US 11318098

I'll research this patent. Let me run several targeted searches.

Let me get the actual claim language and litigation details.

Let me find independent claim 18 and any CAFC 2026 activity.

US 11,318,098 B2 — Analyst Summary

Methodological note: My searches returned the Google Patents record for US11318098B2, the USPTO/report records, and federal court filings that quote the issued claims. The Google Patents text supplied in the prompt is truncated before the claims section, so the claim language below is grounded in court filings that reproduce the issued patent text (complaints, answers, and a Markman opinion) rather than in the patent's own claim column. Disclaimer: I found no Federal Circuit 2026 docket activity for this patent; treat all litigation status as of my search results.

1. Bibliographic data

Continuation chain (from the patent's cross-reference section): 17/329,755 ← 17/203,220 (Mar. 16, 2021) ← 16/576,587 (Sept. 19, 2019) ← 16/035,144 (Jul. 13, 2018) ← 15/299,413 (Oct. 20, 2016) ← 14/304,578 (Jun. 13, 2014; issued as US 9,504,651) ← 13/684,066 (Nov. 21, 2012; issued as US 9,492,386) ← 12/965,555 (Dec. 10, 2010; issued as US 8,329,070) ← 10/611,274 (Jun. 30, 2003; issued as US 7,901,708) ← provisional 60/392,887 (Jun. 28, 2002).

Discrepancy in the record (noted, not corrected): the Google Patents reassignment entry for the May 25, 2021 assignment lists assignors "GIESBRECHT, NOELLE; JEFFS, LLOYD; MACLACHLAN, IAN; PALMER, LORNE R.," whereas the printed patent front page (as reproduced in the D.N.J. filing) lists "Cory Giesbrecht." I am not able to resolve which spelling is correct.

2. Abstract (verbatim)

"The present invention provides apparatus and processes for producing liposomes. By providing a buffer solution in a first reservoir, and a lipid solution in a second reservoir, continuously diluting the lipid solution with the buffer solution in a mixing chamber produces a liposome. The lipid solution preferably comprises an organic solvent, such as a lower alkanol."

3. Independent claims — plain-language overview

Claim 1 — "A process for producing a lipid vesicle encapsulating a nucleic acid within the lipid vesicle…"

Quoted consistently across the Arbutus/Genevant complaints and Pfizer/BioNTech's admissions:

• Providing an aqueous solution including a nucleic acid in a first reservoir.
• Providing an organic lipid solution in a second reservoir, where the lipids are solubilized in a lower alkanol at about 75% v/v to 100% v/v.
• Introducing the aqueous solution and the organic lipid solution into a mixing chamber as opposing flows at about 180° relative to each other and at different flow rates relative to each other.
• Mixing the organic lipid solution with the aqueous solution, where the mixing instantaneously produces a lipid vesicle encapsulating the nucleic acid within the lipid vesicle by diluting the concentration of the lower alkanol in the organic lipid solution.

Plain language: Pump a water-based nucleic-acid solution and an ethanol-based lipid solution into a mixing chamber (e.g., a T-connector) from directly opposite directions — around 180° — but at unequal flow rates. When the streams meet, the abrupt drop in ethanol concentration makes lipid vesicles form essentially instantly, and the nucleic acid ends up trapped inside them. The critical numeric hook is that the lipid feed must be dissolved in a high-alkanol solvent (75–100% v/v), i.e., the precipitation/encapsulation happens out of a strongly alcoholic feed.

Claim 18 — second independent claim

Per the Acuitas DJ complaint (D.N.J. 3:23-cv-04200), the '098 patent "contains two independent claims, claims 1 and 18." The language attributed to claim 18 in the filings I found is:

• Introducing the organic lipid solution and the aqueous solution into a mixing chamber at different flow rates relative to each other and at an angle of between 90° and 180° relative to each other, and
• mixing such that the mixing instantaneously produces a lipid vesicle encapsulating the nucleic acid by diluting the concentration of the lower alkanol in the organic lipid solution.

Plain language (tentative): The same core manufacturing idea as claim 1, but with the geometry broadened from "about 180°" to any angle between 90° and 180°, while still requiring different flow rates between the two streams.

⚠️ Uncertainty I want to flag explicitly: the court filings are internally inconsistent about the statutory category of claim 18.

• One filing quotes language of the form "…the apparatus comprising: a first reservoir … a second reservoir … and a pump mechanism configured to pump …; wherein the mixing chamber is configured such that …" — i.e., apparatus language.
• Plaintiffs' counsel, in a hearing transcript in the D.N.J. case, characterized the family as: "the '320 patent … covers an apparatus for creating LNPs … and the '098 covers a process for doing that."
• A separate passage in the Acuitas complaint describes claim 18 as "claims a process for…" with the 90°–180° limitation.

Because the two descriptions cannot both be correct for the same claim, I do not have authoritative confirmation of whether claim 18 is an apparatus claim or a process claim. Verifying claim 18 directly against the printed patent's claim column (or the USPTO PatentCenter/Patent Public Search full text) is the right next step before relying on it.

Dependent claims (illustrative, from the reproduced text)

• Claim 2: the lipids comprise a phospholipid, cholesterol, a PEG-lipid, and a cationic lipid.
• Claim 8: the nucleic acid comprises an RNA.

4. Disclosure highlights (relevant to claim scope)

• Lipid formulation exemplified as DSPC : Chol : PEG-DSG : DODMA at ~20:45:10:25 mol; the family's related patents assert the four-lipid, specific-mol% concept.
• Two-stage stepwise dilution: vesicles formed in a high-alkanol environment (e.g., ~30–50% v/v ethanol after mixing), then stabilized by dilution to ≤25% (e.g., 19–25%) v/v.
• Encapsulation efficiency up to ~90% upon mixing; ~85% pDNA encapsulation reported for the process vs. ~5% for a conventional ethanol-drop method.
• Process/reported parameters: mixing rates ~60–80 mL/min at lab scale and 0.4–0.8 L/min at 1 L scale; low pressure (<10 psi); scalable 0.5 mL–5000 L; no static mixer or extrusion equipment required; non-turbulent flow (N_re < 2000) with shear rates ~500–3300/s.
• Nucleic acid encapsulation reported to occur within alkanol concentrations above ~22%.

5. Litigation / docket context (no CAFC 2026 docket found)

• Arbutus Pharma Corp. v. Pfizer Inc., D.N.J. Nos. 3:23-cv-01876 (also indexed as 2:23-cv-01876), filed April 4, 2023, asserting U.S. Pat. Nos. 9,504,651; 8,492,359; 11,141,378; 11,298,320; and 11,318,098 against Pfizer/BioNTech over the COVID-19 mRNA-LNP vaccine (COMIRNATY®). Accused instrumentality for the '098 count is the LNP manufacturing process using a "T-mixer."
• Acuitas Therapeutics Inc. v. Genevant Sciences GmbH & Arbutus Biopharma Corp., D.N.J. No. 3:23-cv-04200 (filed Aug. 4, 2023) — declaratory judgment of non-infringement/invalidity of the Arbutus patents, including the '098 patent. Counterclaims assert the '098 claims are invalid under §§ 102/103, and/or 112 (written description, enablement, indefiniteness — specifically as to "lower alkanol[s]," "flow rates," and "cationic lipid[s]").
• Related S.D.N.Y. Acuitas DJ action, No. 22-2229 (D.I. 1, Mar. 18, 2022) — the '098 patent was first identified to Pfizer/BioNTech in a June 3, 2022 Genevant email (the patent issued May 3, 2022).
• Claim construction: Markman hearing held Dec. 18, 2024 in the D.N.J. case; four disputed terms construed — "lipid vesicle," "fully encapsulated," "mol %," and "consisting essentially of." Arbutus disclosed a Sept. 9, 2025 claim construction ruling in the Pfizer/BioNTech action.
• No Federal Circuit 2026 appeal concerning the '098 patent appeared in my searches. The New Jersey docket links surfaced by Google Patents (3:23-cv-04200; 2:23-cv-01876 / 3:23-cv-01876) all point to the district-court matters above.

Practice point: Google Patents shows this patent as "Expired – Lifetime" with an anticipated expiration of 2023-06-30 and a terminal disclaimer. If accurate, the enforceable damages window is short (issuance May 2022 to mid-2023), which materially shapes the royalty theory in the pending cases. I could not independently verify the expiration calculation; it derives from the 20-year term measured from the June 30, 2003 parent filing plus the terminal disclaimer.

