan liposome injection, NDA 207793, approved 2015-10-22) — and is asserting the patent in a run-of-the-mill ANDA case against a would-be generic entrant, with the operative transfer occurring seven years before the suit rather than six months. Not one of the eight NPE signals scores "present"; the only two I could not score (repeat correspondent, and confirmatory-assignment motive) suffer from a data gap, not from adverse evidence.

Two residual uncertainties I will not paper over: (i) all reel/frame numbers and correspondents are unretrieved — the entries above are dated from Google Patents legal events and should be confirmed line-by-line at Assignment Center before being used in a diligence memo; (ii) Merrimack's post-2017 corporate status is unverified in this session.

Verify at: https://assignment.uspto.gov/patent/index.html#/patent/search (patent number 8329213) and https://assignmentcenter.uspto.gov/.

Cross-check against prior sections — one contradiction to flag

The previously generated snapshot lists the current assignee as Ipsen Biopharm Ltd. while noting Justia lists Merrimack Pharmaceuticals, Inc. with PharmaEngine co-listed. The assignment record resolves this in favor of Ipsen Biopharm Ltd.: the 2017-05-01 Assignment of Assignors' Interest from Merrimack to Ipsen is the last ownership-conveying event, followed only by a 2017-05-17 Change of Address of Assignee. The Justia "Merrimack / PharmaEngine" field is a snapshot of the inventor-side prosecution record (Hermes had a 2005 license/assignment arrangement with PharmaEngine, per Merrimack's SEC exhibits), not of current title. Also note the 2024 D.N.J. plaintiff is Ipsen Biopharmaceuticals, Inc. (the US affiliate, Basking Ridge NJ) suing alongside/under Ipsen Biopharm Ltd. as owner — consistent with, not contrary to, the recorded chain.

I'll research US 8,329,213 and its cited prior art directly.

Let me try to retrieve the actual "Patent Citations" table for US 8,329,213 and verify its claims.

Prior-Art Analysis — US 8,329,213 B2

Exact-ID search result. Searching specifically for the number 8329213 returns US 8,329,213 B2, "Liposomes useful for drug delivery," application 13/416,204, filed 2012‑03‑09, granted 2012‑12‑11, inventors Keelung Hong, Daryl C. Drummond, Dmitri Kirpotin — and only that patent. I did not pick up any confounding entries for neighboring numbers (e.g., 8,329,212 / 8,329,214 / 8,329,213‑family publications are distinct and are labelled as such below). Source records: Google Patents US8329213B2 (https://patents.google.com/patent/US8329213B2/en), USPTO PatentCenter/Assignment links on that record, and the Orange Book listing for NDA 207793 (Onivyde) via drugfuture.

⚠️ Three things I must flag before the substance

1. I could not retrieve the face-of-patent citation list for '213 itself. The "References Cited" / "Patent Citations" and "Cited By" tables on the '213 record did not render through my available search tooling, and I hit a tool-step cap before completing direct pulls from USPTO PatentCenter / Justia for '213. Accordingly, the enumeration below is not a verified transcription of the examiner-cited references on the '213 front page. Where a reference is included, I label its provenance. I will not invent a citation list.

• To close this gap in one step, pull the "References Cited" section from (a) the printed first page of the granted patent PDF, (b) PatentCenter → Application Data → "References Cited," or (c) the Google Patents "Patent Citations" accordion on US8329213B2.

2. Contradiction on term/expiry — flagged, not reconciled.

• Google Patents (authoritative text supplied): Adjusted expiration 2027‑01‑06; "Active."
• Orange Book listing surfaced via drugfuture (NDA 207793): US 8,329,213 expires 2025‑05‑02 (same date given for 8,703,181 and 8,992,970), with 8,147,867 at 2028‑08‑29.
• A separate aggregator (pharsight.greyb) shows Onivyde family patent expiry in May 2025. These are not consistent with the 2027‑01‑06 adjusted date and typically reflect different things (Orange Book listed expiry vs. PTA-adjusted expiry vs. terminal disclaimer). Treat the discrepancy as unresolved.

3. Priority date governs the §102 analysis. '213 is a pre‑AIA continuation (app. 13/416,204, filed before 2013‑03‑16) claiming the May 3, 2004 provisional priority. So the operative dates are §102(a)/(e): before 2004‑05‑03, and §102(b) statutory bar: before 2003‑05‑03. Anything published 2004–2012 (Hattori 2009 on phytic‑acid irinotecan liposomes; Drummond 2006; Noble 2006; Messerer 2004; Dickinson 2008; Krauze 2007) is not §102 prior art against '213 and cannot anticipate it — it is at most background. This is an important correction to the way those references are often lumped into "prior art" discussions of the Onivyde family.

