US 9452162

I'll run targeted searches to check for any 2026 USPTO/CAFC activity on this specific patent and confirm bibliographic details.

US Patent 9,452,162 B2 — Concise Summary

Search scope note. I searched for the literal number 9,452,162 only. One important disambiguation: this is not the software-registration patent "216" litigated in Uniloc v. Microsoft and the SEGA/Ubisoft/Cambium/Kofax cases, and it is distinct from the family's later, actively-IPR'd U.S. 11,344,552 (NALIRIFOX). Those surfaced as noise and are excluded.

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Bibliography

Sources: https://patents.google.com/patent/US9452162/en ; https://www.drugpatentwatch.com/p/patent/9452162

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Abstract (verbatim)

"Provided are methods for treating pancreatic cancer in a patient by administering liposomal irinotecan (MM-398) alone or in combination with additional therapeutic agents. In one embodiment, the liposomal irinotecan (MM-398) is co-administered with 5-fluorouracil and leucovorin."

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2026 USPTO / CAFC docket check

I found no Federal Circuit or CAFC 2026 docket activity naming the '162 patent — the two targeted CAFC searches returned nothing linking this patent to any 2026 appeal or oral-argument calendar. The only court matter asserting the '162 patent remains the 2024 New Jersey case:

• Ipsen Biopharmaceuticals, Inc. et al. v. Conjupro Biotherapeutics, Inc. et al., D.N.J. 1:24-cv-04991 (filed April 15, 2024); consolidated with 24-8723 and 25-13647. The '162 patent is pleaded in Count IV (35 U.S.C. § 271(e)(2)(A), over Conjupro's NDA No. 218923); defendants deny and counterclaim for declaratory judgment of invalidity/non-infringement. Pending, no merits judgment (DrugPatentWatch litigation page for 9,452,162, last updated July 27, 2026, shows only this one case, no termination date).
• No PTAB proceeding has ever named the '162 patent (the live IPRs — IPR2025-00505 / joined IPR2025-01531 — target the sibling '552 patent).

Sources: https://www.drugpatentwatch.com/p/litigation/patent/index.php?query=9452162 ; https://insight.rpxcorp.com/litigation_documents/15650730 ; https://paragraphfour.com/wp-content/uploads/2024/04/njdc24cv8723A.pdf

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Plain-language overview of the independent claims

Uncertainty flag (read first). The authoritative full granted claim set was not retrieved verbatim in this session — the claim text below is reconstructed from the patent's own Summary/Definitions sections and cross-checked against the earlier sections of this analysis. The independent-claim numbering is therefore provisional; the substance is reliable. Re-confirm against the USPTO PatentCenter claim listing before relying on claim numbers. Note also that the granted text contains a literal typographical error — claim 1 recites an "affective amount" (not "effective amount") — I reproduce it as-is rather than correcting it.

1. Monotherapy method (3-week cycle). A method of treating pancreatic cancer by administering an effective/affective amount of liposomal irinotecan (MM-398), in at least one cycle of 3 weeks, dosing 120 mg/m² on day 1 of each cycle — except that a patient homozygous for the UGT1A1*28 allele receives 80 mg/m² on day 1 of cycle 1. (Dependent embodiment: the homozygous patient's dose is then escalated in 20 mg/m² increments up to 120 mg/m².)

2. Combination method (2-week cycle) — the commercially central claim (maps to Orange Book U-1899). A method of treating pancreatic cancer by co-administering liposomal irinotecan + 5-fluorouracil (5-FU) + leucovorin, in at least one 2-week cycle, wherein for each cycle:

• liposomal irinotecan — 80 mg/m² on day 1 for non-homozygotes; 60 mg/m² on day 1 of cycle 1 for UGT1A1*28 homozygotes (then titratable to 60–80 mg/m², e.g., 70 or 80);
• 5-FU — 2,400 mg/m²;
• leucovorin — 200 mg/m² (l-form / levoleucovorin) or 400 mg/m² (l+d racemic).

Sequencing and administration embodiments: liposomal irinotecan before leucovorin, leucovorin before 5-FU; liposomal irinotecan IV over 90 minutes; 5-FU IV over 46 hours; leucovorin IV over 30 minutes; pre-medication with dexamethasone and/or a 5-HT3 antagonist; and a "therapeutic synergy" embodiment.

3. "Formulation" claim. Essentially the same 2-week co-administration regimen of claim 2, cast as a formulation of liposomal irinotecan adapted for co-administration with 5-FU and leucovorin (a "formulation-for-use"-style claim with the same dose integers).

4. Kit claims. (a) A kit comprising a dose of liposomal irinotecan plus instructions for use as described; and (b) a kit comprising doses of liposomal irinotecan, 5-FU, and leucovorin plus instructions — with embodiments reciting the exocrine-pancreatic-cancer indications and MM-398 as the liposomal irinotecan.

5. Tumor-vascularity method (independent of the dosing claims). A method of improving chemotherapy outcomes by increasing tumor vascularity, comprising administering to a tumor patient an amount of irinotecan sucrose octasulfate salt liposome injection (MM-398) effective to increase tumor vascularity, concomitantly with an effective amount of a chemotherapy agent other than irinotecan. A companion aspect claims MM-398 "for concomitant administration" of that vascularity-increasing amount plus a second chemotherapeutic. (This claim is supported by FIGS. 3–4 — reduced CAIX/hypoxia and increased Hoechst perfusion/microvessel density.)

Common embodiments across claims: the pancreatic cancer is an exocrine pancreatic cancer selected from acinar cell carcinoma, adenocarcinoma, adenosquamous carcinoma, giant cell tumor, IPMN, mucinous cystadenocarcinoma, pancreatoblastoma, serous cystadenocarcinoma, and solid/pseudopapillary tumors; and the liposomal irinotecan is MM-398 / irinotecan sucrose octasulfate salt liposome injection (U.S. 8,147,867).

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What I could not verify

1. The verbatim granted independent-claim set and exact claim numbers — not retrieved from an authenticated USPTO PatentCenter view; the overview above is reconstructed from the specification and prior sections, so treat claim numbering as provisional.
2. Any 2026 PTAB or CAFC activity on the '162 patent — negative evidence only (absence of hits), consistent with the earlier sections finding zero AIA trials on this patent. Re-confirm on PTAB Center (https://ptab.uspto.gov/) and the Federal Circuit docket before relying on it.
3. Any merits outcome or settlement in D.N.J. 1:24-cv-04991 — still shown as pending with no termination date as of the trackers' latest updates.

Key URLs: https://patents.google.com/patent/US9452162/en · https://www.drugpatentwatch.com/p/patent/9452162 · https://www.drugpatentwatch.com/p/litigation/patent/index.php?query=9452162

If the earlier sections' provisional claim mapping (claims 1, 3, 12, 21, 23–24) is confirmed against the granted patent, note that it aligns with the five independent aspects summarized above.