Canonical sources: https://patents.google.com/patent/US11318098/en ; https://uspto.report/patent/grant/11,318,098 ; https://investor.arbutusbio.com/news-releases/news-release-details/arbutus-biopharma-and-genevant-sciences-file-patent-0 ; https://www.bigmoleculewatch.com/wp-content/uploads/sites/2/2023/08/DNJ-3-23-cv-04200-1.pdf ; https://storage.courtlistener.com/recap/gov.uscourts.njd.[510890](/patent/510890)/gov.uscourts.njd.510890.1.0.pdf

I'll research litigation involving US Patent 11,318,098 using multiple sources.

Let me drill into the specific cases and docket details.

Let me verify additional details: the Moderna case, PTAB proceedings, and the current status/trial schedule.

Litigation involving US Patent No. 11,318,098 ("Liposomal apparatus and manufacturing methods")

Scope note / sourcing caveat: I searched litigation-oriented sources (Unified Patents litigation portal, CourtListener/RECAP, Docket Alarm, Big Molecule Watch, Goodwin, PatSnap Litigation, Arbutus SEC/investor disclosures). I did not auto-correct any patent number or case number below; identifiers are transcribed exactly as found. One inconsistency to flag up front: the system date supplied is April 26, 2026, but my search results returned documents dated through July 16, 2026 (e.g., an Arbutus press release). I have reported the later-dated material as found and flagged it, rather than silently reconciling the discrepancy.

Case 1 — Arbutus Pharma Corp. & Genevant Sciences GmbH v. Pfizer Inc. & BioNTech SE

Key grounding:

• Arbutus press release (April 4, 2023) naming the five patents and the District of New Jersey: https://investor.arbutusbio.com/node/17816/pdf
• Sept. 9, 2025 claim construction opinion (Dkt. 246) confirming the '098 Patent as one of five patents in suit, filed as an SEC exhibit: https://www.sec.gov/Archives/edgar/data/[1447028](/patent/1447028)/000117184325005815/exh_991.htm
• Counterclaimants' affirmative challenge to the '098 Patent includes Count XIII – Declaration of Patent Misuse ('098 Patent), dated July 10, 2023, plus invalidity counterclaims: https://storage.courtlistener.com/recap/gov.uscourts.nysd.[576814](/patent/576814)/gov.uscourts.nysd.576814.78.1.pdf
• Procedural history (answer July 10, 2023; Plaintiffs' answer to counterclaims Aug. 14, 2023; scheduling order Sept. 7, 2023; Markman hearing Dec. 18, 2024): https://investor.arbutusbio.com/static-files/f24c9cf7-dd55-412a-9f75-1f72bb476016
• Live docket activity in 2026 (motion to amend infringement contentions Dkt. 275, briefing Feb. 20, 2026; discovery letters March–May 2026): https://www.courtlistener.com/docket/67142175/arbutus-pharma-corp-v-pfizer-inc/

Google Patents indexing anomaly (do not merge these): the Google Patents page lists three New Jersey entries for this family — 3:23-cv-04200, 3:23-cv-01876, and 2:23-cv-01876. 3:23-cv-04200 is genuinely a different case (Case 2 below). 2:23-cv-01876 appears to be a duplicate/mis-indexed entry for 3:23-cv-01876 (division vs. office prefix), but I am flagging it rather than asserting that as fact. Source: https://patents.google.com/patent/[US11318098](/patent/US11318098)/en

Case 2 — Acuitas Therapeutics Inc. v. Genevant Sciences GmbH & Arbutus Biopharma Corp.

Key grounding:

• PatSnap Litigation record (filed 4 Aug 2023 – closed 20 May 2024; dismissed without prejudice; lists US11318098B2 among asserted patents): https://www.patsnap.com/resources/blog/litigation/acuitas-therapeutics-v-genevant-arbutus-lnp-patent-dispute-patsnap/
• AO120 Patent/Trademark Form listing "US 11,318,098 B2 – 5/3/2022 – PROTIVA BIOTHERAPEUTICS, INC.": https://www.courtlistener.com/docket/67667467/4/acuitas-therapeutics-inc-v-genevant-sciences-gmbh/
• Dismissal opinion: https://trellis.law/opinion/district/acuitas-therapeutics-inc-v-genevant-sciences-gmbh/369936488 ; also reported at VitalLaw (May 21, 2024): https://www.vitallaw.com/news/patent-d-n-j-acuitas-therapeutics-declaratory-judgment-suit-against-genevant-sciences-dismissed/

Predecessor SDNY action (does NOT appear to include the '098 patent): Acuitas's earlier DJ action, Acuitas Therapeutics Inc. v. Genevant Sciences GmbH, No. 1:22-cv-02229-MKV (S.D.N.Y.), was filed March 18, 2022, and was voluntarily dismissed on August 4, 2023 and refiled in New Jersey. Arbutus's own disclosure states that in the New Jersey refiling "Acuitas also added two additional patents to its New Jersey declaratory judgment action (U.S. Patent Nos. 11,298,320 and 11,318,098) that were not at issue in its New York action." That is consistent with the '098 patent having issued May 3, 2022 — after the SDNY complaint. Source: https://investor.arbutusbio.com/static-files/f1014a8e-fd6d-40b7-a1d7-9a8f38559fec

Litigation where the '098 patent does NOT appear to be asserted

Arbutus Biopharma Corp. & Genevant Sciences GmbH v. Moderna, Inc. — D. Del., Case No. 1:22-cv-00252, filed Feb. 28, 2022; settled under a March 2026 settlement agreement (Arbutus reporting ~$178M received July 8, 2026, plus a contingent $1.3B subject to a § 1498 Government-contractor appeal). The sources I found describe six patents asserted against Moderna (8,058,069; 8,822,668; 9,364,435; 9,006,417; 9,404,127; 9,518,272) — I found no indication that 11,318,098 was asserted in the Moderna action. I state this as a negative finding with moderate confidence; I could not complete a docket-level verification of every amended pleading. Sources: https://patentdocs.org/2026/03/13/quo-vadis-mrna-vaccine-technology-the-state-of-the-ip-lawsuits/ ; https://investor.arbutusbio.com/node/19581/pdf

Related 2026 international enforcement (family members, not US 11,318,098)

Announced July 16, 2026, Arbutus/Genevant filed three non-U.S. suits against Pfizer/BioNTech asserting different patents, reportedly as an expansion of the New Jersey proceeding:

• Canada — Federal Court of Canada File No. T-3200-26, asserting Canadian Patent No. 2,721,333
• UPC — Case PR-UPC-CFI-0002562/2026, asserting EP 4 241 767
• UPC — Case PR-UPC-CFI-0002566/2026, asserting EP 4 495 237

Source: https://investor.arbutusbio.com/node/19581/pdf. Caution: I have not verified that these foreign patents are exact counterparts of US 11,318,098, so I would not treat them as "'098 litigation."

Things I could NOT confirm

1. No PTAB proceedings identified. I did not find any IPR, PGR, or derivation proceeding against US 11,318,098. My search for a PTAB challenge was cut short, so treat this as unverified rather than affirmatively "no IPRs exist."
2. No USITC Section 337 investigation identified.
3. No CAFC appeal identified — consistent with Case 1 still being at the district-court stage.
4. Trial date for 3:23-cv-01876: none set in the materials I reviewed; Arbutus's disclosures state the court is "awaiting further scheduling."
5. EPO counterpart revocation: Arbutus's disclosures reference an EPO revocation decision it says will not affect the U.S. Pfizer/BioNTech litigation. This concerns a European family member, not US 11,318,098; I could not confirm which EP number.

Summary table

Sources for the family-level litigation index: Darts-IP family link on the Google Patents page (family 30000947) — https://patents.darts-ip.com/?family=30000947 — and the three New Jersey entries at https://patents.google.com/patent/US11318098/en (with the 2:23-cv-01876 duplicate caveat noted above).

I'll start by verifying the structured block against public sources, then chase down any AIA proceedings, decisions, and appeals tied to this patent.

Let me check specifically for any IPR/PGR petitions naming the '098 patent, and the sibling-patent PTAB activity.

No IPRs on the '098 so far — only district-court challenges. Let me confirm the sibling-patent PTAB history and double-check the Acuitas declaratory-judgment track.

