US 5118528

I'll search for authoritative information on this patent number and check for any 2026 CAFC activity.

Let me check specifically for any 2026 CAFC activity involving this patent or its family.

US 5,118,528 — Analyst Summary

Important framing note: The full patent text supplied in this session is the authoritative source here, and I've cross-checked it against Google Patents and uspto.report. All identifiers are reproduced exactly as they appear; I have not corrected anything.

Bibliographic data

Term/expiry note: the official front-page notice states that "the portion of the term of this patent subsequent to September 17, 2008 has been disclaimed" (a terminal disclaimer, consistent with the earlier-issued sibling patent US 5,049,322). Google Patents separately lists an "anticipated expiration" of 2009-06-02, which appears to be a mechanical 17-years-from-issue calculation and does not account for the terminal disclaimer. I could not independently verify the operative expiry date from a primary USPTO record in this session — treat the September 17, 2008 disclaimed date as the more likely effective end of term, with the caveat that this is unconfirmed.

Abstract (as granted)

The process comprises: (1) preparing a liquid phase consisting essentially of a solution of the substance in a solvent or mixture of solvents, optionally with one or more surfactants; (2) preparing a second liquid phase consisting essentially of a non-solvent or mixture of non-solvents for the substance, optionally with surfactants, the non-solvent being miscible in all proportions with the solvent; (3) adding one liquid phase to the other with moderate stirring to produce a colloidal suspension of nanoparticles of the substance; and (4) if desired, removing all or part of the solvent(s) and non-solvent(s) to give a colloidal suspension of the desired concentration or a nanoparticle powder. Particles are sub-500 nm, spherical, matrix-type. Particle formation in step (3) is "practically instantaneous," producing a milky-white suspension showing the Tyndall effect.

Plain-language overview of the independent claims

Claim 1 — Composite (polymer + drug) nanoparticles.
Two liquids are brought together:

• Liquid 1: a solution containing both a film-forming material and a biologically active substance, dissolved in a solvent (or solvent mixture); surfactants optional.
• Liquid 2: a greater volume of a non-solvent (or non-solvent mixture) for that film-forming material and biologically active substance; surfactants optional. The non-solvent must be miscible in all proportions with the solvent.

Mixing them causes substantially instantaneous precipitation of composite particles (film-forming material + active substance), yielding a colloidal suspension of composite nanoparticles under 500 nm. In everyday terms: dissolve a polymer and a drug together in a water-miscible organic solvent, then pour that into a larger volume of water (or another non-solvent) — the polymer and drug co-precipitate on contact as nanospheres. This is the classic "nanoprecipitation"/solvent-displacement concept, and claim 1 is the version that requires a co-dissolved active ingredient.

Claim 15 — Polymer-only nanoparticles.
The same two-phase combine-and-precipitate step, but the first phase is simply a solution of a polymer (no biologically active substance required), and the second phase is a greater volume of a non-solvent (mixture) for that polymer, miscible in all proportions with the solvent. Mixing substantially instantaneously precipitates polymer nanoparticles (<500 nm) as a colloidal suspension. Claim 16 depends from claim 15 and specifies that the polymer is polylactic acid.

Both independents are product-by-process-flavoured: the operative step is the act of combining, and the claim recites the resulting colloidal nanoparticle suspension as the output.

Dependent claims (summary): 2 — remove solvent/non-solvent to concentrate the suspension or obtain a powder; 3 — removal by lyophilization; 4 — add phase (1) to phase (2); 5 — a lesser amount of non-solvent than solvent is used; 6 — 0.1–10 wt% surfactant in the suspension; 7 — 0.2–2 wt% surfactant; 8 — film-forming material is a polymer; 9 — polymer at 0.1–10 wt% in phase (1); 10 — polymer at 0.2–2 wt%; 11 — a second substance bound to the nanoparticles; 12 — that second substance is biologically active; 13 — the biologically active substance is a fatty substance; 14 — nanoparticle diameter about 200 nm.

Literal-reading flag (no correction applied): claim 1 requires "a greater volume of a second liquid phase," while dependent claim 5 recites "a lesser amount of non-solvent … than solvent." As reproduced in the available text, these two limitations point in opposite directions. I am reporting the claim text as it appears rather than reconciling it; the discrepancy could be an artifact of the text source, and I have not verified claim 5 against the USPTO printed copy.

Litigation / CAFC 2026 check — negative result

I searched for CAFC 2026 dockets, Federal Circuit appeals, and district-court actions involving US 5,118,528 (and the literal string "5,118,528" / "5118528"):

• No 2026 CAFC docket, appeal, or opinion involving US 5,118,528 was found. The 2026 Federal Circuit and UPC materials that surfaced were unrelated matters (e.g., Wyeth v. AstraZeneca EGFR-enablement appeal; Guardant Health v. University of Washington, CAFC No. 2024-1129; UPC Ericsson/Transsion and SharkNinja/SEB proceedings).
• The Google Patents family record (Family ID 9342497) does carry a "Family has litigation / First worldwide family litigation filed" flag linking to Darts-ip, indicating the family has been litigated somewhere historically — but the link does not identify parties, forum, or dates, and no US appellate activity tied to this patent in 2026 is documented.
• This outcome is consistent with the patent's long-expired status; absent a live dispute over past damages, a 2026 CAFC appeal concerning the '528 patent would be unusual.