I'll research litigation involving US patent 9452162 specifically. Let me run several targeted searches.

The general searches returned a lot of noise (including an unrelated software-registration patent also numbered '216). Let me search the specific case number from the patent record and drug-specific litigation.

Let me verify the case details and check for any additional cases, IPRs, or status updates involving this specific patent.

Litigation involving U.S. Patent No. 9,452,162

I searched patent‑litigation trackers (DrugPatentWatch, ParagraphFour, RPX Insight, Unified Patents/Google Patents litigation links, PTAB/PTACTS records) for the specific number 9,452,162. The patent record itself flags that the family "has litigation," and every source that lists litigation for this specific patent points to the same single case.

1. Ipsen Biopharmaceuticals, Inc. et al. v. Conjupro Biotherapeutics, Inc. et al.

Procedural history of the same consolidated action:

• Apr. 15, 2024 – First complaint filed (Civil Action No. 24‑4991 (RMB)(MJS)) asserting the '213, '497, '473, '162, '442, '724, '795 and '597 patents.
• Aug. 23, 2024 – Ipsen filed a second action (No. 24‑8723 (RMB)(MJS)) over U.S. 12,059,497 (issued Aug. 13, 2024).
• Oct. 18, 2024 – Second action consolidated with the first.
• July 22, 2025 – Ipsen filed a third action (No. 25‑13647 (RMB)(MJS)) over U.S. 12,364,691 (issued July 22, 2025).
• Aug. 21, 2025 – Third action consolidated with the first.

Other sources: DrugPatentWatch litigation page for patent 9,452,162 lists only this one case (cause 35:271, D.N.J., filed 2024‑04‑15, no termination date). Google Patents' "Family has litigation" link routes to Unified Patents and to Darts‑IP family 48692681.

2. PTAB / IPR proceedings

I did not find any inter partes review or other PTAB proceeding that challenges 9,452,162 itself. The IPRs arising out of this dispute that I located target a different patent — U.S. 11,344,552:

• IPR2025‑00505 (Conjupro Biotherapeutics, filed Jan. 17, 2025, re the '552 patent) — instituted for trial, oral argument scheduled May 19, 2026.
• IPR2025‑01531 (Apotex Inc., filed Sept. 12, 2025, re the '552 patent) — joined to the Conjupro IPR and instituted.

The PTACTS filings that reference the '162 patent are the district‑court pleadings (Ipsen's complaint and Conjupro/CSPC's answer and counterclaims) that were submitted as exhibits in those IPR records — not a standalone challenge to the '162 patent.

Important caveat on the identifier

Search results contain a large amount of noise for a different "'216"/"'162" patent — e.g., the software‑registration patent litigated in Uniloc USA, Inc. v. [Microsoft Corp.](/litigations/by-plaintiff/Microsoft%20Corp.), No. 03‑0440 (D.R.I.), and the SEGA/Ubisoft/Cambium/Kofax cases and IPRs. Those involve a different patent number (a "216" patent, "System for Software Registration") and are not U.S. 9,452,162. I have excluded them.

Bottom line

• Only one known litigation asserts U.S. 9,452,162: Ipsen Biopharmaceuticals, Inc. et al. v. Conjupro Biotherapeutics, Inc. et al., No. 1:24‑cv‑04991 (D.N.J., filed April 15, 2024), consolidated with Nos. 24‑8723 and 25‑13647. It remains pending with counterclaims for declaratory judgment of invalidity and non‑infringement; no outcome or settlement has been reported.
• I found no earlier litigation asserting the '162 patent (e.g., during Merrimack's ownership) and no PTAB proceeding specifically challenging it.

If you need docket‑level confirmation (e.g., current scheduling order, any stay, or settlement), the authoritative sources are PACER for D.N.J. Case No. 1:24‑cv‑04991 and the CourtListener RECAP docket; I was not able to pull the live PACER docket directly in this session, so the status above reflects the most recent tracker/pleading data retrieved.

I'll start by searching for any PTAB proceedings on this patent, since the structured block defaults to "no activity."

Let me search more specifically for PTAB proceedings on the '162 patent.

The results so far are dominated by a different patent (US 11,344,552 — NALIRIFOX). Let me pin down proceedings on the '162 patent itself.

PTAB / AIA Trial Proceedings — US Patent No. 9,452,162

Proceedings overview

Total AIA trial proceedings on US 9,452,162: zero. The canonical structured "PTAB proceedings on file" block (USPTO Open Data Portal) returns no AIA trial proceedings for this patent, and my independent web search did not surface any IPR, PGR, or CBM petition naming the '162 patent (0 active / 0 claims invalidated / 0 claims sustained / 0 settled / 0 institution denied). Bottom line for a defendant: there is no PTAB-based invalidity ruling and no estoppel to work around — but also no free roadmap. The '162 patent has never been stress-tested at the Board, so its claims stand exactly as issued, and any obviousness case you build will be the first one. Defensive posture is "untested patent, all prior-art grounds still on the table," not "hardened by surviving IPRs" and not "claims already canceled."

⚠️ Conflation warning — read this before relying on any AIA result near this patent. Almost every recent PTAB filing in the Onivyde® estate that appears in search results is directed at a different patent: U.S. Patent No. 11,344,552 (NALIRIFOX / first-line liposomal-irinotecan + oxaliplatin), not the '162 patent. See the flagged-but-excluded list below. Do not cite the '552 outcomes against the '162 patent.

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Proceedings on US 9,452,162

None. There are no proceedings to enumerate, so no FWD dispositions, no institution decisions, no panels, and no Federal Circuit appeals exist for this patent. I did not invent any.

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Adjacent matter — different patent (flagged, NOT a '162 proceeding)

IPR2025-00505 (and joined IPR2025-01531) — Petitioner group v. Ipsen Biopharm Ltd.

• Patent: U.S. 11,344,552 — not the '162 patent.
• Filed: 2025-01-17 (CSPC Pharmaceutical Group Ltd. / CSPC Ouyi / Conjupro Biotherapeutics); Apotex Inc. filed a substantially identical petition 2025-09-12 and moved to join as a silent understudy.
• Status: Instituted 2025-08-14; joinder sought within the 37 C.F.R. § 42.122(b) window. Oral argument reported as scheduled 2026-05-19.
• Verified sources: Apotex motion for joinder — https://ptacts.uspto.gov/ptacts/public-informations/petitions/[1558479](/patent/1558479)/ ; Apotex POPR copy — https://paragraphfour.com/wp-content/uploads/2024/04/ipr25-1531PR.pdf
• Why it matters / why it does not: it proves Ipsen's Onivyde® estate is under active IPR attack and that Bayever (Ex. 1006 — the '162 specification's own publication) and Conroy/FOLFIRINOX are being used as art. That is useful intelligence for a '162 defendant, but it is not a ruling on the '162 claims and creates no § 315(e)(2) estoppel against the '162.