PTAB / AIA Trial Landscape — US 11,318,098 B2

"Liposomal Apparatus and Manufacturing Methods" | Arbutus Biopharma Corp. (orig. Protiva Biotherapeutics, Inc.)
App. 17/329,755 (filed 2021-05-25) · Issued 2022-05-03 · Priority 2002-06-28 · Google Patents: https://patents.google.com/patent/US11318098/en

Proceedings overview

There are zero AIA trial proceedings on US 11,318,098. The USPTO Open Data Portal block for this patent returns no IPR, PGR, or CBM proceedings — active, settled, or terminated — meaning the breakdown is 0 active / 0 claims invalidated / 0 claims sustained / 0 settled / 0 institution denials, and a defendant today faces a completely untested patent at the PTAB: no claims have been canceled, none have been confirmed, and no § 315(e)(2) estoppel attaches to anyone — but the reason is almost certainly structural (see the § 112 point in the Strategic summary), not because the claims are ironclad. All validity attacks on the '098 to date are happening in district court, where Acuitas Therapeutics, Inc. has challenged independent claims 1 and 18 on § 102, § 103, and § 112 grounds in a declaratory-judgment action filed 2023-08-04 in D.N.J.

A caveat on sourcing: I found no IPR/PGR petition naming U.S. 11,318,098 in any public search, and the canonical ODP block agrees. I cannot prove a negative with certainty, so treat "no PTAB activity" as highly likely but not forensically verified. Notably, no AIA proceeding could now be filed by the two litigants most motivated to file one — see estoppel/time-bar analysis below.

Proceedings on the '098 patent

None — no AIA trial proceeding is on file

• Type: n/a (no IPR, no PGR, no CBM)
• Filed: n/a
• Status: The structured ODP data for US 11,318,098 lists no AIA trial proceedings as of the most recent ingest. No petition number is reported, and I will not manufacture one.
• Judge panel: n/a
• Petition grounds: n/a — but note that a PGR window on this patent closed on or about 2022-11-03 (nine months after the 2022-05-03 issue date). No PGR was filed. IPR remains theoretically available to any new, non-time-barred petitioner (expired patents can still be IPR'd for past-damages purposes).
• Institution decision: n/a
• Final Written Decision: n/a — no claim of the '098 patent has ever been canceled or confirmed by the Board.
• Settlement / termination: n/a
• Appeal: n/a at the PTAB. The only Federal Circuit activity in this family relates to a different patent (US 9,404,127), not the '098.
• Defensive value: Do not assume this patent has been vetted. Unlike its family relatives — including US 9,404,127, whose claims the Board held unpatentable and the Federal Circuit affirmed on 2023-04-11 — the '098 has never been through an adversarial validity trial at the Office. Its claims stand exactly as issued, and every invalidity ground is unexhausted.

Adjacent PTAB proceedings (same LNP family/portfolio — NOT directed to the '098 patent)

These matter for pattern analysis and § 325(d) risk, and I flag them precisely because they are frequently confused with the '098. None of these proceedings challenged the '098.

IPR2018-00739 / IPR2018-00680 / IPR2019-00554 — Moderna v. Arbutus (family portfolio)

• Type: Inter Partes Review
• Filed: 2018 (Moderna's first petition was filed 2018-02-21)
• Status: Terminated — decisions issued, patent-specific
• Petition grounds: § 102 and § 103 anticipation/obviousness over patents and printed publications, directed at Arbutus LNP composition/particle patents (not the '098's liposome-manufacturing process claims)
• Institution decision: The Board instituted in these proceedings (Arbutus filed Patent Owner Responses); institution dates vary by case and I did not verify each one against PTAB E2E
• Final Written Decision: The FWD outcomes differ across these three dockets and I have not verified claim-level results for each. Do not attribute cancellation to the '098 on the strength of these numbers.
• Settlement / termination: Not publicly settled as to the '098 (it was never a party)
• Appeal: One result in this campaign is confirmed: in the IPR against US 9,404,127, the Board held all claims invalid (FWD 2019-09-10 by Arbutus's own account), and the Federal Circuit affirmed on 2023-04-11. Source: Arbutus investor disclosure, https://investor.arbutusbio.com/static-files/b24c9cf7-dd55-412a-9f75-1f72bb476016
• Defensive value: This is the single most important signal in the family. Moderna already succeeded in wiping out one Arbutus LNP patent at the Board. The '098's escaping that fate is a function of timing and claim type, not of superior validity.

IPR2023-01358 and IPR2023-01359 — Pfizer/BioNTech v. Moderna (mirror-image posture, different patents)

• Type: Inter Partes Review
• Filed: 2023
• Status: FWD issued 2025-03-05 (public versions served 2025-03-12)
• Petition grounds: § 102/§ 103 against Moderna's patents US 10,702,600 and US 10,933,127 — Arbutus is not a party
• Final Written Decision: The Board invalidated the challenged claims (reported as the two Moderna patents being knocked out); Moderna has appealed to the Federal Circuit
• Appeal: Pending at the time of the March 2026 commentary
• Defensive value: Shows Pfizer/BioNTech are willing and able IPR petitioners — indeed they are the same parties being sued on the '098. Their decision not to file an IPR against the '098 is a deliberate litigation-strategy choice, not incapacity. Source: https://patentdocs.org/2026/03/13/quo-vadis-mrna-vaccine-technology-the-state-of-the-ip-lawsuits/

The real challenges to the '098 (non-PTAB, but where the action is)

Acuitas Therapeutics, Inc. v. Genevant Sciences GmbH & Arbutus Biopharma Corp. — D.N.J. No. 3:23-cv-04200

• Filed 2023-08-04; declaratory judgment of non-infringement and invalidity against ten Arbutus patents including the '098 (independent claims 1 and 18).
• § 102/§ 103 grounds pleaded: Quake et al., WO 2002/040874 (published 2002-05-23); Semple et al., WO 1998/051278 (published 1998-11-19); Semple et al., Efficient Encapsulation of Antisense Oligonucleotides in Lipid Vesicles Using Ionizable Aminolipids, 1510 Biochimica et Biophysica Acta 152 (2001).
• § 112 grounds pleaded: lack of written description and enablement because the specification does not describe/enable the claimed mRNA-LNP formulations, plus indefiniteness as to "lower alkanol," "flow rates," and "cationic lipid."
• Acuitas weaponizes Arbutus's own IPR arguments (from IPR2018-00739, IPR2018-00680, IPR2019-00554) that changing lipid proportions is "unpredictable" — used against the '098 as an admission on written description/enablement.
• Complaint: https://www.courtlistener.com/docket/67667467/1/acuitas-therapeutics-inc-v-genevant-sciences-gmbh/

Arbutus Biopharma Corp. et al. v. Pfizer Inc. & BioNTech SE — D.N.J. No. 3:23-cv-01876-ZNQ

• Filed 2023-04-04; asserts US 9,504,651; 8,492,359; 11,141,378; 11,298,320; and 11,318,098.
• Claim construction (Judge Quraishi) issued 2025-09-09, construing "lipid vesicle," "fully encapsulated," "mol %," and "consisting essentially of." Arbutus characterized the ruling as "generally favorable."
• Pfizer/BioNTech raised § 112 counterclaims attacking the '320/'098 as claiming subject matter (mixing at "different flow rates") never described in the specification — every figure and example in the 2002 priority document mixes at equal flow rates. Their counterclaims trace the '098 and '320 to applications 17/329,755 and 17/330,209 filed 2021-05-25, weeks after a 2021-03-31 CNN broadcast showed Pfizer's "T-mixer." Source: https://storage.courtlistener.com/recap/gov.uscourts.nysd.[576814](/patent/576814)/gov.uscourts.nysd.576814.78.0.pdf

Acuitas Therapeutics Inc. v. Genevant Sciences GmbH — S.D.N.Y. No. 1:22-cv-02229-MKV

• Filed 2022-03-18; the original DJ action. Notably did not include the '320 or '098 — those were added only in the later New Jersey filing.

Litigation portal links from the structured block: https://portal.unifiedpatents.com/litigation/New%20Jersey%20District%20Court/case/3%3A23-cv-04200 · https://portal.unifiedpatents.com/litigation/New%20Jersey%20District%20Court/case/3%3A23-cv-01876

Strategic summary

Claim status: everything is UNTESTED. Because no AIA trial ever reached the '098, there is no canceled/sustained ledger to work from. Independent claims 1 and 18 — the only two independent claims — stand as issued and are the whole ballgame; the remaining claims are dependents of one or the other. Claim 1 recites providing an aqueous nucleic-acid solution and an organic lipid solution wherein lipids are solubilized in lower alkanol at about 75% v/v to 100% v/v, and introducing the two into a mixing chamber as opposing flows at about 180° relative to each other and at different flow rates relative to each other. Claim 18 is the broader variant: opposing flows at an angle of between 90° and 180° and at different flow rates. No claim has been canceled, narrowed, or confirmed. The patent also carries a legal-status entry of "Expired – Lifetime" with an anticipated expiration of 2023-06-30 (20 years from the 2003-06-30 national-stage filing of the parent family), which means assertion now is a past-damages play under the six-year lookback, with essentially no injunction exposure.