A. References appearing inside the '213 specification itself (verified — this text is authoritative)

These are the references the inventors themselves relied on to frame the invention. They are the most defensible "cited material" I can hand you, and several are express incorporations by reference.

B. Candidate citations not verified as being on the '213 face (provenance labelled)

B‑1. From the prosecution of the sibling Merrimack case US 8,658,203 ("Liposomes useful for drug delivery to the brain," app. 11/601,451, filed 2006‑11‑17 — same inventors Drummond and Kirpotin, same family technology; Justia record: https://patents.justia.com/patent/[8658203](/patent/8658203)). Its citation list includes: Sadzuka et al., Cancer Lett. 127(1‑2):99‑106 (1998); Chou et al., J. Biosci. Bioeng. 95(4) (2003), "Effect of composition on the stability of liposomal irinotecan prepared by a pH gradient method"; Ochi 1980; Hattori et al., J. Control. Release 136:30‑37 (2009); Messerer et al. (2004); Noble et al. (2006); Drummond et al. (2006); Dickinson et al. (2008); Krauze et al. (2007).

• Of these, only Chou 2003 (pH‑gradient liposomal irinotecan) and Sadzuka 1998 (liposomalization of CPT‑11) predate 2004‑05‑03 and are live §102(b)/§103 references, and only against generic "liposomal irinotecan" concepts — neither discloses a sucrose-octasulfate/irinotecan salt inside the liposome.
• Hattori 2009 (phytic‑acid irinotecan liposome) is the closest conceptual neighbour to the SOS platform, but it postdates the '213 priority by five years and therefore cannot be §102 prior art against '213. It is prior art only against later family members.

B‑2. References surfaced from the ISR of PCT/EP2009/062543 (WO2010034837A1) — these are the classic remote-loading citations in this field, but I have not confirmed they appear on the '213 front page: US 5,814,335 A (Webb et al., 1998‑09‑29); US 6,083,530 A (Mayer et al., 2000‑07‑04); US 5,082,664 A (Lenk et al., 1992‑01‑21); WO 98/18450 (Univ. British Columbia, Fenske/Cullis, 1998‑05‑07); EP 0 290 296 A (Liposome Co., 1988‑11‑09); US 4,619,794 A (Hauser, 1986‑10‑28); WO 96/32930 (Yissum/Dehlinger, 1996‑10‑24); WO 98/33484 (Univ. California, 1998‑08‑06).

All eight predate 2004‑05‑03 and are therefore usable §102(b) art — but they are only "of record" here if they also appear on '213. Verify before relying on them.

B‑3. ZoneOne Pharma US 10,004,759 cites US 8,329,213 (i.e., '213 is cited by later art, not as prior art to it). That record lists WO 1990/011780, WO 2000/009089, WO 2007/026028, WO 2011/092708, WO 2012/118376, WO 2014/121211, WO 2014/121235, WO 2014/153192, WO 2016/022549, WO 2016/025559, WO 2016/025611 and EP 2415470. All are 2007 or later — none is prior art against '213.

C. Which claims a reference could anticipate under §102 — provisional mapping

Claim-scope caveat (carried forward and still unresolved): the verbatim claim set of '213 was not retrievable this session. The working characterisation is: (i) claim 1 = composition — a liposome in a medium whose interior contains a substituted ammonium of the Markush formula [1*]N+([3*])[4*] with R¹–R⁴ limits (≥1 organic group; ≤8 C each, ≤18 C total; ≥3 organic groups or a sterically hindered ammonium) and the pKa ≥ ~8.0 feature; (ii) a polyanion embodiment claim — interior polyanion that is a polyanionized polyol or polyanionized sugar; (iii) claim 11 = composition, per third-party characterisation of the D.N.J. complaint, of a liposome whose interior aqueous space contains a sucrose octasulfate salt of irinotecan encapsulated by a lipid membrane.

Bottom line on §102: on what I could verify, no reference I can identify discloses the interior sucrose-octasulfate salt of irinotecan inside a lipid-membrane liposome, or a substituted ammonium (TEA/DEA) polyanionized-sugar salt in a liposome interior, before 2004‑05‑03. Anticipation risk against claim 11 is therefore low on the verified record; the real exposure is §103 over the Haran/Maurer-Spurej/Bally‑lineage gradient-loading art combined with the SOS/Ochi salt chemistry, plus §112-type issues on the Markush breadth. The examiner's actual §102 rejections, if any, would have to be read off the file wrapper (see next step).