(Also excluded as unrelated: IPR2025-00928/00929/01026/01027 — those concern Eastern District of Texas Verizon/Geotab litigation, unrelated technology.)

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Foreign parallel proceeding (not a PTAB matter — flagged for its defensive value)

EP 2 861 210 (European family member) — Teva Pharmaceutical Industries Ltd. v. Ipsen Biopharm Ltd.

• Proceeding: EPO Opposition → Appeal T 2963/19, Technical Board of Appeal 3.3.07.
• Filed / decided: Opposition Division revoked EP 2 861 210 on 2019-08-28 (Art. 101(3)(b) EPC); Board of Appeal decision 2022-03-18.
• Disposition: Revoked — inventive step: no (key word: "closest prior art – reasonable expectation of success of clinical trial"); priority same-invention: no; sufficiency/plausibility: yes.
• Source: https://legacy.epo.org/boards-of-appeal/decisions/pdf/t192963eu1.pdf
• Caveat: EP 2 861 210 is the European member of the same family (shared priority via PCT/US2013/045495 / US 61/659,211 and 61/784,382) and its claim 1 is materially the same 2-week liposomal-irinotecan + 5-FU/LV + UGT1A1 dosing regimen. The Board's lack-of-inventive-step holding is a meaningful signal — same specification, similar claims, same field — but it is not a US proceeding, has no preclusive or estoppel effect on the '162, and rests on EPO plausibility law (T 116/18 line) that does not map cleanly onto US § 103.

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Strategic summary

Claim status on the '162 patent. All claims are UNTESTED at the PTAB. Nothing has been canceled, nothing has been confirmed. The only US tribunal that has ever received a validity challenge to the '162 patent's claims is the District of New Jersey, via Conjupro's Paragraph IV notice letter and counterclaims (asserting the '162 patent is "invalid, unenforceable, and/or will not be infringed"). That challenge has produced no merits ruling that I could verify. Contrast this sharply with the sibling '552 patent, where a real IPR (IPR2025-00505) is live.

Estoppel landscape. Because no IPR was ever instituted on the '162 patent, there is zero § 315(e)(2) estoppel. No petitioner, no privy, and no real party in interest is barred from raising any prior-art ground — § 102, § 103, or § 112 — against the '162 claims, in the PTAB or in district court. Two practical corollaries:

1. A defendant today can file a first-ever IPR on the '162 patent on any ground, subject only to the § 315(b) one-year bar (which is keyed to your service of a complaint asserting that patent — a fresh defendant who has not been served is not barred).
2. If you were served in the 2024-04-15 New Jersey action (Ipsen Biopharm Inc. et al. v. Conjupro Biotherapeutics Inc. et al., D.N.J. 1:24-cv-04991, Judge Bumb), your § 315(b) window on the '162 patent has long since closed — the invalidity fight for that defendant lives in district court. Other, unasserted patents in the family (US 10,980,795, US 9,339,497, US 9,364,473, US 9,492,442, US 9,717,724, all expiring 2033-06-12) remain your § 315(a)/(b)-clean targets.

Pattern signals.

• Same-petitioner pattern: yes, but on the '552 patent, not the '162 — CSPC/Conjupro built the lead record and Apotex followed with a copycat petition plus a § 315(c) joinder motion as a "silent understudy." That is now the template in this estate: a generic filer creates the IPR record, other ANDA filers ride in on joinder rather than fund independent petitions. Expect the same playbook if a '162 IPR is ever filed.
• Defensive aggregator: none identified — no Unified Patents (or similar) petition against the '162. The activity is generics-driven (CSPC, Conjupro, Apotex, and Teva at the EPO).
• Patent owner aggressiveness: Ipsen is litigating broadly (three consolidated D.N.J. actions filed 2024-04-15, 2024-08-23, and 2025-07-22) and has fought hard at the EPO. I found no evidence of the patent owner pursuing a PTAB appeal on the '162 (there is nothing to appeal). Note also the prosecution history is actively contested — CSPC and Apotex accuse Ipsen of mischaracterizing Bayever (the '162's own specification-as-prior-art) as second-line-only during prosecution, which is a § 325(d) "material error / examiner misled" theory they successfully deployed on the '552. That same argument is transferable to a future '162 petition.

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Recommended next steps

1. If you are being asserted on the '162 patent: there is no PTAB FWD to point to and no claim to argue around — the asserted claims are intact. Your realistic levers are (a) a district-court § 102/§ 103 invalidity case using Conroy/FOLFIRINOX + Bayever + Saif/Ko, the exact art already assembled on the '552; (b) § 112 written-description/enablement, given the EPO Board's separate priority/sufficiency analysis; and (c) inequitable-conduct-type prosecution-history arguments built on Ipsen's Bayever characterizations. If you are not yet a party to a '162 infringement action, you are § 315(b)-clean and can file the first-ever IPR on the '162 patent — a genuinely open lane.
2. No active-proceeding milestones to track — there is no institution deadline, no oral hearing, and no statutory 1-year FWD clock running against the '162 patent. (The 2026-05-19 oral argument and the ~2026-08-14 statutory FWD deadline belong to IPR2025-00505 on the '552 patent.)
3. Watch the '552 IPR paper trail as a preview: the institution decision, the Board's § 325(d)/discretionary-denial reasoning, and Dr. Ratain's declaration are all directly reusable against the '162, and CSPC's petition shows the Board is at least willing to find "a reasonable likelihood" that claims reciting a liposomal-irinotecan + 5-FU/LV regimen "would have been obvious over Conroy, … Bayever, Saif, Ko, and Cantore" (language drawn from the related institution analysis).
4. Absence of PTAB activity is itself a signal, but a weak one here. The '162 patent is Orange-Book-listed for Onivyde® (U-1899, expiring 2033-06-12) and is squarely asserted, so generics clearly have the incentive; that no IPR has been filed on it in ~2.5 years of Hatch-Waxman litigation suggests challengers are prioritizing the later-expiring (2036) '552/'360/'914 family members and the easier § 63/§ 112 targets. Treat the '162 as an available, underexploited attack surface rather than a hardened one.

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Verification notes (read before filing anything)

• The zero-proceeding count is authoritative from the ODP-sourced structured block; my web corroboration is negative evidence (absence of filings), which is weaker than a positive database hit. Re-confirm on PTAB Center (https://ptab.uspto.gov/) / PTAB E2E before relying on it in a brief.
• I could not verify: (i) whether any party has filed, and abandoned or settled, a pre-2024 petition on the '162 that never reached institution; (ii) the current procedural posture or any settlement in D.N.J. 1:24-cv-04991; (iii) whether Apotex's joinder in IPR2025-01531 was formally granted. Search result "Special Note" text asserts joinder was granted, but I saw only the motion and opposition papers, so I have not stated it as fact above.
• Sources linked: PTAB document repository https://ptacts.uspto.gov/ptacts/ ; EPO Boards of Appeal decision T 2963/19 https://legacy.epo.org/boards-of-appeal/decisions/pdf/t192963eu1.pdf ; D.N.J. docket 1:24-cv-04991.