Estoppel landscape: no IPR estoppel exists, but statutory bars have already closed the door on the obvious filers. No FWD means no § 315(e)(2) estoppel against anyone — a fresh defendant's prior-art grounds are fully available. But: (i) Pfizer/BioNTech were served with the N.J. complaint on/around 2023-04-04, so their § 315(b) one-year IPR window lapsed in April 2024 and they never filed; (ii) Acuitas filed its declaratory-judgment action first (S.D.N.Y. 2022-03-18 as to most patents; D.N.J. 2023-08-04 as to the '098), which triggers the § 315(a)(1) bar on an IPR petition by the same party (the § 315(a)(3) counterclaim carve-out does not save a plaintiff-filed DJ complaint). That is a strong structural explanation for the empty PTAB docket. A newly served defendant who was served less than one year ago, and who has not itself filed a DJ of invalidity, can still petition for IPR on the '098 — subject to § 325(d) discretionary-denial risk, since the Office has already seen much of this family's art in the '069/'435/'127 proceedings and in prosecution.

Pattern signals. Moderna ran a multi-petition IPR campaign against the Arbutus LNP portfolio (IPR2018-00739, IPR2018-00680, IPR2019-00554) and killed the '127 patent outright (FWD 2019-09-10; Fed. Cir. affirmed 2023-04-11). Pfizer/BioNTech are proven PTAB petitioners (IPR2023-01358/-01359, FWD 2025-03-05 invalidating two Moderna patents), yet chose not to petition against the '098. No defensive aggregator or Unified Patents-style filer appears anywhere in the chain — and note the structured block's "Family has litigation" Darts-IP link and the two New Jersey cases are prose-cutorial DJ/co-pending matters, not AIA filings. The patent owner (Arbutus) litigates aggressively but has not been forced to defend the '098 at the Board at all.

The single most important strategic observation: the '098's core vulnerability is § 112, and § 112 is not an IPR ground (35 U.S.C. § 311(b) limits IPR to § 102/§ 103 on patents and printed publications). The best attack on the '098 is that "different flow rates relative to each other" — the very limitation that distinguishes these claims from the rest of the family, all of which claimed "about equal flow rates" — is unsupported by a 2002 specification in which every disclosed example mixes at equal flow rates. That is a written-description/enablement fight for district court, and it is exactly the fight Acuitas and Pfizer/BioNTech are already running. It is also why no IPR was filed: the good arguments aren't IPR-eligible.

Recommended next steps

1. Lead with the negative. If you are a defendant and the demand letter cites the '098, the accurate statement is: no PTAB proceeding has ever been filed on this patent; no claim has been canceled; no estoppel exists; the patent is untested and carries a "Expired – Lifetime" status with anticipated expiration 2023-06-30. Do not accept any representation that the '098 "survived IPRs" — it never faced one. The PTAB decisions circulating in this portfolio (e.g., the '127 invalidity affirmance of 2023-04-11) are different patents.
2. If you were served within the last 12 months and have not filed a DJ action, an IPR remains available. Best-art candidates mirror those Acuitas pleaded: Quake WO 2002/040874 (2002-05-23) and Semple WO 1998/051278 (1998-11-19), plus T-mixer/microfluidic mixing literature published before 2002-06-28. Budget for a § 325(d) argument and be prepared to show the art is materially different from what the Office examined in the family IPRs and in prosecution.
3. If you are time-barred under § 315(b) (served before roughly 2025-10-01), your realistic path is a district-court § 112 case — written description/enablement/indefiniteness on "different flow rates relative to each other," "lower alkanol," and "flow rates." That is precisely the posture Acuitas and Pfizer/BioNTech have staked out, and the 2025-09-09 N.J. claim construction ruling is the current benchmark for those terms.
4. Monitor and cite the co-pending cases. Track D.N.J. 3:23-cv-01876-ZNQ (Arbutus v. Pfizer/BioNTech) and 3:23-cv-04200 (Acuitas v. Genevant/Arbutus). Any invalidity judgment on claims 1 and 18 in either forum is immediately useful defensive material; a judgment of validity would be a material upgrade to the patent's standing. PTAB E2E (https://ptab.uspto.gov) and CourtListener (https://www.courtlistener.com) are the right monitors.
5. Do not expect a late IPR. The patent is expired, the two most motivated challengers are both procedurally blocked or have elected to stay in district court, and no aggregator has engaged. If no petition appears within the next few months, the "no PTAB activity" status is likely permanent and your defense should be built for the district court, not the Board.

Verification caveat: proceeding numbers IPR2018-00739, IPR2018-00680, IPR2019-00554, IPR2023-01358 and IPR2023-01359 are quoted from the sources cited above; I did not independently confirm each docket's claim-level FWD outcomes or judge panels against PTAB E2E, and I have deliberately not attributed any specific claim cancellation in those cases to US 11,318,098.

I'll research the assignment record for US 11,318,098. Let me run targeted searches.

Key finding: the Acuitas complaint states "All the named inventors assigned the '098 patent to Protiva, which subsequently amalgamated into Arbutus." Let me dig into the corporate history and the recorded assignments.

Now let me look for the specific reel/frame records and any security interests or post-issuance transfers.

Assignment & Ownership Analysis — US 11,318,098 B2

Methodological note (read first): I reached my tool-call budget while trying to pull the raw Assignment Center records, so I could not retrieve the reel/frame numbers, execution dates, or correspondent-of-record fields for this patent. What follows is reconstructed from (a) the Google Patents "Legal Events / Reassignment" table for US11318098B2 (supplied in the prompt and re-checked), (b) federal court filings that repeatedly describe the ownership chain, and (c) PTAB mandatory notices and SEC filings describing the corporate succession. Where a field is unknown I say so rather than guess. Reel/frame and correspondent must be verified directly at the Assignment Center before this is relied on.

Inventors

Employment pattern: All four were Protiva Biotherapeutics employees when provisional 60/392,887 was filed (June 28, 2002). This is a classic single-employer inventor group — no "inventors scattering within 12 months" pattern. The Protiva group remained with the entity through the 2008 Tekmira acquisition; several Protiva-era inventors (Jeffs, Palmer, Yaworski) appear on later Arbutus/Protiva filings. (Note as a soft observation only: several inventors from this Protiva LNP cohort — including individuals named in the '098 family — later surface in materials connected to Acuitas Therapeutics, the Vancouver LNP company that is the* adverse DJ plaintiff** against Arbutus/Genevant in D.N.J. 3:23-cv-04200. I could not confirm specific current affiliations within my search budget and therefore do not treat this as a finding.)*

Original assignee

Protiva Biotherapeutics, Inc. (British Columbia, Canada) is the original assignee of the invention — the D.N.J. complaint states: "All the named inventors assigned the '098 patent to Protiva, which subsequently amalgamated into Arbutus." (https://www.bigmoleculewatch.com/wp-content/uploads/sites/2/2023/08/DNJ-3-23-cv-04200-1.pdf)

On the face of this particular certificate, however, the applicant/assignee is Arbutus Biopharma Corporation (the 2021 continuation was filed after the corporate succession completed). Google Patents lists Original and Current Assignee as Arbutus Biopharma Corp.

• Line of business: Protiva was a privately held biotech developing stable nucleic acid lipid particle (SNALP) / LNP delivery technology for siRNA. It was an operating R&D company, not a licensing shell — it earned Roche and Alnylam research agreements concurrent with its 2008 acquisition.
• Product embodying the claims: Protiva/Tekmira/Arbutus's LNP platform is a manufacturing/delivery technology, commercialized chiefly through licenses (e.g., Alnylam's ONPATTRO/patisiran) rather than as a branded end product owned by Arbutus.
• Current status: Operating. Arbutus Biopharma Corporation is a NASDAQ-listed (ABUS) clinical-stage biopharma. The predecessor chain: Protiva acquired by Tekmira (2008) → Tekmira renamed Arbutus (2015) → Protiva amalgamated into Arbutus (2018). Arbutus is not in bankruptcy.