D. Recommended next actions (to convert the above from provisional to verified)

1. Pull the front-page "References Cited" for US 8,329,213 from PatentCenter (Application 13/416,204) or the granted PDF — this is the single missing input.
2. Pull the claim set verbatim (PatentCenter → Claims; the earlier snapshot's "claim 11 composition" characterisation came from a third-party litigation analysis, not the granted text).
3. Pull the Image File Wrapper for 13/416,204 and the parent 11/121,294 (US 8,147,867) to see which of A1–A5, B‑1 and B‑2 the examiner actually applied, and under which subsection.
4. If authenticating against US 5,192,549 / US 5,316,771 / US 5,077,056 (Bally et al., Liposome Company) — the classic Bally-lineage active-loading patents that sit directly under the '213 gradient-loading concept — I flag that I did not verify these numbers or their contents this session; confirm number, assignee, claims and loading protocol before treating them as §102(b) references.

Residual uncertainty, stated plainly: (i) the verbatim citation list on '213 is unverified; (ii) the verbatim claim set of '213 is unverified; (iii) exact publication dates for US 5,783,568, US 5,281,237 and WO 96/25147 are given from number-series inference at moderate confidence, not from a primary bibliographic record; (iv) the 2025‑05‑02 vs. 2027‑01‑06 expiry conflict is not reconciled; (v) no CAFC 2026 docket for '213 was found, but that is a search result, not a verified negative.

I'll ground this analysis in the actual prior-art record for this patent. The supplied Google Patents text did not include a discrete "Prior Art" citation section, so let me retrieve the cited references and the key field art directly.

Good grounding. Let me pull the actual prior-art citation record for this family and the closest Inex/Bally polyanion-trapping art.

Obviousness Analysis — U.S. Patent No. 8,329,213 under 35 U.S.C. § 103

0. Preliminary scope notes (important, and I flag them rather than paper over them)

1. The supplied Google Patents text contains no discrete "Prior Art" citation section. The fetched record reproduces the bibliographic data and the description, but the "Citations / Cited By" tables did not come through in the supplied text. I therefore reconstructed the prior-art record from (a) references cited inside the authoritative specification text you supplied, and (b) the family's PCT/EP prior-art and prosecution record (WO2005107712 / EP1746976). I flag this as a limitation on completeness.
2. Claim language is a proxy. Consistent with my earlier flag: I have not verified the verbatim granted claim set of '213 itself. For the analysis below I use (i) the claim text I retrieved from the closest family member, AU 2005240131 C1 ("Liposomes useful for drug delivery," same priority 2004-05-03, same inventors), whose claims 1, 19, 20 and 51 track the composition/method structure; and (ii) the litigation-derived characterization of '213 claim 11 as a composition claim reciting an interior aqueous space containing "a sucrose octasulfate salt of irinotecan." Treat the claim framing as provisional and confirm against the granted text.
3. Critical date. Earliest priority is May 3, 2004 (provisional 60/567,921). The '213 application (13/416,204) is a continuation; pre-AIA §§ 102/103 apply, with a 2004 critical date. This matters a great deal: several references that look on-point (Zhigaltsev 2005/2006; Ramsay 2006; Taggar 2006; Drummond, Cancer Res. 66:3271, 2006) are at or after the critical date and are therefore not § 102(b) prior art — I exclude them from the affirmative case and use them only to describe the field's trajectory.

1. The prior-art landscape

2. Ground-by-ground § 103 analysis

Ground 1 (primary): Madden '008 + Haran (+ Maurer-Spurej)

The combination supplies every element of the composition genus, and the motivation is strong:

• Liposome with an interior polyanionic trapping agent → Madden '008 (dextran sulfate; sulfated polysaccharides; chondroitin sulfates; "other polymers are suitable including sulfated … hydrophilic polymers").
• Remote loading of a camptothecin (irinotecan/topotecan) → Madden '008, and Tardi 2000.
• Ammonium transmembrane gradient + counterion-controlled retention → Haran 1993 and Maurer-Spurej 1999.
• A mono/disaccharide polyanionized with ≥2 strongly anionic groups, e.g., sulfated sucrose → supplied by a single substituent swap of a known polyanion from Madden's express list, using SOS, whose identity, salt forms, and strong-acid behavior were long known.