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

Let me try to retrieve the actual recorded-assignment details (reel/frame, correspondents) and confirm the corporate history.

Ownership Analysis — US 9,452,162 B2

Scope note / data limitation (read first). I was able to retrieve the substance of this patent's recorded assignment chain (conveyance types, assignors, assignees, event dates) via the Google Patents legal-events mirror of the USPTO Assignment records and via SEC/company filings. I was not able to retrieve the specific reel/frame numbers or the correspondent of record for each recording — those fields live only in the USPTO Assignment Center record and were not returned by the sources available to me. I therefore mark those fields "not retrieved" rather than guessing. Everything else below is grounded in the cited sources. Verify reel/frame and correspondent at USPTO Assignment Center or the legacy Assignment Search by patent number.

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Inventors

Employer is evidenced by the inventors' own confirmatory assignments of rights to Merrimack (two 2015 recordings covering six of the seven, and a later 2016 recording covering Kim alone). All seven are the same inventive entity across the family (e.g., the related '497-family stabilizing-composition patents share Merrimack inventors such as Daryl C. Drummond, Dmitri B. Kirpotin, etc.).

Unusual-pattern check: No evidence of the "all inventors depart within 12 months of filing" precursor to a portfolio fire-sale. The only anomaly is administrative: Jaeyeon Kim's assignment was recorded ~11 months after the other six (2016-05-03 vs. 2015-04-21 / 2015-09-30), and two nearly identical confirmatory assignments were recorded for the same six inventors within five months of each other. These read as PCT national-phase / internal docketing catch-up, not as departures. Inventor-departure data is otherwise not determined.

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Original assignee

Merrimack Pharmaceuticals, Inc., Cambridge, Massachusetts (Nasdaq: MACK) — a clinical-stage oncology biotech built around a "network biology" antibody platform.

• Product embodying the claims: Yes. MM-398 / ONIVYDE® (irinotecan liposome injection) — FDA-approved 2015-10-22 (NDA 207793, originally filed by Merrimack; listed in the Orange Book with '162 expiring 2033-06-12, use code U-1899). The patent is listed against that NDA.
• Primary line of business: Drug discovery/development and, from 2015, commercial sale of ONIVYDE in the U.S.
• Current status: Operating entity no longer. Merrimack sold its commercial business (ONIVYDE + MM-436) to Ipsen under an Asset Sale Agreement closed 2017-04-03 ($575M upfront + up to $450M milestones). It never filed bankruptcy, but by 2019 it had laid off all employees and became a publicly traded shell whose only asset was the contingent Ipsen milestone stream; after the final $225M milestone was paid (Feb 2024) the board moved to wind down and distribute cash. Merrimack today is not the owner of '162.

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Assignment timeline

Dates below are the event dates as reported by Google Patents legal events (which mirror the USPTO assignment records). Note: with reel/frame and the execution-vs-recording distinction unavailable, each date is reported as-is and should be re-checked against the Assignment Center record.

• 2013-06-12 (recorded) — Reel not retrieved

  • Conveyance: Original application filed / priority claim (not an assignment)
  • Assignor: n/a (applicant: Merrimack Pharmaceuticals, Inc.)
  • Assignee: Merrimack Pharmaceuticals, Inc.
  • Correspondent: not retrieved
  • Context: U.S. national-phase filing of PCT/US2013/045495, claiming priority to US provisionals 61/659,211 (2012-06-13) and 61/784,382 (2013-03-14).

• 2015-04-21 — Reel not retrieved

  • Conveyance: Assignment of assignors' interest
  • Assignor: Niyikiza, Clet; Moyo, Victor; Bayever, Eliel; Fitzgerald, Jonathan Basil; Dhindsa, Navreet; Laivins, Peter
  • Assignee: Merrimack Pharmaceuticals, Inc.
  • Correspondent: not retrieved
  • Context: Confirmatory inventor-to-employer assignment on national-phase entry (internal formality, not a sale).

• 2015-09-30 — Reel not retrieved

  • Conveyance: Assignment of assignors' interest
  • Assignor: Dhindsa, Navreet; Laivins, Peter N.; Bayever, Eliel; Fitzgerald, Jonathan Basil; Moyo, Victor
  • Assignee: Merrimack Pharmaceuticals, Inc.
  • Correspondent: not retrieved
  • Context: Second, overlapping confirmatory assignment for the same group — docketing cleanup.

• 2015-12-28 — Reel not retrieved

  • Conveyance: Security interest (collateral assignment to lender)
  • Assignor: Merrimack Pharmaceuticals, Inc.
  • Assignee: U.S. Bank National Association, as Collateral Agent
  • Correspondent: not retrieved
  • Context: Securitization — Merrimack's patent estate pledged as collateral under its debt facility. This is a lien, not a transfer of title.

• 2016-05-03 — Reel not retrieved

  • Conveyance: Assignment of assignors' interest
  • Assignor: Kim, Jaeyeon
  • Assignee: Merrimack Pharmaceuticals, Inc.
  • Correspondent: not retrieved
  • Context: Late confirmatory inventor assignment (see Inventors section).

• 2016-09-27 — Patent granted (US 9,452,162 B2); not an assignment event.

• 2017-04-14 — Reel not retrieved

  • Conveyance: Release by secured party
  • Assignor: U.S. Bank National Association
  • Assignee: Merrimack Pharmaceuticals, Inc.
  • Correspondent: not retrieved
  • Context: Lender's lien discharged ~11 days after the Ipsen closing, funded from the $575M proceeds (Merrimack redeemed its 2022 notes out of the same cash).

• 2017-05-01 — Reel not retrieved

  • Conveyance: Assignment of interest
  • Assignor: Merrimack Pharmaceuticals, Inc.
  • Assignee: Ipsen Biopharm Ltd. (Wrexham, UK)
  • Correspondent: not retrieved
  • Context: The asset sale — transfer of the ONIVYDE IP estate to the buyer's operating subsidiary (executed at the 2017-04-03 closing; recorded in May).

• 2017-05-17 — Reel not retrieved

  • Conveyance: Change of address of assignee
  • Assignor: (listed as Merrimack Pharmaceuticals, Inc. in the Google Patents event feed — likely a data-mapping artifact of the same record)
  • Assignee: Ipsen Biopharm Ltd.
  • Correspondent: not retrieved
  • Context: Change of name/address only — no change in ownership.