Confidence level: I have high confidence in the bibliographic and full-text data above (drawn from the patent document itself plus uspto.report). I have low/uncertain confidence regarding (a) the exact operative expiration date and (b) the existence and identity of any family litigation, because the Darts-ip payload was not retrievable in this session.

Source discrepancies worth noting (identifiers left uncorrected)

• A Mendeley catalogue entry attributes the title "Process for the preparation of dispersible colloidal systems of a substance in the form of nanoparticles" to U.S. Patent 5,049,322 (1991) with an abstract describing a protein heat-coagulation process, yet links to freepatentsonline.com/5118528 for US 5,118,528. These are two different patents in the same CNRS family (the protein-based process vs. the polymer/drug nanoprecipitation process), and the secondary source appears to conflate them.
• uspto.report renders the grant date as "June 2, 1"; the verified date is June 2, 1992.
• Cited prior art of record (7 references): CH 201942; DE 738604; AU 495261; US 3,691,090 (Kitajima/Fuji Photo); US 4,585,651 (Beck/Stolle); US 4,492,720 (Mosier); WO 86/03676 (Ohio State University Research Foundation).
• Family members across jurisdictions: EP0275796B2, JP2739896B2, CA1292168C, ATE74024T1, DE3777796D1, ES2031151T5, FR2608988B1, GR3004152T3, GR3018122T3.

Sources: https://patents.google.com/patent/US5118528/en ; https://uspto.report/patent/grant/5118528 ; https://www.mendeley.com/catalogue/c3e40888-0bd9-3f6a-9151-cbe39711debe/

I'll research litigation involving US Patent 5,118,528. Let me run several targeted searches.

Let me search more specifically for litigation records tied to this exact patent.

Bottom line

I could not identify any U.S. litigation asserting or otherwise involving U.S. Patent No. 5,118,528 (the Fessi et al. "nanoprecipitation" patent) as an issued U.S. patent in the sources I was able to search. I am not aware of a confirmed infringement suit, declaratory-judgment action, or PTAB proceeding naming this patent, and I did not find one in the searches performed. I am therefore reporting "no U.S. litigation identified," with the important caveat below about a family-level litigation flag.

I want to be explicit that this is a negative finding on limited research, not a certification that no case ever existed.

Patent identification (to avoid conflation)

Because the U.S. patent expired on or about June 2, 2009, it could not be asserted in any suit filed after that date. Any U.S. litigation would necessarily predate 2009.

What I did and did not find

Searching for the exact number "5,118,528" / "5118528" in litigation-oriented sources returned only false positives for different patents that share the colloquial shorthand "'528 patent":

• ParkerVision, Inc. v. Apple Inc. and Qualcomm Inc., No. 3:15-cv-01477 (M.D. Fla.) — asserted U.S. Patent No. 9,118,528 (radio-frequency down-conversion), a different patent entirely.
• Otsuka Pharmaceutical Co. v. Teva, Apotex, Sandoz, Zydus, et al. (D.N.J.) — the '"528 patent" there is Otsuka's aripiprazole patent, again unrelated.
• Resh v. various defendants, No. 5:22-cv-01427-EJD (N.D. Cal.) — unrelated pool-pole patents.
• Various IPR/CBM materials citing "RE43,528," U.S. 8,528,118, etc. — all unrelated numbers.

None of these involve CNRS, Fessi, or nanoparticle/nanoprecipitation technology, and none is U.S. 5,118,528.

The one relevant flag — family-level, not case-level

The Google Patents record for US 5,118,528 carries a "Family has litigation / First worldwide family litigation filed" indicator, sourced from Darts-IP, keyed to family ID 9342497:

• https://patents.darts-ip.com/?family=9342497 (linked from https://patents.google.com/patent/US5118528/en)

This tells us that Darts-IP has recorded at least one litigation somewhere in the world touching this patent family (the family includes EP 0275796 B2, FR 2608988 B1, JP 2739896 B2, and CA 1292168 C). It does not, on the public Google Patents page, disclose the parties, court, case number, or date. I was unable to retrieve the underlying Darts-IP case record (it is a subscription database), so I cannot responsibly supply plaintiff, defendant, jurisdiction, case number, or outcome. Given the "worldwide family" framing and the French origin of the invention, that proceeding may well be a European or French action on EP 0275796/FR 2608988 rather than a U.S. case on the '528 patent — but that is an inference, not a finding.

Recommended verification steps (authoritative, to close the gap)

1. PACER / CourtListener RECAP — full-text search the docket databases for "5,118,528" and for "Fessi" / "Centre National de la Recherche Scientifique" as patent plaintiff, restricting to pre-2010 filings.
2. Darts-IP (family 9342497) — retrieve the specific case record behind the flag; this is the most likely single source that answers the question definitively.
3. Unified Patents litigation portal (portal.unifiedpatents.com/litigation) and Lex Machina / Docket Navigator — patent-number search.
4. USPTO Patent Trial and Appeal Board (IPR/PGR/CBM) — confirm no AIA proceeding (none would be possible here given the 1992 grant, but confirm).
5. EPO opposition/appeal records for EP 0275796 B2 — the "B2" designation indicates the European patent survived opposition in amended form, which often accompanies litigation; this is worth checking directly via the EPO Register and Global Dossier.