Assignment timeline

⚠️ Data gap: The Assignment Center's reel/frame, execution date, and correspondent fields were not retrievable in this session (search budget exhausted). Below is the chain as recorded in the Google Patents Legal Events table, cross-checked against court/PTAB/SEC records. All entries are either corporate-succession events or the original inventor assignment — there is no recorded transfer to any third-party asserter, LLC, or defensive aggregator.

• Execution date not retrievable / recorded ~2021-05-25 — Reel unknown

  • Conveyance: Assignment of Assignors' Interest (see document for details)
  • Assignor: GIESBRECHT (NOELLE / "Cory" — see discrepancy above); JEFFS, LLOYD; MACLACHLAN, IAN; PALMER, LORNE R.
  • Assignee: PROTIVA BIOTHERAPEUTICS, INC.
  • Correspondent: Not retrieved (verify at Assignment Center — likely Arbutus's outside patent counsel of record)
  • Context: Original inventor → employer assignment (the underlying nunc-pro-tunc vesting assignment; re-recorded against the new continuation application in 2021).

• Effective 2008-05-30 (execution); recordation date not separately retrieved — Reel unknown

  • Conveyance: Stock acquisition / business combination — not a patent assignment of record (shared purchase; title to the patents remained with Protiva as a wholly owned subsidiary of Tekmira)
  • Assignor: Protiva shareholders
  • Assignee: Tekmira Pharmaceuticals Corporation
  • Context: Acquisition — patent title unchanged; Protiva became a wholly-owned subsidiary.

• Effective 2015-07-31 (announced 2015-07-20); ~2015 — Reel unknown

  • Conveyance: Change of Name (Tekmira Pharmaceuticals Corporation → Arbutus Biopharma Corporation)
  • Context: Change of name only — no change in title.

• Effective 2018-01-01 (recorded January 2018); mirrors the 2021-05-25 Google Patents entry — Reel unknown

  • Conveyance: Merger (amalgamation)
  • Assignor: PROTIVA BIOTHERAPEUTICS INC.
  • Assignee: ARBUTUS BIOPHARMA CORPORATION
  • Correspondent: Not retrieved
  • Context: Internal corporate reorg / vertical amalgamation — Protiva merged into its parent (confirmed by PTAB mandatory notices in IPR2019-00554 and IPR2018-00739: "Protiva Biotherapeutics, Inc. … was amalgamated into Arbutus Biopharma Corporation in January 2018." https://ptacts.uspto.gov/ptacts/public-informations/petitions/[1522819](/patent/1522819)/...).

• 2021-05-25 — Reel unknown

  • Conveyance: Merger (re-recorded against continuation application 17/329,755)
  • Assignor: PROTIVA BIOTHERAPEUTICS INC. → Assignee: ARBUTUS BIOPHARMA CORPORATION
  • Context: Clean-up recording filed coincident with the May 25, 2021 continuation filing to show an unbroken chain of title on the new application.

• 2022-05-03 — Patent issues to Arbutus Biopharma Corporation (no assignment; grant event).

• 2023-06-30 — Anticipated expiration (terminal disclaimer); Google Patents status "Expired – Lifetime."

License (NOT an assignment — do not mistake for a transfer): Arbutus granted Genevant Sciences exclusive rights to the asserted LNP patents. Per the Arbutus/Genevant complaint: "All are assigned to and owned by Arbutus, and, at all times since Arbutus and Genevant entered into a license agreement, Genevant has held Exclusive Rights to all of the Asserted Patents." Record title stayed with Arbutus; no assignment to Genevant is recorded. (https://storage.courtlistener.com/recap/gov.uscourts.njd.[510890](/patent/510890)/gov.uscourts.njd.510890.1.0.pdf)

Timeline diagram

timeline
    title Ownership of US 11318098
    2002 : Provisional filed by Protiva team
    2003 : Nonprovisional filed
         : Inventors assign to Protiva
    2008 : Tekmira acquires Protiva
    2015 : Tekmira renamed Arbutus Biopharma
    2018 : Protiva amalgamated into Arbutus
    2021 : Continuation filed and re-recorded
    2022 : Patent 11318098 issues
    2023 : Suits filed v Pfizer BioNTech
         : Acuitas DJ action filed

NPE / troll-pattern signals

1. Shell-entity transfer — NOT PRESENT. Every recorded link is a corporate-succession event between named operating companies (Protiva → Tekmira → Arbutus). No "IP Holdings / Licensing / Ventures" LLC; no registered-agent service address; no single-purpose Delaware/Texas LLC appears anywhere in the chain.
2. Known asserter in the chain — NOT PRESENT. Current assignee Arbutus Biopharma Corp (NASDAQ: ABUS) is an operating biopharma. Co-plaintiff Genevant Sciences is a licensing company but is an Arbutus affiliate, not on the enumerations you listed (Acacia, Marathon, IV, Wi-LAN, Conversant, Pendrell, Round Rock, etc.). Neither appears in the Unified Patents / RPX high-frequency plaintiff lists on the records I saw.
3. Repeat correspondent across the chain — UNKNOWN / no finding. The correspondent-of-record fields could not be retrieved. Since there are only two recorded conveyance events (both corporate succession) and no third-party transfers, the recurrence trigger cannot be met on the available record. Not a finding pending Assignment Center verification.
4. Cascading transfers — NOT PRESENT. Only two recorded events across ~20 years, both intra-corporate (2008 acquisition, 2018 amalgamation). No chained LLCs in <24 months; no shared-correspondent cluster.
5. Pre-litigation transfer — NOT PRESENT. The last title event is January 2018 (amalgamation) — ~5 years before the first suit (April 2023). The May 25, 2021 recording is a re-recordation coincident with a continuation filing (23 months before suit), not a transfer to an asserter. No transfer within the 6-month window.
6. Bankruptcy fire-sale — NOT PRESENT. No Chapter 7/11 proceeding; Arbutus is a solvent, publicly traded operating company.
7. Privateering — NOT PRESENT (with a note). Arbutus contributes LNP IP rights to Genevant, and both sue together. Classic privateering is an operating company staying behind while an NPE asserts on its behalf; here the operating originator is a named co-plaintiff and retains record title. The Genevant exclusive-license arrangement is best characterized as a commercial licensing JV, not privateering.
8. Defensive aggregator (anti-NPE) — NOT PRESENT. The chain does not terminate at RPX, AST, LOT, Unified, or OIN. The patent remains owned by the original developer and is actively asserted.

Verdict

Operating-company assertion.

Justification: The record title chain runs inventor → Protiva Biotherapeutics → (2008 acquisition) → Tekmira/Arbutus → (January 2018 amalgamation) → Arbutus Biopharma Corporation, with no transfer to any shell LLC, NPE, or defensive aggregator (only two recorded conveyances, both corporate succession). The current owner is the original R&D developer — a NASDAQ-listed operating biopharma — and it is suing actual competitors (Pfizer/BioNTech over COMIRNATY's LNP, D.N.J. 3:23-cv-01876) alongside its exclusive licensee Genevant, which is the opposite of the anonymous-shell pattern. The only "NPE-adjacent" feature is that Arbutus monetizes the platform largely through licensing (Genevant holds exclusive rights; Alnylam is a licensee) rather than a branded product — but that is a licensing model, not a troll pattern, and record ownership never left the developer.

Two caveats I will not paper over: (1) Reel/frame, execution dates, and correspondent-of-record were not retrieved and must be confirmed at the USPTO Assignment Center — search by patent number 11318098 at https://assignmentcenter.uspto.gov/ (or https://assignment.uspto.gov/patent/index.html). (2) The "Expired – Lifetime" / 2023-06-30 status and the terminal disclaimer, if accurate, sharply limit the enforceability window and thus the damages theory — but I could not independently verify that calculation in this session.

I'll research the prior art citations for US 11,318,098. Let me run several targeted searches.

Let me search for the specific prior art cited on the '098 patent's front page.

Let me look for the actual front-page references cited on the '098 patent and the related WO/EP family search reports.

I was unable to complete a final verification search (I hit the tool-step limit), so I'll give you a grounded analysis with the verification status made explicit for each item.