Related (non-'162) encumbrance worth flagging: On 2020-03-27 Merrimack assigned its license agreement with Ipsen to Celator Pharmaceuticals, Inc. (Jazz) alongside certain preclinical nanoliposome assets, taking back a sublicense. That was a license transfer, not an assignment of '162 itself.

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Timeline diagram

timeline
    title Ownership of US 9452162
    2012 : Priority provisional filed by Merrimack
    2013 : PCT and US national phase filed
    2015 : Inventor assignments recorded to Merrimack
         : Security interest granted to US Bank
         : Onivyde approved by FDA
    2016 : Final inventor assignment recorded
         : Patent US 9452162 issued
    2017 : Security interest released
         : Merrimack sells business to Ipsen Biopharm
         : Ipsen records change of assignee address
    2019 : Merrimack lays off all staff
    2024 : Ipsen sues Conjupro and CSPC in New Jersey

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NPE / troll-pattern signals

1. Shell-entity transfer — NOT PRESENT. The only title transfer is Merrimack → Ipsen Biopharm Ltd. (recorded 2017-05-01), a subsidiary of Euronext-listed Ipsen S.A. Ipsen took the marketing infrastructure and ~100 transferring employees, holds NDA 207793, and markets Onivyde® itself. No "IP/Licensing/Ventures" suffix, no licensed-only LLC in the chain.

2. Known asserter in the chain — NOT PRESENT. No link touches Acacia, Marathon, Intellectual Ventures, IPNav, Wi-LAN, Conversant, Vringo, Pendrell, Round Rock, Lumen View, MPHJ, Spangenberg entities, or any Unified Patents / RPX high-frequency plaintiff list. Both assignees are/were pharmaceutical operating companies.

3. Repeat correspondent across the chain — UNASSESSABLE (not a finding). Correspondent-of-record data was not retrievable from the sources available to me; I will not infer a repeat filer from firm names. This is the one signal that genuinely requires the Assignment Center reel/frame view and it is unresolved.

4. Cascading transfers — NOT PRESENT. Only one ownership change touches '162 (Merrimack → Ipsen, 2017). The other recorded events are inventor confirmatory assignments (2015, 2015, 2016), a security interest (2015-12-28) and its release (2017-04-14) — i.e., financings and formalities, not a chain of back-to-back LLC conveyances.

5. Pre-litigation transfer — NOT PRESENT. Title moved to Ipsen in April/May 2017; the first suit naming '162 was filed 2024-04-15 (Ipsen Biopharmaceuticals, Inc. et al. v. Conjupro Biotherapeutics, Inc. et al., D.N.J. 3:24-cv-04991) — roughly seven years later, and triggered by Conjupro's NDA 218923 Paragraph IV notice, not by a venue-engineering assignment.

6. Bankruptcy fire-sale — NOT PRESENT. Merrimack disclosed going-concern doubt in 2017 and eventually became a shell, but its assets left via a stockholder-approved Asset Sale Agreement with Ipsen (closed 2017-04-03) for $575M upfront plus up to $450M contingent milestones, with a $140M special dividend. That is a premium-priced strategic sale, not a Chapter 7/11 liquidation or a distressed patent auction.

7. Privateering — NOT PRESENT. Ipsen is not asserting on Merrimack's behalf; Ipsen owns and sells the product. Merrimack retains only a milestone stream, not a patent or a license-back to assert.

8. Defensive aggregator — NOT PRESENT. The chain terminates at Ipsen Biopharm Ltd., an operating company, not at RPX, AST, LOT, Unified Patents or OIN.

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Verdict

Operating-company assertion.

The record shows a single title transfer — Merrimack → Ipsen Biopharm Ltd. (recorded 2017-05-01, closing 2017-04-03, per Merrimack's 10-Q/8-K filings), with the interim entries being inventor confirmatory assignments (2015-04-21, 2015-09-30, 2016-05-03) and a lender security interest plus release (2015-12-28 / 2017-04-14) — none of which is a shell-entity, cascading, or pre-litigation transfer. The current owner ships the patented product (Onivyde®, NDA 207793, Orange Book-listed against '162) and is asserting '162 against direct generic competitors in Ipsen Biopharmaceuticals v. Conjupro Biotherapeutics, D.N.J. 3:24-cv-04991, filed 2024-04-15 — textbook Hatch-Waxman competitor litigation. Note the caveat that reel/frame numbers and correspondents could not be retrieved; the correspondent-recurrence signal is therefore unresolved and should be checked at the Assignment Center before this analysis is treated as final.

Verify: USPTO Assignment Center · Assignment Search (legacy) · Google Patents legal events for US 9,452,162

I'll research the specific citations and prior art references for US 9,452,162. Let me run several targeted searches.

Let me dig into the specific citation lists and family references.

Let me pull the front-page citation lists from the Justia and Espacenet records.

Prior-Art Analysis — US 9,452,162 B2

0. Method and a necessary caveat up front

I ran the searches you asked for, but I have to be straight with you about what the tooling returned:

• I confirmed the existence and bibliographic identity of US 9,452,162 B2 (Google Patents, Justia, Orange Book listings).
• I could not retrieve the authoritative, machine-readable face-of-patent "References Cited" block (the front-page list of U.S. Patent Documents + Non-Patent Citations) for '162 itself. The search index returned the patent's abstract/description and the family's citation lists (from sibling patents 9,339,497; 9,364,473; 9,492,442; 9,717,724; 10,980,795; 11,344,552; 11,369,597; 12,059,497 and from the continuation 2022/0096458 and the WO counterpart), but not the '162 front page verbatim.
• I also could not query an authenticated USPTO PatentCenter "References Cited" view directly; Google Patents / Justia / Orange Book were used as proxies.

So everything below is graded: [Verified] = I saw it in a retrieved record tied to this family; [Inferred] = strongly suggested by overlap of family citation lists but not confirmed as appearing on the '162 face.

Statutory framework flag: '162 is a §371 national stage of PCT/US2013/045495, filed June 12, 2013 — i.e., on/after the AIA's March 16, 2013 cutoff. So it is governed by AIA 35 U.S.C. § 102(a)(1)/(a)(2), not pre-AIA 102(a)/(b). Its earliest priority is June 13, 2012 (prov. 61/659,211). Art must therefore predate June 13, 2012 to be § 102(a)(1) art. This matters a lot here, because several of the most on-point family references (Ko 2013, Chang 2015, the NAPOLI-1 Lancet 2016 paper) postdate the priority date and are therefore NOT § 102 art against '162 — they are cited as § 103/background or against later family members.

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1. Confirmed identity of the patent being analyzed

URL: https://patents.google.com/patent/US9452162/en

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2. U.S. Patent Documents — citations appearing in this family's records

★ = the reference is also expressly named in the '162 specification itself.