Motivation to combine (KSR / Graham):

1. Same field, same problem, same mechanism. Both Madden '008 and Haran address the identical problem — retaining a basic drug in a liposome to improve PK and reduce toxicity — and both use an impermeant counter-anion/ammonium gradient.
2. Haran teaches the operative variable. Haran states outright that retention "is related to the low permeability of its counterion … which also stabilizes anthracycline accumulation … due to the aggregation and gelation of [the] sulfate salt." That is an express teaching to select the counter-anion by impermeability and salt-gelling capacity — the very properties SOS maximizes (eight sulfates, pKa ≈ 1). A POSITA optimizing retention would predictably increase anion valency/charge density.
3. Madden invites the substitution. Its trapping-agent disclosure is a genus ("polyanionic polymer") with an open-ended list and the express statement that "other polymers are suitable." Under KSR, a finite set of identified, predictable solutions with a reasonable expectation of success is obvious to try (In re Wands factors (A)–(B)).
4. The sugar limitation points toward, not away from, SOS. Dextran sulfate and chondroitin sulfate — Madden's own examples — are themselves sulfated polysaccharides. A sulfated disaccharide (SOS) is the obvious lower homolog/oligomer of that exact class. The claim's monosaccharide/disaccharide limitation thus narrows into a region Madden already sails toward.

Ground 2: Madden '008 + US 5,281,237 & US 5,783,568 ("polyanionized sugar/polyol" genus)

The '213 specification itself cites US 5,281,237 and US 5,783,568 as disclosing "sulfated, sulfonated, and phosphorylated sugars and polyols." A patentee's own acknowledgment that a genus of anionic sugars/polyols was known is a classic § 103 admission. Combined with Madden's teaching to place a polyanionic trapping agent inside a liposome, the genus claim ("polyanionized sugar or polyol") is a straightforward substitution of one known polyanion class for another with predictable results. This Ground is strongest against the genus claim and weakest against the SOS species.

Ground 3: Substituted-ammonium (e.g., triethylammonium) limitations

The '213 spec admits that "titratable ammonium such as unsubstituted ammonium ion (NH₄⁺)" and "primary and secondary straight chain alkylammonium ions in the inner space of the liposome … [are] known to provide for enhanced encapsulation … via … 'active', 'remote', or 'transmembrane gradient-driven' loading." Haran supplies NH₄⁺; Madden '008 supplies the substituted-ammonium/dextran-sulfate pairing ("dextran ammonium sulfate"); and a co-pending commonly owned Hermes-family publication (US 2005/0112065 A1) discloses a marker trapped "in the form of an ammonium or substituted ammonium, e.g., triethylammonium, salt." The pKa ≥ 8.0 limitation is routine optimization — the spec concedes that pKa values for amines "are tabulated in reference books of chemistry and pharmacology." Caveat: because US 2005/0112065 appears commonly owned with '213, pre-AIA § 103(c) may disqualify it as prior art for obviousness; I flag it as a lead, not a cornerstone.

Ground 4: Method-of-encapsulation claims (cf. AU '131 claim 51)

Mayer 1986, Madden 1990, Haran 1993, and the Bally ion-gradient/ionophore patents collectively teach the recited steps — create a transmembrane ammonium/substituted-ammonium gradient, contact the liposome with a membrane-permeable basic entity, let the entity partition and be trapped as a liposome-internal salt. The method claims are conventional application of the art.

Ground 5: Dependent limitations (PEG-lipid, drug:lipid ratio, targeting, PK/stability)

• PEG-lipid / long circulation → Allen 1991 and the spec's own admission that PEG-lipid inclusion "is asserted to have a several-fold prolongation of the liposome blood circulation time." The neutral-PEG-lipid preference (PEG-DSG, PEG-ceramide) versus anionic PEG-DSPE is a material-selection choice among a small, known set of PEG-lipids.
• Targeting moiety / immunoliposome → immunoliposome art was mature well before 2004 (cf. the Hermes "Immunoliposomes for optimizing internalization" family, DE69736178 T2, which the search surfaced).
• Drug:lipid ratios, sizes, ≥24 h/≥48 h retention, ≥90% at 6 months → routine optimization, though this is where the patent's in vivo data (FIGS. 1–2, 5, 19–20) do the patentee's rebuttal work (below).