Prior-Art Analysis — US 11,318,098 B2 ("Liposomal apparatus and manufacturing methods")

Methodological note (read first). The Google Patents full text supplied in this task is truncated before the "References Cited" front-page block, and my searches did not return the '098 patent's own front-page citation list (I could retrieve the specification's discussion of prior art and family-level search reports, but not the examiner's PTO-1449 / front-page "U.S. Patent Documents" column for 11,318,098). I therefore cannot certify that the list below is the complete set of references cited on the '098 patent's face. What I can ground — and what I present below — is (a) the references the '098 specification itself cites and distinguishes, and (b) field-art references appearing in the closely related family's search reports. Items I could not verify against the '098 front page are flagged as such. I have not fabricated any citation.

Statutory framework. The '098 patent claims priority to U.S. Provisional 60/392,887 (June 28, 2002). If the issued claims are supported by that disclosure, the operative statute is pre-AIA 35 U.S.C. § 102. That matters for dating: references published more than one year before June 28, 2002 are § 102(b) art; references published within the year before (July 2001–June 2002) are § 102(a) art. (My prior section flagged a terminal disclaimer and a 2023-06-30 expiration — that affects enforceability/damages, not the § 102 analysis.)

1. References cited within the '098 specification (grounded, verbatim in the record)

These two are the only prior-art documents the '098 specification discusses by name. Both are in the "Background of the Invention" and both are expressly distinguished.

1a. U.S. Pat. No. 5,478,860 — Wheeler et al.

• Full citation: U.S. Pat. No. 5,478,860, "Microemulsion compositions for the delivery of hydrophobic compounds," Wheeler et al., issued Dec. 26, 1995.
• Description (per the '098 text): Discloses microemulsion compositions for delivering hydrophobic compounds (therapeutic drugs), plus in vitro and in vivo delivery methods. The '098 specification notes these are microemulsions — i.e., a lipid monolayer surrounding an oil-based core — rather than bilayer liposomes encapsulating a nucleic-acid payload.
• § 102 assessment: § 102(b) art (issued well over a year before the 2002 priority date). It is not anticipating of independent claims 1 or 18, because those claims require a lipid vesicle encapsulating a nucleic acid formed by mixing an aqueous nucleic-acid solution with an organic lipid solution in a lower alkanol at 75–100% v/v, at a defined angle and at different flow rates. A hydrophobic-compound microemulsion teaches none of those limitations. At most it is § 103 background art.

1b. PCT Publication WO 01/05373 — Knopov et al.

• Full citation: PCT Publication WO 01/05373 A1, Knopov et al., published July 26, 2001.
• Description (per the '098 text): Discloses preparing lipid vesicles by an ethanol-injection-type process using a static mixer that creates a turbulent environment (Reynolds numbers >2000); therapeutic agents are loaded after vesicle formation.
• § 102 assessment: Because it published July 26, 2001 — inside the one-year window before the June 28, 2002 priority date — it is § 102(a)/(e) art (not § 102(b)). This is the closest prior art in the record and the most plausible § 102 candidate, but on its face it still does not anticipate claims 1 or 18: the '098 claims require (i) the therapeutic agent present coincident with vesicle formation (not post-loaded), (ii) opposite flows at about 180° (claim 1) or 90°–180° (claim 18) at different flow rates, and (iii) — per the '098's own characterization — non-turbulent mixing. WO 01/05373's static mixer/turbulent flow and post-loading steps are the very features the '098 touts as not required. Realistically WO 01/05373 is a § 103 reference, not a § 102 anticipation. (Note the internal-consistency caution from my earlier section: I still could not authoritatively confirm whether claim 18 is an apparatus claim or a process claim, so the anticipation mapping for claim 18 is provisional.)

2. Field-art references in the related family's search reports (grounded, but not confirmed as '098 front-page citations)

These surfaced in search reports for sibling/related liposome-production patents and are the sort of art the '098 examiner would have considered. I include them because they are the technically relevant prior art, but I flag that I have not confirmed they appear on the '098 front page.

(Note: the Micro-Pak/Liposome Technology/Optime references appeared in the search report associated with EP 1 203 614, a liposome-production case — I am relaying them as the relevant field art, not asserting they are on the '098 face.)

3. Family-level non-patent literature (examiner/applicant cited in the '651 sibling — shared spec)

The '098 shares its specification with US 9,504,651 ("Lipid compositions for nucleic acid delivery"). That sibling's citation list includes NPL that, because the disclosures overlap, is likely also relevant to the '098's enablement/§ 102/§ 103 analysis. Representative items (flag: verified for the '651, not the '098):

• Batzri & Korn, "Single Bilayer Liposomes Prepared without Sonication," Biochim. Biophys. Acta 298:1015–1019 (1973) — the foundational ethanol-injection/dilution method. This is the origin of the very "conventional ethanol dilution" the '098 specification criticizes (dropwise addition producing heterogeneous unilamellar/multilamellar mixtures). Strong § 102(b) background art for the generic ethanol-dilution step; not anticipating of claims 1/18.
• Lasic, D.D., "Novel applications of Liposomes," Tibtech 16:307–321 (1998) — cited by examiner.
• Meyer, O. et al., "Cationic liposomes coated with polyethylene glycol as carriers for oligonucleotides," J. Biol. Chem. 273:15621–15627 (1998) — cited by examiner; PEG-lipid/nucleic-acid carrier art.

These are § 102(b) art on the general concepts (ethanol injection, PEG-lipid nucleic-acid carriers) but do not disclose the '098's claimed process/apparatus combination.

4. What I could not verify

• The complete front-page "U.S. Patent Documents / Foreign Patent Documents / Other Publications" citation list for US 11,318,098 B2 itself. This should be checked directly against PatentCenter / Patent Public Search (uspto.gov) or the granted-PDF front page (patentimages.storage.googleapis.com).
• Whether claim 18 is an apparatus claim or a process claim (unresolved in my earlier section; it changes which references map to it).
• Whether the '098's claims were amended during prosecution into the "different flow rates" / "about 180°" / "75–100% v/v lower alkanol" limitations now seen in the court filings — that history drives which earlier references are § 102 vs. § 103.

5. Bottom line

On the record I can substantiate, none of the cited references squarely anticipates independent claims 1 or 18 under § 102. The two references the patent itself identifies — Wheeler U.S. 5,478,860 (§ 102(b)) and Knopov WO 01/05373 (§ 102(a)/(e)) — each teach only sub-parts of the claimed combination (microemulsions; and turbulent-static-mixer ethanol injection with post-loading, respectively), leaving the key limitations (coincident nucleic-acid encapsulation; ~180° or 90°–180° opposing flows at unequal flow rates; 75–100% v/v lower alkanol feed) untaught. The realistic invalidity theory is § 103 (e.g., WO 01/05373 in view of Batzri 1973 / a T-mixer art reference), not § 102 — which is consistent with the Acuitas counterclaims pleading §§ 102/103 and 112 as alternatives.

Recommended next step: pull the '098 granted PDF front page and the application's complete file history (17/329,755 → parent chain) to (a) enumerate the exact cited references, and (b) confirm the claim-18 statutory category — both of which I flagged as unverified above.

Canonical sources used: https://patents.google.com/patent/[US11318098B2](/patent/US11318098B2)/en ; https://patents.google.com/patent/[US7901708B2](/patent/US7901708B2)/en ; https://www.freepatentsonline.com/y2021/0267891.html ; https://uspto.report/patent/grant/[9,504,651](/patent/9504651) ; https://patents.google.com/patent/EP1203614/en

I'll research the prior art of record and the litigation/IPR history for this patent family.

Let me dig into the specific prior art references identified against this patent and any IPR activity.

Obviousness Analysis — U.S. Patent No. 11,318,098 B2 (35 U.S.C. § 103)

Analyst note on inputs. The instruction was to "use the results from the Prior Art section of this page." The Google Patents page text supplied in the prompt is truncated before the claim column and does not render a discrete "Prior Art" section; it supplies only the "Prior art keywords" field (lipid; solution; vesicles; aqueous solution; organic) and the "Prior art date" (2002-06-28). I have therefore reconstructed the prior-art record from (a) the references cited on the face of the '098 patent as reproduced in the D.N.J. complaint exhibit, (b) the references discussed in the '098's own Background of the Invention, and (c) the invalidity contentions asserted against the '098 in the Acuitas DJ actions. Where I could not verify a reference's contents, I say so. Claim language is taken from the previously-generated section of this analysis (grounded in the D.N.J./S.D.N.Y. filings), not re-derived here.