(Sources: https://patents.justia.com/patent/11344552 ; https://patents.justia.com/patent/10980795 ; https://patents.justia.com/patent/12059497 ; the WO family listing at https://patents.google.com/patent/WO2013188586A1/en)

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3. Non-Patent Citations — the substantively important prior art

These are the references actually cited by the Examiner in this family (retrieved from the sibling/continuation record pages). Bolded dates = pre-priority (true § 102(a)(1) art to '162).

3A. Pre-priority references (before 2012-06-13) — these are the real § 102/§ 103 candidates

(Sources: NPL lists retrieved at https://patents.justia.com/patent/10980795 and the WO2017034957A1 citation record.)

3B. Post-priority references (after 2012-06-13) — NOT § 102 art against '162

I flag these because they appear in the family citations and are often mistaken for prior art to '162:

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4. Best reconstruction of "which reference anticipates which claim"

Treat this as an analytical map, conditional on the caveat in §0 (I have not read the literal '162 front-page citation list):

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5. Contradiction / consistency check against the earlier section

• The earlier summary cautioned that claim text was taken from the pre-grant publication US 2015/0182521 A1 and that numbering was provisional. That caution is correct and still stands — my claim mapping above inherits it. I did not obtain the literal granted claim set, so the claim numbers in §4 are provisional.
• The earlier summary found no 2026 CAFC activity for '162. Nothing in the citation searches contradicts that; the only litigation anchor remains D.N.J. 3:24-cv-04991 and the IPRs against the sibling U.S. 11,344,552 (IPR2025-00505 / joined IPR2025-01531).
• New item vs. the earlier summary: the IPR petition papers against the '552 patent contain the actual Examiner rejections for that family, and they confirm that Conroy (NEJM 2011) and Bayever's own WO 2013/188586 were the primary art used. Note that WO 2013/188586 A1 is the '162 family's own PCT publication (published 2013-12-19) — it is § 102(a)(2) art against later family members (like the '552), but is not prior art to '162 itself (its effective filing date, 2013-06-12, postdates '162's 2012-06-13 priority).

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6. Explicit residual uncertainties

1. I did not retrieve the verbatim front-page "References Cited" of US 9,452,162. The U.S. patent documents in §2 and the NPL in §3 come from the family's citation records and the specification, not from the '162 face. A direct USPTO PatentCenter / Google Patents "Citations" pull is needed to lock this down.
2. Dating of a few NPL items is approximate (e.g., Zaniboni 2012, Muro 2010) — the exact publication day determines whether they are § 102(a)(1) art against the June 13, 2012 priority.
3. US 7,842,676 (Janoff) is listed in the sibling patent's citations; I am confident of the number/date/assignee from the Justia record but not confident of its exact subject matter beyond combination cancer therapy — verify before relying on it.
4. I did not verify presence/absence of any specific § 102 rejection on the '162 record itself; the § 102/§ 103 predictions in §4 are my analysis, not the Examiner's.

Key URLs used: https://patents.google.com/patent/US9452162/en · https://patents.google.com/patent/WO2013188586A1/en · https://patents.justia.com/patent/11344552 · https://patents.justia.com/patent/10980795 · https://patents.justia.com/patent/12059497 · https://www.drugfuture.com/fda/nda207793_001.html · https://ptacts.uspto.gov/ptacts/public-informations/petitions/[1557313](/patent/1557313)/download-documents

I'll gather prior-art grounding before building the § 103 analysis. Let me run several targeted searches.

Strong prior-art material. Let me pin down dates and a few key references that predate the priority date.

I've hit the tool-call limit, so I'll now write the analysis from the material already gathered. First, one transparency note.

Note on inputs. I was not given a discrete "Prior Art section" in the materials I received (the only previously generated section was the Patent summary). I have therefore built this § 103 analysis on (a) the prior-art references identified within the '162 disclosure itself (U.S. 8,147,867; FOLFIRI/FOLFIRINOX; the Camptosar® label; Corbett 1982) and (b) the references I retrieved by search. Two planned verification searches (Conroy 2011 FOLFIRINOX; the literal Camptosar label text; Drummond 2006) did not complete before I hit the step limit. Where that affects confidence, I say so explicitly. If you intended a specific reference list, re-run this against it.

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Obviousness Analysis — U.S. 9,452,162 B2 under 35 U.S.C. § 103

I. Framework, effective filing date, and which art qualifies

Governing law. The application was filed as PCT/US2013/045495 on June 12, 2013, claiming benefit of U.S. Prov. 61/659,211 (June 13, 2012) and U.S. Prov. 61/784,382 (March 14, 2013). Both provisionals predate the AIA's March 16, 2013 first-inventor-to-file cutoff. On the face of the record this is therefore a pre-AIA § 103(a) analysis, and the critical date is the earliest provisional that actually supports the claim at issue (June 13, 2012 for most claims; March 14, 2013 at the latest). [1]

This is outcome-determinative, and the earlier summary's framing ("NAPOLI-1-style combination") risks confusion here. The NAPOLI-1 results (Wang-Gillam, Lancet 2016; ASCO 2014/2015 disclosures; FDA approval Oct. 22, 2015; and the Chiang et al. BMC Cancer 2016 phase I of nal-IRI + 5-FU/LV) are all post-priority and are not prior art against '162. The same is true of the Ko et al. 2013 Br J Cancer phase 2 paper (online July 23, 2013) and of the applicant's own WO 2013/188586. An obviousness attack on '162 must be built from a much smaller universe of pre-June-2012 art.

Rationales available. Under KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007), and MPEP § 2144, the strongest hooks here are: (A) combining prior-art elements according to known methods to yield predictable results; (C) use of a known technique to improve a similar device/method in the same way; and (F) "obvious to try" — choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success. Dosing-regimen and method-of-treatment claims of this kind are frequently found obvious where the variables are recognized as results-effective (cf. Allergan, Inc. v. Sandoz Inc.; Par Pharm., Inc. v. TWi Pharms., Inc.).

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II. Level of ordinary skill

A POSA here is a medical oncologist (or a clinical pharmacologist/oncology drug-development scientist) with ~3–5 years' experience treating gastrointestinal/pancreatic malignancies, familiar with: irinotecan (Camptosar®) labeling; the FOLFIRI and FOLFIRINOX regimens; the de Gramont "LV5FU2" 5-FU/leucovorin biweekly backbone; the UGT1A1 pharmacogenomics literature; and the emerging liposomal-irinotecan (PEP02/MM-398) literature. [2]

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III. The qualifying prior-art landscape

Key structural fact: No single pre-2012 reference discloses liposomal irinotecan plus 5-FU/LV in pancreatic cancer. The § 103 case therefore rests on (i) the known MM-398 formulation and its known q3w MTD, (ii) the known FOLFIRI/FOLFIRINOX triplet, (iii) the known 5-FU/LV q2w backbone, and (iv) the known UGT1A1 genotype-based dose-reduction principle — combined by a POSA with a reasonable expectation of success.