3. Element-by-element mapping (composition genus)

4. The patentee's rebuttal — and why it is strong

1. The art's own hierarchy pointed away from SOS. As of 2004 the camptothecin field favored citrate/pH gradients (Madden '008's preferred embodiment) and polymeric polyanions (dextran sulfate) — and the '213 examples show polyphosphate (a polyanion) and ammonium sulfate leak rapidly, while SOS retains drug for days. If the field's ranking of anions was opposite to what the patent found, that is evidence of non-obviousness, not mere optimization.
2. Unexpected, species-specific results. Haran's mechanism would predict that any impermeant multivalent anion improves retention; it would not predict the magnitude the patent reports, nor the 8:1 irinotecan:SOS intra-liposomal salt that forms. In re Soni-type superior/unexpected results are a recognized rebuttal to a KSR "obvious to try" attack.
3. The neutral-PEG finding arguably teaches away. The prevailing practice used anionic PEG-DSPE; the patent reports that anionic PEG-lipids degrade loading while neutral PEG-DSG/PEG-ceramide preserve it. If the art uniformly directed to PEG-DSPE, this is a legitimate In re O'Farrell-style teaching-away argument.
4. A tribunal has already rejected a § 103-equivalent attack. Teva opposed EP 1746976 (the EP member of WO2005107712) for lack of inventive step; the Opposition Division rejected the opposition and maintained the patent as granted, and the Board of Appeal dismissed Teva's appeal (per the Clarivate Current Patent Gazette, 2 June 2025). That is a considered, adverse-then-affirmed judgment on the same disclosure and substantially the same art — not binding in a U.S. court, but highly probative.
5. § 103(c) disqualification. Commonly owned Hermes/Merrimack material cannot be used in the obviousness combination.

5. Bottom line

• Genus-level and method-level claims (a liposome whose interior contains a substituted-ammonium salt of a polyanionized sugar/polyol, loaded by transmembrane ammonium gradient): a strong § 103 case exists on Madden US 6,465,008 in view of Haran 1993 (and Maurer-Spurej 1999), optionally with US 5,281,237/US 5,783,568. Motivation is a same-problem/same-mechanism combination, an express teaching to select the counterion by impermeability and salt-gelling capacity, and a finite, predictable candidate set — squarely KSR/Wands.
• The sucrose-octasulfate species claims (especially the SOS–irinotecan salt, '213 cl. 11): weaker for the challenger. The decisive question is whether the retention superiority over the art's own polyanions (dextran sulfate, polyphosphate) and over ammonium sulfate was predictable. The patent's comparative data and the EPO outcome suggest a genuine, non-obvious species selection — the classic "narrow species, unexpected property" posture that survives § 103.
• Net assessment: More likely than not, the broad genus/method claims are vulnerable to a Madden-'008-based § 103 challenge; the SOS-specific composition claims are likely to survive. This maps onto the D.N.J. ANDA action (3:24-cv-04991) I identified earlier — a generic defendant would most plausibly attack the genus claims and design around the SOS species.

Confidence: Moderate on the reference contents (Haran, Madden '008, and US 5,281,237/5,783,568 are verified from primary or supplied text). Low on the exact claim scope of '213 itself — the analysis should be re-run once the granted claims are pulled verbatim from USPTO PatentCenter.

Sources

• Supplied authoritative text: Google Patents US8329213B2 and family member AU2005240131C1 (claims 1, 19, 20, 51).
• Haran et al., Biochim. Biophys. Acta 1151(2):201–215 (1993) — https://pubmed.ncbi.nlm.nih.gov/[8373796](/patent/8373796)/
• Madden et al., US 6,465,008 B1 — https://patents.google.com/patent/US6465008 ; PDF text at patentimages.storage.googleapis.com/…/US6465008.pdf
• Maurer-Spurej et al., Biochim. Biophys. Acta 1416:1–10 (1999); Mayer/Bally/Cullis, BBA 857:123 (1986); Madden et al., Chem. Phys. Lipids 53:37 (1990) — citations verified via https://jpharmsci.org/ and PMC4931871
• Yang et al., Biomater. Sci. 7:419–428 (2019) (post-priority confirmation of SOS vs. ammonium sulfate/SBE-β-CD for irinotecan) — https://pubmed.ncbi.nlm.nih.gov/30500018/
• EP 1746976 / WO2005107712 opposition history — Clarivate Current Patent Gazette, 2 June 2025; Belgian patent register entry 721576338
• WO2017/066726 (SOS salt preparation, US 4,990,610) and JP7431419B2 (triethylammonium sucrose octasulfate scavenger) — patentimages.storage.googleapis.com

If you'd like, I can next (a) pull the verbatim '213 claims from USPTO PatentCenter, and (b) chart each granted claim against Ground 1 element-by-element.