If you want, I can run those targeted searches once the tool budget resets and report back with case-level detail.

I'll start by checking the structured data (ODP: no AIA proceedings) against live sources, since PTAB activity can predate or postdate the ODP ingest.

No hits on the first pass. Let me confirm with targeted searches for proceedings, reexams, and litigation — including the Darts-IP "family has litigation" flag.

Let me check for any reexamination (the pre-AIA route) and for the flagged family litigation, plus a final sweep of PTAB dockets.

Proceedings overview

Total AIA trial proceedings on file: 0. The structured "PTAB proceedings on file" block (USPTO Open Data Portal, current ingest) returns no IPR, PGR, or CBM — so the breakdown is 0 active / 0 claims-invalidated / 0 claims-sustained / 0 settled / 0 institution-denied. My live searches (Google Patents' citation and "Cited By" tables in the authoritative text, plus third-party PTAB docket sweeps) likewise surfaced no AIA trial number referencing US 5,118,528. The bottom-line defensive posture is not "hardened by IPR"; it is "the patent is dead by operation of law — check the expiration date before you spend a dollar on prior art." This is a 1986-priority patent that issued 1992-06-02 and reached anticipated expiration on 2009-06-02 — roughly three years before the first IPR was even filable (AIA trials became available 2012-09-16).

No proceedings exist — and the reason matters

There is no ### {PROCEEDING_NUMBER} entry to write because the canonical list is empty and no secondary source contradicts it. Rather than dress up a nonexistent IPR, here is the honest structural explanation for the absence:

• IPR/PGR were unavailable for most of this patent's life. The Leahy–Smith America Invents Act created these proceedings effective 2012-09-16. US 5,118,528 expired 2009-06-02. An IPR can technically be filed against an already-expired patent (to obtain a clean invalidity ruling for past damages), but it is rare and economically pointless unless the patent is being asserted for back damages — and no such IPR exists here.
• PGR is categorically unavailable. Post-Grant Review applies only to patents with an effective filing date on or after 2013-03-16. This patent's priority date is 1986-12-31. It can never be a PGR candidate.
• CBM is inapplicable. Covered Business Method review (2012-09-16 through 2020-09-16) covered only patents claiming a "financial product or service." US 5,118,528 claims a solvent/non-solvent nanoparticle nanoprecipitation process (claims 1 and 15 are the independents; claim 1 recites a film-forming material + biologically active substance, claim 15 a polymer). Nothing financial about it — it was never CBM-eligible.

Litigation flag — unresolved

The Google Patents record carries a "Family has litigation" / "First worldwide family litigation filed" banner pointing to Darts-IP family ID 9342497 (https://patents.darts-ip.com/?family=9342497). That is a worldwide family litigation indicator tied to the FR 2608988 / EP 0275796 family, not a US PTAB matter. I could not verify the specifics of that litigation from the sources retrievable in this session, and I will not guess at parties, venues, or docket numbers. Treat the existence and details of any US infringement action on US 5,118,528 as unverified. Note also the prosecution-family cousins, which are separate patents and not proceedings on this patent: US 5,049,322 (Fessi et al., protein/thermal variant) and US 5,133,908, with the CNRS protein counterpart EP 0349428B1.

Strategic summary

Claim status. Because no claim-level adjudication (IPR FWD, CBM, or court judgment of invalidity) exists in the record, all 16 claims — independents 1 and 15, and dependents 2–14 and 16 — are "UNTESTED" by the PTAB, not "sustained." None were canceled; none were confirmed by the Board. The claim set as issued stands unchanged: claim 1 (film-forming material + biologically active substance, precipitated into composite nanoparticles < 500 nm), claim 15 (polymer variant), and claim 16 (polylactic acid). Before anyone builds a defense strategy on the claims, they should first confirm the term: Google's record shows "Anticipated expiration 2009-06-02" and legal status "Expired – Lifetime." An expired patent cannot be infringed prospectively (35 U.S.C. § 271(a) is present/future-tense; recovery, if any, is limited to the six-year lookback under § 286 for past damages). The first question for any defendant is therefore "when did the accused acts occur?" — not "what art do we have?"

Estoppel landscape. There is no § 315(e)(2) estoppel to speak of, because no petitioner ever reached a final written decision on this patent. Every prior-art ground that exists — the classic references the applicant itself cited (CH 201942, DE 738604, US 3,691,090 to Fuji Photo, US 4,492,720 to Mosier, WO 1986/003676 to Ohio State) plus the abundant post-1986 nanoprecipitation literature (Fessi et al., Int. J. Pharm. 55, R1–R4 (1989)) — is theoretically unencumbered. But this cuts both ways: modern IPR art on an expired patent is really about back damages, and threshold validity challenges to a 1986-priority, 1992-issue patent (e.g., § 112 written-description/enablement of the < 500 nm range, or § 103 over the solvent-displacement art) would be litigated in district court, not the PTAB, unless and until the patent is asserted for back royalties.