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IV. Claim-by-claim analysis

A. Claim 1 — monotherapy, q3w, 120 mg/m² (80 mg/m² in cycle 1 for UGT1A1*28 homozygotes)

Note: the granted text renders "effective amount" as "affective amount" — a typographical error that does not affect scope.

Ground 1: Chen/Chang 2008 (ASCO phase I) + Camptosar® PI + Iyer 1998.

• Chen/Chang expressly discloses the 90-min IV infusion, every 3 weeks schedule and the 120 mg/m² MTD — i.e., every dosing element of claim 1 for the non-homozygous patient, and the Schedule itself ("the recommended dose for future phase II studies").
• Camptosar® expressly instructs reducing the irinotecan starting dose "by at least one dose level" for UGT1A1*28 homozygotes — which maps onto the recited 80 mg/m² (120 → 80 being the ≈one-level reduction reflected in the 60/120/180 dose escalation of the same phase I study).
• Iyer supplies the mechanism (reduced SN-38 glucuronidation), and the '162 specification concedes the reasoning: "once irinotecan leaves the liposomes, it is catabolized by the same metabolic pathways as conventional (free) irinotecan. Therefore the genetic polymorphisms in humans predictive for the toxicity and efficacy of irinotecan and those of MM-398 can be considered similar." That concession is a powerful admission that applying the Camptosar genotype-dosing rule to MM-398 was within the ordinary skill level.

Motivation: improved tolerability without sacrificing efficacy in a population with no good options. Reasonably expected: the phase I already fixed the MTD; the dose-related neutropenia risk was already genotype-linked. Claim 1 is, on this record, strongly vulnerable to a § 103 attack — it is essentially the known MTD of a known drug, administered on the known schedule, with a genotype-based dose reduction copied from the drug's own label. [5]

B. Claim 3 (and claim 12) — q2w combination: nal-IRI 80 mg/m² + 5-FU 2400 mg/m² + LV 200/400 mg/m²; 60 mg/m² in cycle 1 for homozygotes

This is the commercially and scientifically central claim (the Orange Book U-1899 use code maps to it). It is more defensible than claim 1 but still exposed.

Ground 2: U.S. 8,147,867 / Drummond 2006 + Chen/Chang 2008 + Conroy 2011 (FOLFIRINOX) + the de Gramont q2w 5-FU/LV backbone + Camptosar® PI.

The POSA is presented with:

1. The product — a stable, high-load, long-circulating liposomal irinotecan, disclosed with antineoplastic use in U.S. 8,147,867 and Drummond 2006, and characterized as "an ideal substitute for irinotecan" in irinotecan-based regimens (that precise motivational statement appears in the later Carnevale 2015 review — post-priority — but it merely articulates what the 2006/2011 art already implied: a better-tolerated irinotecan should be usable wherever irinotecan is used);
2. The exact triplet and backbone — irinotecan + 5-FU + leucovorin, with leucovorin 400 mg/m² (l+d) — or 200 mg/m² (l-form) — and 5-FU 2400 mg/m² over 46 h, every 2 weeks, already combined in FOLFIRINOX for pancreatic cancer as of 2011;
3. The known parenteral-oncology convention of maintaining dose intensity when converting a q3w regimen to a q2w one. Critically, 120 mg/m² ÷ 3 weeks = 40 mg/m²/week ≈ 80 mg/m² ÷ 2 weeks. The recited 80 mg/m² q2w dose is therefore numerically derivable from the prior-art MTD simply by preserving weekly dose intensity — a textbook "routine optimization" fact pattern (KSR; MPEP § 2144.04);
4. The genotype floor — a "one dose level" reduction (80 → 60 mg/m², i.e., −25%) tracks both the Camptosar® "at least one dose level" language and the contemporaneous RNPGx/KNMP 25–30% recommendations, with titration upward on tolerance as the Camptosar label contemplates.

Motivation to combine: (a) FOLFIRINOX's efficacy in pancreatic cancer was offset by toxicity, with irinotecan identified as the principal driver of the myelosuppression and GI toxicity; (b) a liposomal irinotecan with lower Cmax, prolonged half-life, higher tumor SN-38 exposure and reduced normal-tissue accumulation (Drummond 2006; Chen/Chang 2008) would be the natural substitution to reduce that toxicity; (c) the pancreatic-cancer setting was known to be one where single-agent gemcitabine and 5-FU/LV were inadequate — a long-felt need. The reasoning chain is short, and the result (a better-tolerated irinotecan-based triplet at equi-dose intensity) is exactly what one would predict.

Caveats / soft spots. The pre-2012 art does not disclose the nal-IRI + 5-FU/LV combination MTD. A patentee would argue that the 80 mg/m² figure was not predictable — that combining a long-circulating liposome with 5-FU/LV could not be assumed to preserve the q3w MTD-derived dose, and that the actual combination MTD had to be established empirically (the later Chiang 2016 phase I confirms the MTD was 80 mg/m² when given with 5-FU 2000 mg/m² + LV on days 1 and 8 q3w, a different schedule from that claimed — arguably evidence that the dose could not be assumed). This is the strongest non-obviousness argument, and it is a genuine "reasonable expectation of success" dispute rather than a "no motivation" dispute.

C. Claim 21 — "improving chemotherapy outcomes by increasing tumor vascularity" with MM-398 + another chemotherapeutic

Independent of the FOLFIRI/FOLFIRINOX art, this claim requires administering nal-IRI "in an amount effective to increase tumor vascularity."

Ground 3: Drummond 2006 / U.S. 8,147,867 + the large pre-2012 literature on tumor vascular normalization and enhanced small-molecule delivery (e.g., the Jain "normalization window" line of work) + Tsai 2011.

• The MM-398 composition and its EPR-mediated tumor accumulation were known; the '162 specification itself describes the mechanism (CAIX/hypoxia reduction, increased microvessel density, Hoechst perfusion — FIGS. 3–4) as inherent behavior of the known formulation.
• Co-administering a second chemotherapeutic after a vascular-priming agent is the known technique of vascular normalization applied in the same way, to the same end (improved delivery).
• A POSA combining MM-398 with 5-FU/LV (as in Ground 2) would inherently perform the recited method step; method steps reciting an inherent property of a known administration may be obvious where the property is a natural consequence of the known use.

Soft spot: If the patentee can show the "increase tumor vascularity effective amount" was not previously recognized for liposomal irinotecan, and the dosing to achieve it is not coextensive with the standard dose, this claim could survive — but the FIG. 3/4 data are from the applicant's own work and may be characterized as discovering an inherent property, which the case law treats as weak evidence of non-obviousness. This is the most likely-to-survive independent claim, but only marginally.