1. The claims to be analyzed and the governing law

Claim 1 (process): providing an aqueous solution including a nucleic acid in a first reservoir; providing an organic lipid solution in a second reservoir with lipids solubilized in a lower alkanol at about 75% v/v to 100% v/v; introducing both into a mixing chamber as opposing flows at about 180° relative to each other and at different flow rates relative to each other; and mixing such that mixing instantaneously produces a lipid vesicle encapsulating the nucleic acid by diluting the alkanol concentration.

Claim 18 (second independent claim): same core, but with the angle broadened to 90°–180° and the "different flow rates" requirement retained.

Dependent claims include claim 2 (phospholipid + cholesterol + PEG-lipid + cationic lipid) and claim 8 (nucleic acid = RNA).

1.1 Which § 103 applies — and why it is the pivot of the whole case

The '098 issued May 3, 2022 from an application filed May 25, 2021, but sits at the end of an unbroken continuation chain to Ser. No. 10/611,274 (filed June 30, 2003) and provisional 60/392,887 (June 28, 2002). Two consequences follow:

• If the claims are entitled to the 2002/2003 date, pre-AIA § 102/§ 103 govern and prior art must predate June 30, 2002 to be § 102(b) art. On that footing, the entire post-2004 body of Arbutus's own published work — including the published parent application, U.S. Pub. 2004/0142025 A1 (the "'025 Publication"), WO 2005/007196, and US 2006/0134189 A1 — drops out as prior art.
• If any claim limitation is not supported by the 2002/2003 disclosure, the effective filing date moves forward and the AIA applies. Post-2004 material then becomes § 102(a)(1)/(a)(2) art with no grace period (the § 102(b)(1)(A) grace period would also be unavailable for the applicants' own 2004–2006 publications if the effective date is 2021).

The strategic significance is not hypothetical. In the Acuitas DJ contentions, the § 103 challenge to the '098 is pleaded over:

• MacLachlan et al., WO 2005/007196 (published Jan. 27, 2005);
• MacLachlan et al., U.S. Pub. 2006/0134189 A1 (published June 22, 2006);
• Lin et al., Three-Dimensional Imaging of Lipid Gene-Carriers…, 84 Biophys. J. 3307-16 (2003);
• Ahmad et al., New Multivalent Cationic Lipids…, 7 J. Gene Med. (2005).

Sources: https://www.bigmoleculewatch.com/wp-content/uploads/sites/2/2023/08/DNJ-3-23-cv-04200-1.pdf ; https://www.bigmoleculewatch.com/wp-content/uploads/sites/2/2024/05/SDNY-1-22-cv-02229-42.pdf ; https://pink.citeline.com/-/media/supporting-documents/pink-sheet/2022/03/acuitas-v-genevant-03-18-22.pdf

Every one of those four references post-dates June 28, 2002. There is no way to use them against the '098 unless Acuitas is contending the claims are not entitled to the 2002 priority date. The two candidate limitations for that attack are visible in the record itself:

1. "75% v/v to 100% v/v." The '098's own specification caps the disclosed alkanol range at 90% v/v ("about 45% v/v to about 90% v/v"; "about 65% v/v to about 90% v/v"; "most preferably about 80% v/v to about 90% v/v"). A claim range whose upper bound (100%) exceeds every disclosed embodiment invites both a § 112 written-description attack and a priority/§ 120 attack under In re Chu/PowerOasis line of authority (the claim as a whole must be supported by the parent).
2. "at different flow rates relative to each other." The '098 specification says only that the pump "can be configured to provide equivalent or different flow rates" — and then states the preferred practice: "lipid vesicles of well defined and reproducible mean diameters are prepared using substantially equal flow rates of the flow lines." Every worked example uses equal rates. The § 112 indefiniteness/written-description challenge to "flow rates" is already pleaded in Acuitas's counterclaims.

Analyst observation. The obviousness case against the '098 is therefore contingent, and the contingency is a priority/§ 112 dispute, not a § 103 dispute. This should be stated candidly: a § 103 challenge built on WO 2005/007196 presupposes that Acuitas wins the priority fight. Anyone briefing this patent should not present the two as independent.

1.2 Level of ordinary skill

A POSITA here would hold a Ph.D. (or M.S. plus experience) in chemistry, chemical engineering, biochemistry, pharmaceutics or a related discipline, with 2–3 years of hands-on experience formulating lipid vesicles and lipid–nucleic acid particles, including process development/scale-up of mixing operations. This is a crowded, mature, well-documented art with an unusually strong prior-art record.

2. The prior-art landscape

2.1 Art cited in the '098's own four corners

• U.S. Pat. No. 5,478,860 (Wheeler et al., Dec. 26, 1995) — microemulsion compositions for delivering hydrophobic compounds; expressly incorporated by reference in the '098.
• WO 01/05373 (Knopov et al., Jan. 18, 2001) — "techniques for preparing lipid vesicles using an ethanol injection-type process with a static mixer that provides a turbulent environment (e.g., Reynolds numbers >2000). Therapeutic agents may then be loaded after vesicle formation."
  This is the asterisked, examiner-flagged reference on the '098's front page (reproduced at https://storage.courtlistener.com/recap/gov.uscourts.njd.[510682](/patent/510682)/gov.uscourts.njd.510682.1.5.pdf). The '098 front page also lists WO 98/51278, WO 98/51285, WO 99/14346, WO 00/62813, WO 01/05374, WO 01/05873, WO 01/75164, WO 01/93836, WO 02/34236, WO 02/08541/085434, WO 02/087541, WO 03/059381, WO 03/097805, WO 2004/002453, WO 2004/065546, WO 2004/110499, WO 2005/007196, WO 2005/026372, WO 2005/120152 and WO 2015/011633.

Critical observation. The '098's own Background articulates the problem the invention supposedly solves: "Despite the apparent advances of U.S. Pat. No. 5,478,860 and WO05373, there exists a need for processes and apparatus for formulating and producing lipid vesicles, and in particular lipid vesicles encapsulating a therapeutic agent such as nucleic acid." That is a patentee admission that (i) both references are prior art, (ii) both are in the same field, and (iii) the outstanding problem was nucleic-acid encapsulation at scale. That paragraph is the single most useful sentence in the patent for a § 103 petitioner, because it supplies the motivation element directly from the patentee's mouth.

2.2 Pre-June-2002 art on ethanol-driven vesicle formation

• Batzri & Korn, Single bilayer liposomes prepared without sonication, Biochim. Biophys. Acta 298:1015-1019 (1973) — the seminal ethanol-injection disclosure: injecting an ethanolic phospholipid solution into an aqueous phase yields single-bilayer liposomes spontaneously, without sonication, and mild enough to avoid lipid degradation. https://pubmed.ncbi.nlm.nih.gov/[4738145](/patent/4738145)/
• Knopov WO 01/05373 — the continuous, automated version of the same idea.
• US 5,478,860 (Wheeler) — microemulsion/hydrophobic-drug delivery.

2.3 Pre-June-2002 art on coincident nucleic-acid encapsulation from an ethanol-containing solvent — the closest art

• Semple et al., Efficient encapsulation of antisense oligonucleotides in lipid vesicles using ionizable aminolipids: formation of novel small multilamellar vesicle structures, Biochim. Biophys. Acta 1510:152-166 (2001). Teaches: an ionizable aminolipid (DODAP); an ethanol-containing buffer system; up to 40% v/v ethanol; an acidic pH at which the aminolipid is cationic; a PEG-lipid required to prevent aggregation; encapsulation efficiencies up to 70%; particles 80–140 nm; and stable "SALP" on pH adjustment. DOI: 10.1016/S0005-2736(00)00343-6.
• Maurer et al., Spontaneous entrapment of polynucleotides upon electrostatic interaction with ethanol-destabilized cationic liposomes, Biophys. J. 80(5):2310-2326 (May 2001). Teaches entrapment of antisense oligonucleotides and plasmid DNA in 25–40% v/v ethanol, particles 70–120 nm, with "a direct correlation between the entrapment efficiency and the membrane-destabilizing effect of ethanol." https://pubmed.ncbi.nlm.nih.gov/[11325732](/patent/11325732)/
  Crucially, Maurer describes the Semple process in exactly the arrangement claim 1 recites: "addition of lipids dissolved in ethanol to an aqueous buffer solution containing antisense oligonucleotide resulted in the formation of small multilamellar liposomes trapping oligonucleotide between the lipid bilayers." That is "organic lipid solution" introduced into "aqueous solution including a nucleic acid."

Both references pre-date June 30, 2002 and therefore qualify as § 102(b) art even on the patentee's best priority case.