Pattern signals. No petitioner has filed against this patent at all — no repeat-petitioner pattern, no defensive aggregator (Unified Patents or similar) in the chain, and no PTAB-to-CAFC appeal history, because there was never a proceeding to appeal. The Darts-IP "family litigation" flag is the only adversarial signal, and it is a family-level (largely European) marker rather than a US PTAB record. If you see a demand letter citing US 5,118,528, the burden-shifting asymmetry you'd normally exploit — patent owner winning at the Board, or losing there — simply does not exist here.

Recommended next steps

• Lead with expiration, not invalidity. US 5,118,528 is expired (2009-06-02). Confirm this against the USPTO Patent Center maintenance-fee and expiration records for US 5,118,528 before engaging on the merits. If a purported assertion seeks prospective relief or a license covering post-2009 activity, it is facially defective.
• There is no IPR FWD to link to, and I will not link to one that does not exist. The best available public primary source remains the patent itself: https://patents.google.com/patent/US5118528/en. For any European family activity, the counterpart is EP 0275796B2.
• If past damages are in play, the analysis shifts to § 286's six-year window and to § 282 defenses in district court — § 112 for the breadth of the "less than 500 nm" limitation and § 103 over the 1980s solvent-displacement/nanoprecipitation literature (Fessi 1989; the Marsh/emulsification-evaporation art discussed in the patent's own Background). No estoppel bars these; nothing was ever litigated to judgment.
• Verify the Darts-IP litigation flag directly (the family link requires a Darts-IP subscription) and pull the FR/EP case history before relying on it. I could not confirm its contents, so I am flagging it as an open item rather than asserting a fact.
• If you were expecting a PTAB record, its total absence is itself the signal: well-asserted, live patents of this prominence almost always attract IPRs. The absence here is fully explained by the calendar — the patent died before AIA trials were created — not by any defensive victory.

Limitations: this conclusion rests on (a) the ODP structured block (no proceedings) and (b) web searches that returned no PTAB docket hits. Web-search recall on numeric patent identifiers is imperfect, so this is a high-confidence but not infallible "zero." If you have a specific PTAB proceeding number in hand, supply it and I will pull the institution decision and FWD directly.

I'll research the assignment record for US 5118528 from the USPTO Assignment Center and cross-reference sources.

Let me try to reach the Assignment Center records and cross-reference litigation.

Let me verify via assignment mirrors and check the family litigation flag.

Research limitations (read first)

I was unable to pull live records from the USPTO Assignment Center (assignmentcenter.uspto.gov / assignment.uspto.gov) — that database is a session-driven, non-indexed application, and my search layer returned no reel/frame data for this patent. What follows is grounded in (a) the authoritative Google Patents family/legal-events text for US 5,118,528 and (b) secondary literature, not in Assignment Center reel/frame entries. I state plainly wherever a fact is unverified rather than inferring it.

Critically, the Google Patents legal-events block for US 5,118,528 contains no assignment (AS) events at all — only filing, grant, publication, and expiration. That is itself the central finding.

Inventors

Sources: Google Patents "Inventor" field for US 5,118,528; EPO family member labelling ("FESSI CURT [FR]); academic literature.

Notes and caution:

• Literal reading required: the patent and EPO records render the first inventor as "Curt Fessi". The scientific literature universally cites him as "H. Fessi" (Hatem Fessi). I am flagging the discrepancy rather than auto-correcting the patent record.
• A US academic (Thies) is co-invented with three French academics, consistent with a visiting-scientist arrangement at the CNRS/Paris-Sud laboratory. I could not verify Thies's exact institutional status at the 1986 priority date.
• Unusual patterns: none detectable. I found no evidence of inventors departing the original assignee, and no evidence of inventor-held rights being separately assigned. No fire-sale precursor.

Original assignee

• Entity on the issued patent: Centre National de la Recherche Scientifique (CNRS) — listed as both Original Assignee and Current Assignee in the fetched patent record.
• Primary line of business: France's largest publicly funded basic-research organisation (government research agency; ~1,000 laboratories). It is a research institution, not a manufacturing company.
• Product embodying the claims: No. CNRS does not commercialise products; it licenses technology. The "nanoprecipitation" process claimed here (claim 1 composite particles; claim 15/16 polymer particles, incl. polylactic acid) was widely adopted downstream by pharma, but CNRS shipped none of it.
• Current status: Operating (still an active French public research body as of 2026). No bankruptcy, no acquisition, no dissolution surfaced.

Assignment timeline

I could not retrieve any recorded assignment entries for US 5,118,528. The Google Patents legal-events record for this patent lists only:

• 1990-10-04 — application filed (continuation of Ser. No. 07/140,245, filed 1987-12-31)
• 1992-06-02 — application granted / publication of US5118528A
• 2009-06-02 — anticipated expiration

There is no post-issuance assignment, security agreement, merger, change-of-name, license, or release event reflected in that record. No correspondent of record can be reported, because no recordation was identified. No reel/frame numbers exist to cite, and I will not invent them.

If an Assignment Center record does exist, it would in all likelihood be only the initial inventor→CNRS assignment executed around the 1987 filing — but I could not verify even that, so it is not reported as a finding.

Corollary: with no transfer on the record, the chain terminates at CNRS, the original assignee.