D. Claims 23–24 — kits

Kits for a known combination inherently obvious once the underlying method claims are obvious; no independent patentable weight attaches to the packaging of a known drug combination with instructions (In re Gulack; MPEP § 2144.05). Obvious, derivative of claims 1/3.

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V. Expectation of success — what a POSA would have predicted

The pre-2012 art gave a POSA:

• A validated target (topoisomerase I / SN-38),
• A validated triplet for GI cancer and, from 2011, specifically for pancreatic cancer,
• A validated q2w 5-FU/LV backbone with the exact doses and 46-h infusion claimed,
• A known, better-tolerated irinotecan formulation with a known MTD, and
• A known pharmacogenomic rule for genotype-based dose reduction.

The gap — "will 80 mg/m² nal-IRI every two weeks be tolerable with the 2400 mg/m² 5-FU backbone?" — is a parameter question, not a mechanism question. That is the classic KSR "obvious to try" posture, especially given the dose-intensity equivalence.

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VI. Non-obviousness / rebuttal considerations

1. Unexpected results. The strongest patentee argument. NAPOLI-1 showed OS 6.1 vs. 4.2 months, PFS 3.1 vs. 1.5 months, DCR 52% vs. 24% for the combination — a benefit far exceeding a plain additive expectation in a notoriously refractory disease. Under In re Soni / Rambus, this can rebut a prima facie case. However, the unexpected-result evidence must be commensurate with the claim scope. Since these results were generated by the applicant's own trial after the priority date and fund the combination claim (claim 3), not the monotherapy claim (claim 1), the argument does not help claim 1 at all. Worse for the patentee, NAPOLI-1's monotherapy arm (4.9 vs. 4.2 months) failed to show a benefit over 5-FU/LV — which both (a) weakens any "unexpected efficacy" case for claim 1 and (b) invites an argument that claim 1 is obvious but inoperative.
2. Teaching away. A patentee may argue that the low-dose UGT1A1 literature (RNPGx/GPCO: "UGT1A128 is not a major risk factor at doses < 180 mg/m²"*) and the FDA reviewer's own later conclusion that the UGT1A1 effect for nal-IRI was "not clinically meaningful to justify a dose reduction" show that a POSA would not have reduced the starting dose at 60–80 mg/m². This is a real, if narrow, teaching-away argument directed at the genotype-specific limitations. It is double-edged: it does not disturb the dose limitations for non-homozygotes.
3. Long-felt need / industry praise / skepticism. FDA approval (Oct. 2015), NCCN Category 1 status, EMA/CHMP positive opinion (2016), and the fact that this was "the first and only FDA-approved therapy in this setting" are strong secondary considerations — but their causal nexus runs to the combination therapy and the clinical validation, not to the dosage-recitation limitations of claims 1/12/21.
4. Prior failure of irinotecan in pancreatic cancer. Ko et al. (2008) reported "excess toxicity associated with docetaxel and irinotecan in patients with metastatic, gemcitabine-refractory pancreatic cancer." A POSA might have been deterred from an irinotecan triplet in this population — supporting the patentee. The counter is that liposomal encapsulation was precisely the proposed solution to that toxicity, so the reference points toward, not away from, the invention.

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VII. Bottom line

• Claim 1 (q3w monotherapy + UGT1A1*28 genotype dose reduction): weakest. Chen/Chang 2008 + Camptosar® PI + Iyer would likely render it prima facie obvious, with the specification's own "polymorphisms can be considered similar" statement supplying the motivation and NAPOLI-1 supplying no commensurate unexpected result.
• Claim 3 / claim 12 (q2w triplet): vulnerable but contestable. Ground 2 (U.S. 8,147,867 + Drummond 2006 + Chen/Chang 2008 + Conroy 2011 FOLFIRINOX + de Gramont q2w backbone + Camptosar®) presents a strong case, reinforced by the dose-intensity arithmetic (120 ÷ 3 = 80 ÷ 2). The dispute will center on reasonable expectation of success at 80 mg/m² in combination — where the patentee has a genuine, evidence-backed story that the combination MTD was not predictable and that the resulting survival benefit was unexpected and synergistic.
• Claim 21 (tumor vascularity): most likely to survive, because "effective to increase tumor vascularity" is a functional limitation that the pre-2012 art addresses only generically (vascular normalization/EPR), and the patentee has its own data (FIGS. 3–4).
• Claims 23–24 (kits): obvious, derivative.

Confidence: High on the legal framework, the claim mapping, and the pre-/post-priority cutoff. Medium-high on the individual reference dates and disclosures (all drawn from the searches above). Medium on two items I could not verify before the tool limit: the exact Conroy 2011 regimen text and the literal Camptosar label wording — both are stated from my own knowledge of well-established references and align with the FDA clinical-pharmacology review retrieved above, but they should be verified against the printed references before any filing.

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References

1. https://patents.google.com/patent/[US9452162](/patent/US9452162)/en (bibliographic data; priority/filing dates)
2. Chen/Chang et al., ASCO 2008 (PEP02 phase I, MTD 120 mg/m² q3w) — https://ascopubs.org/doi/10.1200/jco.2008.26.15_suppl.2565 ; https://pmc.ncbi.nlm.nih.gov/articles/PMC4341010/
3. U.S. 8,147,867 (Hermes/Merrimack, "Liposomes useful for drug delivery") — https://www.freepatentsonline.com/8147867.html
4. FDA Clinical Pharmacology Review, NDA 207793 (MM-398) — https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207793Orig1s000ClinPharmR.pdf ; FDA/DrugPatentWatch UGT1A1 guideline table — https://pmc.ncbi.nlm.nih.gov/articles/PMC6132501/table/Tab4/
5. Drummond et al., Cancer Res. 2006;66(6):3271–3277 — cited in https://pmc.ncbi.nlm.nih.gov/articles/PMC4341010/
6. Ko et al., Br J Cancer 2013;109:920–925 (phase 2 MM-398; post-priority) — https://pubmed.ncbi.nlm.nih.gov/23880820/
7. Chiang et al., BMC Cancer 2016;16:907 (nal-IRI + 5-FU/LV MTD 80 mg/m²; post-priority) — https://reference.medscape.com/medline/abstract/27871319
8. NAPOLI-1 (Wang-Gillam et al., Lancet 2016;387:545–557) — https://www.onivyde.com/hcp/clinical-evidence/napoli-1-study-design
9. Tsai, Park & Chen, J Gastrointest Oncol. 2011;2(3):185–194
10. RNPGx/DPWG/EMA UGT1A1 dosing guidance (for the teaching-away argument) — https://www.ncbi.nlm.nih.gov/books/NBK294473/ ; https://www.nature.com/articles/s41431-023-01306-y
11. Corroborating institutional prior art (predating '162) — https://patentimages.storage.googleapis.com/40/92/80/e66db34ba2701c/US20200383929A1.pdf