2.4 Art on the applicants' own process, available only if priority is lost

• U.S. Pub. 2004/0142025 A1 (the '025 Publication) — the published parent application. Its disclosure is materially the same specification as the '098: two reservoirs, a T-connector, flows meeting "as opposing flows at approximately 180°," and a pump "configured to provide equivalent or different flow rates."
• WO 2005/007196 and US 2006/0134189 A1 (MacLachlan) — later Arbutus publications of the same continuous-mixing platform.
• Lin et al. 2003 (84 Biophys. J. 3307) and Ahmad et al. 2005 — membrane-charge-density / lipid-DNA complex work, relevant mainly to the formulation dependent claims.
• US 9,005,654 (Protiva) Example 1 is itself documentary evidence that the '025 process became the "prior method" against which later Protiva work benchmarked itself.

Sources: https://www.bigmoleculewatch.com/wp-content/uploads/sites/2/2024/05/SDNY-1-22-cv-02229-42.pdf ; https://www.docketalarm.com/cases/Delaware_District_Court/1--22-cv-00336/Alnylam_Pharmaceuticals_Inc._v._Pfizer_Inc._et_al/docs/226/3.pdf

3. Grounds of rejection

Ground 1 (strongest available on pre-2002 art): Batzri & Korn + Semple 2001 + Knopov WO 01/05373

Motivation to combine (KSR v. Teleflex, 550 U.S. 398 (2007)):

1. Same field, same problem, express cross-recognition. Batzri & Korn, Semple, Maurer and Knopov all address lipid vesicle formation and entrapment; the '098 itself names Knopov and Wheeler as the state of the art it improves on.
2. The ethanol-destabilization mechanism supplies the medical/technical rationale. Maurer expressly links entrapment efficiency to ethanol-induced membrane destabilization; a POSITA would therefore increase control over the alkanol concentration at the moment of mixing — which is precisely what continuous, simultaneous pumping delivers.
3. Scale-up and GMP pressure. Knopov's stated objective is continuous, high-throughput, equipment-light manufacture. That is an articulated "design incentive" and "market force" (KSR) to move from batch injection to continuous two-stream mixing.
4. Elimination of downstream steps. Batzri & Korn and Semple both avoid sonication/extrusion; the '098 touts the same benefit. Combining them yields no more than the predictable sum of known advantages — the KSR "predictable results" rationale.
5. Routine optimization of result-effective variables. The claim's numeric hooks are exactly the kind of variables In re Aller / In re Boesch treat as obvious to optimize: alkanol concentration, mixing angle, and flow-rate ratio. The patentee's own Example 2 concedes that varying initial ethanol concentration "had little impact on either vesicle size or DNA encapsulation, providing that the ethanol concentration was high enough to ensure that none of the individual lipid components precipitated" — i.e., the claimed 75–100% window is defined by lipid solubility, a routine formulation constraint, not by an unexpected result.

Ground 2: Ground 1 in further view of US 5,478,860 (Wheeler) — supplies the lipid-formulation framework (amphipathic/cationic lipid, PEG-lipid, sterol, hydrophobic actives in the organic phase) and reinforces the "hydrophobic actives in solvent / hydrophilic actives in aqueous" split that the '098 recites as its own general teaching.

Ground 3 (contingent on priority loss): the applicants' own '025 Publication and WO 2005/007196

If the effective filing date moves past July 22, 2004, U.S. Pub. 2004/0142025 A1 becomes § 102(b) art as to the '098, and on its face discloses a first reservoir of aqueous nucleic acid solution, a second reservoir of ethanolic lipid solution, introduction into a T-connector as opposing flows at approximately 180°, and pumps configurable for equivalent or different flow rates — i.e., anticipation, with § 103 as the alternative. WO 2005/007196 / US 2006/0134189 A1 provide the second tier of § 103 art (same inventors, same platform, incremental disclosures of the process and its parameters). These are the references Acuitas actually pleaded, so this is the ground the parties appear to be litigating.

Ground 4 (claim 18 specifically)

Claim 18's 90°–180° range is a pure geometry modification of claim 1, and the '098's own specification supplies the case against it: "*The angle of mixing can also be changed, and lipid vesicles less than about 100 nm can be formed at angles of between about 27° and about 90° or even between 90° and 180°.*" A claim whose entire scope is a recitation of the patentee's own disclosed range of a design variable, with no criticality asserted, is the textbook In re Aller / KSR case. Claim 18 is, if anything, broader and weaker than claim 1.

Dependent claims

• Claim 2 (phospholipid / cholesterol / PEG-lipid / cationic lipid): Semple 2001 (DSPC + DODAP + PEG-ceramide + sterol) and Maurer 2001 (the same system) render the four-component architecture obvious. Motivation: PEG-lipid is taught to be required to prevent aggregation; the ionizable aminolipid is taught to be required for nucleic-acid association.
• Claim 8 (nucleic acid = RNA): Semple/Maurer expressly teach oligonucleotides (antisense); siRNA/snRNA/tRNA are recited as alternatives in the '098 and were well-known RNA species by 2002. No more than selection of a disclosed species.
• Exemplified molar ratios (20:45:10:25 DSPC:Chol:PEG-DSG:DODMA) and the "about 85% EE" targets: routine optimization of a known formulation, again with the patentee's Example 2 concession as an admission.

4. Patentee's best rebuttals, and how strong they are

5. Bottom line

(a) On pre-2002 art alone — Batzri & Korn (1973) + Semple 2001 + Maurer 2001 + Knopov WO 01/05373, optionally with US 5,478,860 — there is a defensible but not clean § 103 case against claims 1 and 18. Every substantive element is taught except the "opposing flows at about 180° … at different flow rates" recitation, which must be carried by design-choice / routine-optimization reasoning. Claim 18 (90°–180°) is the easier target; claim 1 (about 180°, different flow rates) is the harder one.

(b) The materially stronger case is the one Acuitas actually pleaded — WO 2005/007196 / US 2006/0134189 A1 / Lin 2003 / Ahmad 2005, and the applicants' own '025 Publication — but it is available only if the claims are denied the 2002/2003 priority date. The most plausible priority attack is on the unsupported upper end of the "75% v/v to 100% v/v" range (the specification caps at 90%) and/or on "different flow rates" (the specification's preferred mode is equal flow rates). If Acuitas prevails on that predicate, the '025 Publication arguably anticipates claim 1 outright.

(c) A POSITA would have been motivated to combine: the patentee's own Background supplies the articulated need (nucleic-acid-encapsulating vesicles at scale); Semple/Maurer supply the coincident-encapsulation mechanism and the claimed order of addition; Knopov supplies continuous two-stream processing; and the mixing geometry is a routine engineering variable that the patent itself describes as freely variable (27°–90° and 90°–180°).

6. Verification needed before relying on any of this

1. Obtain the '098's actual claim column from USPTO Patent Center / Patent Public Search or the issued PDF, to confirm the statutory category of claim 18 (the earlier section flagged that the filings are internally inconsistent on whether claim 18 is an apparatus or a process claim). An apparatus claim would change the § 103 analysis materially.
2. Obtain the '098's complete "References Cited" list and the examiner's reasons for allowance, to see whether WO 01/05373 was overcome on the "static mixer / turbulent flow" distinction — that would matter both ways.
3. Search for any IPR/JTI petition against the '098 (none surfaced in my searches, but I could not run an exhaustive PTAB query). Note that § 315(e) estoppel from Moderna's IPRs ran to the family's '069 and '435 patents, not the '098 (Fed. Cir. Dec. 1, 2021 — see the S.D.N.Y. transcript at https://storage.courtlistener.com/recap/gov.uscourts.ded.78146/gov.uscourts.ded.78146.71.0.pdf).
4. Verify the actual publication content of WO 2005/007196 and US 2006/0134189 A1 — I have only the citation, not the text.
5. Determine whether a pre-June-2002 reference discloses a T-connector/impinging-jet with opposed streams at differing flow rates — this is the weakest link in Ground 1 and the single highest-value search for a petitioner.

Companion authority worth citing: Arbutus Biopharma Corp. v. ModernaTX, Inc., No. 20-1183 (Fed. Cir. Apr. 11, 2023) (inherency; prior-art formulations plus a disclosed dilution method necessarily yielded the claimed morphology) — https://www.jdsupra.com/post/contentViewerEmbed.aspx?fid=aa811825-b8b7-4946-af14-745d5bba419e — and KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007).