Timeline diagram

No assignment events exist to stack; the diagram therefore shows only the bare ownership-relevant milestones.

timeline
    title Ownership of US 5118528
    1986 : French priority application filed
    1987 : US application filed
    1990 : Continuation application filed
    1992 : Patent issued to CNRS
    2009 : Patent expired

NPE / troll-pattern signals

1. Shell-entity transfer — not present. No transfer at all is on record; the assignee remains CNRS, a government research agency, not a "IP / Holdings / Ventures" LLC. No registered-agent address, no single-member LLC. (Evidence: Google Patents legal-events block for US 5,118,528 shows no assignment; "Current Assignee = CNRS.")

2. Known asserter in the chain — not present. CNRS does not appear on the enumerated lists (Acacia, Marathon, IV, IPNav, Wi-LAN, Mosaid/Conversant, Vringo, Pendrell, Innovatio, MPHJ, Lumen View, Round Rock, DGC, Spangenberg entities). Research institutions sometimes enforce patents, but that is not the same finding — and there is no evidence of any such chain here.

3. Repeat correspondent across the chain — unclear / not assessable. No reel/frame records were retrievable, so no correspondent name or firm of record can be cited. I expressly decline to infer one.

4. Cascading transfers — not present. Zero consecutive assignments; nothing through chained LLCs.

5. Pre-litigation transfer — not present. No assignment exists to be dated relative to a suit; no US infringement suit naming this patent was identified.

6. Bankruptcy fire-sale — not present. CNRS is a solvent public body; no Chapter 7/11 event.

7. Privateering — not present / unclear. No evidence of CNRS transferring the patent to an NPE to assert on its behalf. Note the Google Patents page carries a "Family has litigation — First worldwide family litigation filed" flag (Darts-ip family ID 9342497) covering the FR/EP/JP/CA/US family (FR2608988B1, EP0275796B2, JP2739896B2, CA1292168C). I could not resolve which member/case that flag references, and it does not, on its own, evidence any ownership transfer or privateering. Treat as unresolved.

8. Defensive aggregator (anti-NPE) — not present. The chain does not terminate at RPX, AST, LOT, Unified Patents, or OIN. It terminates at the original assignee. Separately, the patent is expired since 2009-06-02, which functionally neutralises it — but that is expiry, not defensive aggregation.

Verdict

Insufficient data (no assignment records retrieved; only the original assignee is evidenced).

The record shows no post-issuance assignment whatsoever — the Google Patents legal-events block for US 5,118,528 contains only filing (1990-10-04), grant/publication (1992-06-02), and anticipated expiration (2009-06-02), and the patent's own "Current Assignee" and "Original Assignee" fields both read Centre National de la Recherche Scientifique (CNRS). With no transfer chain, there is no shell entity, no repeat correspondent, no cascading LLCs, and no assertor to evaluate; the patent also expired on 2009-06-02, so no live assertion is possible. Verdict falls to Insufficient data rather than any affirmative NPE call, and I found no evidence supporting an NPE classification.

Verification links:

• USPTO Assignment Center (search by patent number 5118528): https://assignmentcenter.uspto.gov/
• Legacy Assignment Search: https://assignment.uspto.gov/patent/index.html
• Google Patents legal events for this patent: https://patents.google.com/patent/US5118528/en (see "Legal Events" / "Worldwide applications" — no assignment entries)

Caveat for the file: because I could not query the Assignment Center directly, a confirmatory manual lookup by patent number is required before this "no transfers on record" conclusion is treated as final. If a single inventor→CNRS assignment (circa 1987) surfaces there, it changes nothing about the verdict.

I'll research this systematically — first confirming the target patent, then each cited reference.

Now let me research the remaining cited references.

Prior-Art Analysis — US 5,118,528 A

Note on sources: The authoritative full text you supplied (fetched from https://patents.google.com/patent/US5118528/en on 2026-09-30) was treated as ground truth, including its "Patent Citations (7)" table, its "Family Cites Families (1)" table, and its claim set. Live searches were run to characterize the cited references; four of them could not be fully retrieved before the search-step limit was reached, and those conclusions are expressly flagged as provisional. Patent numbers and identifiers are reproduced literally as they appear.

1. The target patent

Critical date for §102 purposes: 1986-12-31 (FR priority). Every reference below must pre-date that to be §102 art.

Claim architecture (16 claims). Independent claims are 1 (film-forming material + biologically active substance) and 15 (polymer only). Claim 1 requires: (a) a solution of both a film-forming material and a biologically active substance in a solvent; (b) a greater volume of a second phase that is a non-solvent miscible in all proportions with the solvent; (c) substantially instantaneous precipitation of composite particles; (d) colloidal nanoparticles < 500 nm, spherical, matrix type. Claim 15 is the same schema with a polymer alone. Claims 2 (solvent removal), 3 (lyophilization), 4 (order of addition), 5–7 (non-solvent/surfactant proportions), 8–10 (polymer and its concentration), 11–12 (second substance bound to the nanoparticles), 13 (fatty-substance active), 14 (~200 nm), 16 (polylactic acid) are all dependent.

Analyst observation: claim 5 (lesser amount of non-solvent than solvent) appears internally inconsistent with claim 1's "a greater volume of a second liquid phase." That is a claim-drafting defect worth noting, but it does not affect the prior-art mapping below.

2. The seven cited references, mapped to the claims

2.1 CH 201,942 A — the "brine/suspension of organic substances" process

• Full citation: CH 201942 A, Georg Krause (A Dr Krause Georg), "Process for the production of brines respectively. Suspensions of organic substances." Priority/listed date 1935-07-08; publication 1938-12-31. Source: https://patents.google.com/patent/CH201942A/en
• Disclosure (verified from the German text): teaches introducing "echte, mit organischen Lösungsmitteln hergestellte Lösungen im wesentlichen nicht wasserlöslicher organischer Substanzen in wäßrige Medien, insbesondere Wasser" — true organic-solvent solutions of substantially water-insoluble organic substances — into aqueous media, and forming the sols/suspensions "unter Verwendung von kolloiden, grenzflächenaktiven Zusatzstoffen" (using colloidal, surface-active additives), so as to give particles "wahlbare, bleibende Formen," including "isotrope, kugelige oder anisotrope Teilchen" (isotropic spherical or anisotropic particles).
• §102 assessment: This is a direct conceptual ancestor of the solvent-shifting/nanoprecipitation concept — organic solution in, water out, surfactant present, spherical particles obtainable. However, it does not disclose (i) a specific particle size below 500 nm, (ii) a film-forming material in combination with a biologically active substance, or (iii) a matrix-type spherical particle as a limitation. It therefore does not appear to anticipate any single claim as a whole.
  • Candidate dependent-claim exposure: at most claim 4 (adding the organic phase to the aqueous phase), and only if claim 1 were first found anticipated; and claim 6/7 (surfactant) if the "grenzflächenaktive Zusatzstoffe" are equated with the claimed surfactant.
  • Best role: §103 art, and §102 art against the pre-characterization disclosure of the process. Very strong "teaching" evidence that the solvent/non-solvent precipitation concept was long known.

2.2 DE 738,604 C — Degkwitz hydrosols (the closest process reference)

• Full citation: DE 738604 C, Rudolf Degkwitz, "Process for the production of hydrosols with a selectable shape and size of the colloidal particles." Priority 1935-07-09; published 1943-08-23. Source: https://patents.google.com/patent/DE738604C/en
• Disclosure (verified from the German text): dissolving sparingly/insoluble, solid, crystallizable organic substances in water-miscible organic solvents, then "die Lösungen in Wasser oder wäßrige Medien in Gegenwart solcher grenzflächenaktiver Stoffe einträgt" (introducing those solutions into water or aqueous media in the presence of surface-active substances), holding temperatures below the melting point of the smallest particles, and then "das Sol unter Vertreibung des organischen Lösungsmittels auf die gewünschte Konzentration eingedampft" (evaporating off the organic solvent to concentrate the sol to the desired concentration). A second embodiment introduces the solution at temperatures above the melting point of the largest particles and stabilizes with protective colloids such as proteins or carbohydrates, then evaporates the organic solvent. European search reports characterize this document as the archetype of the "precipitation into an anti-solvent" family.
• §102 assessment — element-by-element against claim 1:
  • Solvent phase (organic solvent) — disclosed.
  • Non-solvent phase (water/aqueous), miscible with the solvent — disclosed.
  • Surface-active additive — disclosed.
  • Removal of the organic solvent/concentration step — disclosed (mapping to claim 2, at least the concentration half).
  • Spherical (isodiametric) particles of selectable size — disclosed as one embodiment.
  • Missing: an express "less than 500 nm" limitation. The document claims colloidal particles of selectable size; a hydrosol is by definition sub-micron, and "wählbarer Größe" is arguably broad enough to read on <500 nm, but there is no express or exemplary teaching of that numerical limit.
  • Missing: the combination of a film-forming material and a biologically active substance as the precipitated solute. DE '604 addresses a single "Solbildner," with proteins/carbohydrates appearing only as protective colloids, not as a co-precipitated active agent.
• Conclusion: DE 738,604 C is the most relevant prior art to the '528 patent's process concept and the strongest §103 combination anchor. Under §102 it does not appear to anticipate independent claim 1 or 15 as a whole (missing the <500 nm and two-substance/active-agent limitations), and it only anticipates a dependent claim such as 4 if claim 1 is otherwise met. It is nonetheless the single most damaging reference in the list.

2.3 AU 495,261 A — transformer noise reduction

• Full citation: AU 495261 A, Mcgraw-Edison Company, "Noise reducing means for transformers." Priority 1961-05-23; publication 1963-05-02.
• Disclosure: electrical-transformer noise abatement. Not verified in full text (search returned no substantive record for this document).
• §102 assessment: No §102 relevance to any of claims 1–16. On its face this is non-analogous art — it is not from the fields of colloid chemistry, polymer precipitation, micro/nanoencapsulation, or pharmaceuticals, and could not have been reasonably expected to bear on the problem of forming sub-500 nm matrix particles. It should not be relied on for anticipation or for an obviousness combination. Its presence in the citation list looks like a formality/ID-citation artifact; I could not confirm which party cited it because the supplied citation table does not carry the per-row "* cited by examiner / † cited by third party" flags.

2.4 US 3,691,090 A — Fuji Photo Film "Encapsulation method"

• Full citation: US 3,691,090 A, Kitajima Masao; Yamaguchi Tsutomu; Kondo Asaji; Muroya Noriyuki, assignors to Fuji Photo Film Co., Ltd., "Encapsulation method." Priority 1969-01-16; application filed 1970-01-13; granted 1972-09-12. Source: https://patents.google.com/patent/US3691090
• Disclosure (verified): dispersing a core material in a solution of an encapsulating material in an organic solvent; adding that dispersion to an aqueous inorganic salt solution in which it is suspended as oily drops; then evaporating the organic solvent. Preferred encapsulating materials include ethyl cellulose, cellulose acetate phthalate, polyacrylic acid, polymethacrylic acid, maleic anhydride copolymers, shellac. Solvents: lower alcohols, acetone/MEK, dioxane/THF, esters, hydrocarbons. Salts: NaCl, KCl, NH₄Cl, etc. The patent states expressly that the organic solvent is "miscible with water and causes phase separation when mixed with an aqueous inorganic salt solution."
• §102 assessment: The reference is a classic emulsification/phase-separation–solvent-evaporation process. Critically, the aqueous phase is designed not to be miscible in the operative sense — the salt solution induces phase separation and the droplets must "maintain their shape during evaporating the organic solvent." The claim 1/15 element "miscible in all proportions with the solvent" is therefore absent and, indeed, contradicted. Additionally, the product is a capsule (a distinguishable core within a capsule wall), not a matrix-type particle, and no <500 nm size is disclosed.
  • Conclusion: no anticipation of independent claims 1 or 15. It is good §103 art for step (2)/(4) concepts (solvent evaporation to recover particles), and it discloses several of the polymers recited in the '528 specification (cellulose acetate phthalate, acrylic polymers). It has no independent §102 bite.

2.5 US 4,492,720 A — Mosier microspheres

• Full citation: US 4,492,720 A, Benjamin Mosier (Houston, TX), "Method of preparing microspheres for intravascular delivery." Application 06/552,160, filed 1983-11-15; granted 1985-01-08. Family member EP 0142085 B1. Sources: https://patents.google.com/patent/US4492720 ; https://uspto.report/patent/grant/[4492720](/patent/4492720) ; http://data.epo.org/gpi/EP0142085B1
• Disclosure (verified, including claims): dissolving a therapeutic or diagnostic agent and a non-toxic matrix material in a first organic solvent of high dielectric constant (above 15, preferably 20–40 — lower alcohols, acetone, dioxane, THF, acetonitrile); dispersing that solution in a second, immiscible organic solvent of low dielectric constant (<5 — petroleum ether, hexane, heptane) present in at least as great a volume; forming an emulsion; then removing both solvents while keeping droplets below the congealing temperature of the matrix material; recovering solid microspheres. Matrix materials expressly include fatty acid mono-, di- and tri-glycerides (C12–C22), propylene glycol monoesters, fatty acids, waxes, cellulose derivatives, gelatin-type materials, and — Example IV — poly-d,l-lactide. Active agents include doxorubicin (Adriamycin), floxuridine, methotrexate, etc. Recovered microspheres: 50–350 µm claimed; examples span 1–25 µm and 1–10 µm (Example VII).
• §102 assessment: This reference anticipates the concept of dissolving a drug together with a matrix polymer/lipid in a common organic solvent and recovering matrix particles — highly material to claims 8, 13 and 16 — but it is not anticipatory of independent claims 1 or 15 because:
  • the second solvent is expressly immiscible with the first (dielectric-constant split), so the "miscible in all proportions" element is absent;
  • particle size is in the micron range (50–350 µm claimed), not <500 nm; no nano-scale teaching appears;
  • precipitation is by the congealing/cooling of a heat-liquifiable matrix during solvent removal, not "substantially instantaneously" on combining the phases.
  • §102 candidate set: none of claims 1–16 as a whole; strongest argument at most for the substrate limitations within claims 8, 13, 16, which are dependent claims that additionally require all elements of claim 1 or 15.

2.6 US 4,585,651 A — Stolle, immunization

• Full citation: US 4,585,651 A, Stolle Research & Development Corporation, "Active/passive immunization of the internal female reproductive organs." Priority 1978-10-17; granted 1986-04-29.
• Disclosure: Not verified. The title and the 1986 grant date place it in the antigen/microsphere-delivery field (Stolle's known work concerns microencapsulated antigens delivered locally to reproductive tissue). It is a pre-priority-date (1986-12-31) document.
• §102 assessment (provisional): On the title alone, this is at most background art showing administration of a biologically active substance in a polymer/lipid matrix. It is unlikely to disclose a solvent/non-solvent miscible-pair precipitation process or a <500 nm product, and therefore unlikely to anticipate any claim. Confirm the full text before relying on this negative conclusion.

2.7 WO 1986/003676 A1 — Ohio State "Small particle formation and encapsulation"

• Full citation: WO 1986/003676 A1, The Ohio State University Research Foundation, "Small particle formation and encapsulation." Priority 1984-12-21; published 1986-07-03.
• Disclosure: Not verified (retrieval not completed within search limits). The title is directly on-point: small particle formation coupled with encapsulation.
• §102 assessment (provisional — flag as the highest-priority reference to pull): If this PCT application discloses forming sub-micron/matrix particles by precipitating a dissolved polymer or organic substance upon admixture with a miscible non-solvent, it is a candidate anticipatory reference for claims 15–16 (and possibly 1). Its 1984-12-21 priority date places it squarely before the '528 priority date. This document must be obtained and read in full before any validity conclusion is drawn. Note it is distinct from the '528 family — do not conflate it with the '528 assignee's own relatives.

3. The family-level citation you should not overlook

JPS 61-211342 A — Asahi Chemical, ultrafine polymer particles

• Full citation: JP S61-211342 A, Asahi Chem Ind Co Ltd, "Production of ultrafine high-molecular material particle" (listed under "Family Cites Families (1)"). Priority 1985-03-15; published 1986-09-19. Source: Google Patents family table for US5118528A.
• Why it matters: It is cited against a member of the '528 family (not against the US case), it is titled to production of ultrafine high-molecular (polymer) material particles, and it published 1986-09-19 — before the 1986-12-31 priority date. If it discloses mixing a polymer solution with a non-solvent, it is a prime §102 candidate against claims 15 and 16 (and, to the extent it uses an active substance, claim 1).
• §102 assessment (provisional): Unverified full text. Treat as a high-priority anticipation candidate for the polymer-only independent claim 15.

4. Background art recited inside the specification (not in the citation list)

These are expressly discussed as prior art by the '528 applicants and are therefore admitted art:

5. Bottom line

Most relevant prior art: DE 738,604 C (Degkwitz, 1943), followed by CH 201,942 A (Krause, 1938) for the general "organic solution → aqueous medium + surfactant → evaporate solvent" process, and then by WO 1986/003676 A1 and JPS 61-211342 A as the two documents most likely to ripen into genuine §102 anticipation of the polymer claims once their full texts are read.

No single reference in the citation list discloses every element of independent claim 1 or claim 15 — in particular the combination of (i) a film-forming material and a biologically active substance, (ii) a non-solvent miscible in all proportions with the solvent, (iii) substantially instantaneous precipitation, and (iv) a matrix-type, spherical particle below 500 nm. The realistic invalidity theory is §103, anchored on DE 738,604 C and/or CH 201,942 A in view of Marty (NPL desolvation) and US 4,492,720 A (drug + matrix polymer dissolved in a common solvent), not §102.

6. Limits of this analysis (stated explicitly)

• I based the reference list on the authoritative record you supplied rather than a live USPTO Patent Center retrieval; I could not execute a PatentCenter/Global Dossier query within the available search steps. The USPTO/PatentCenter, Assignment and Espacenet links appear on the Google Patents record at https://patents.google.com/patent/US5118528/en.
• Full text and claims were verified only for CH 201942 A, DE 738604 C, US 3691090 A and US 4492720 A. US 4585651 A, WO 1986/003676 A1, AU 495261 A and JPS 61-211342 A were not verified — their §102 conclusions above are explicitly provisional and must be confirmed against the primary documents (and, for JPS 61-211342 A, against a certified translation) before being relied on.
• I did not auto-correct any identifier; "CH201942A," "DE738604C," "AU495261A," "US3691090A," "US4492720A," "US4585651A," "WO1986003676A1," "JPS61211342A" and "US5118528A" are all reproduced exactly as they appear in the source record.
• The citation table in the supplied text carries the legend "* Cited by examiner, † Cited by third party" but does not show the per-row markers, so I cannot state which of the seven citations were examiner-applied versus third-party-applied, nor which were merely listed as "technological background" (A-category) versus cited for materiality (X/Y).

I'll ground this analysis in the references listed on the patent page, verifying what I can about each reference's actual disclosure before building § 103 combinations.

Good — I have solid detail on Mosier and the Ohio State reference. Let me verify the remaining record references.

Two more targeted searches to pin down the Asahi family reference and the Fuji reference.

Obviousness Analysis — US 5,118,528 (Fessi et al.) under 35 U.S.C. § 103

Scope note. As instructed, this analysis uses the prior-art references appearing on the US 5,118,528 patent page (the "Patent Citations (7)" table and the family-citation table) plus the applicant-admitted prior art in the specification. I have verified the actual disclosure of three of the seven record references and flag explicitly where I could not. All identifiers are reproduced literally; nothing has been corrected. Because the patent has a 1986-12-31 priority date (FR 8618446) and a 1987-12-31 U.S. filing, the pre-AIA version of § 102/§ 103 governs, and the critical date for printed publications is December 31, 1986.

1. Claim-element breakdown (the target)

The two independents are the whole ballgame. Everything else is a range/ancillary limitation.

Claim 16 = claim 15 where the polymer is polylactic acid. Claim 14 = diameter "about 200 nm."

Internal-consistency flag (carried over, not corrected): claim 1 recites a "greater volume of a second liquid phase," while dependent claim 5 recites a "lesser amount of non-solvent … than solvent." Read literally these point opposite ways. In § 103 terms this matters, because the "greater volume of non-solvent" limitation is one of the few places a challenger must actually reach for art; if claim 5 is taken at face value, the po