US 6268053

I'll search for current docket and litigation information, then compile the summary.

US 6,268,053 B1 — Analyst Summary

Scope note / number literalism. I searched USPTO-derived and public docket sources for the literal number 6268053. Several other identifiers collide with that digit string and must not be conflated with US 6,268,053:

The entity in the search hits that does refer to US 6,268,053 is the Epic Therapeutics / Baxter "macromolecular microparticles" family (cited as prior art in later filings such as the EP 2,774,935 A1 and RU 2,457,854 C2 references I retrieved).

Bibliographic data (per the Google Patents record)

Continuity chain (from the specification): 09/483,657 is a continuation of 08/699,586 (filed 1996-08-19, now US 6,090,925), which is a continuation-in-part of 08/206,456 (filed 1994-03-04, now US 5,578,709), which is a continuation-in-part of 08/028,237 (filed 1993-03-09, now abandoned). This family is the reason the '053 specification appears nearly verbatim in sibling U.S. patents and in EP 0 688 429 B1 / EP 0 809 110 A1.

Abstract

"Microparticles formed by mixing a macromolecule with a polymer at a pH near the isoelectric point of the macromolecule and incubating the mixture in the presence of an energy source for a predetermined length of time. The microparticles are composed of homogeneously distributed, intertwined macromolecule and polymer. Each microparticle allows aqueous fluids to enter and allows solubilized macromolecule and polymer to exit the microparticle and may be formulated to provide a sustained release of macromolecule and polymer from the interior of the microparticle when placed in an appropriate aqueous medium, such as under physiological conditions. Methods of production and methods of use for research, diagnostics and therapeutics are provided."

⚠️ Discrepancy flagged: the abstract text captured from the Google Patents page in the supplied authoritative text is truncated to a generic two-sentence placeholder ("Methods relating to the field of biochemistry…"). The complete abstract above comes from the Justia and Typeset mirrors of the same document. I'm treating the fuller version as the substantive abstract but noting the mirror inconsistency.

Plain-language overview

The patent covers an aqueous, organic-solvent-free way of turning proteins/peptides/nucleic acids/other macromolecules into small solid spheres, and the spheres themselves.

• Core process: mix the macromolecule with a soluble polymer (e.g., PVP + PEG, or dextran) in water, adjust pH to near the macromolecule's isoelectric point, then apply energy (typically heat, ~37–90 °C for minutes to hours) so the polymer dehydrates/excludes water from the macromolecule, causing it to collapse into a microparticle.
• Key structural twist: unlike PLGA microspheres, here the macromolecule is the majority component of the particle (≥40% and <100% by weight), with polymer ≤30%. The two are "intertwined"/homogeneously distributed in a water-soluble matrix.
• Release behavior: the particle is permeable; aqueous fluid enters and solubilized macromolecule/polymer diffuses out, giving sustained release that can be tuned by polymer type/concentration, temperature, pH, and incubation time — and can be made to avoid the "burst effect."
• Applications claimed in the specification: separations/affinity chromatography, diagnostics and immunoassays, targeted and sustained drug delivery (leuprolide, nafarelin, insulin, LHRH, doxorubicin), vaccines/adjuvants, gene delivery, and in vivo/histopathological imaging.

Independent claims — ⚠️ uncertainty

I do not have authoritative, verified claim text for US 6,268,053 specifically, and I will not reconstruct it. The full text supplied to me ends within the "Detailed Description" and does not include the claims section; my searches returned claim language only for the parent, US 6,090,925 (e.g., its claim 20 "A method of making microparticles comprising combining a macromolecule and a polymer in an aqueous solution at a pH near the isoelectric point…", claim 21 "A microparticle prepared by a method comprising…", and claim 43 "A method for delivering a therapeutic agent…"). Those are different claims in a different patent and should not be attributed to '053.

What I can say with reasonable confidence, grounded in the '053 specification and its classification profile (A61K 47/6929 nanoparticle/solid-microparticle classes, C07K 1/30 precipitation-as-complexes, G01N 33/54313 particulate immunoassay carriers), is that its independent claims are expected to fall into these categories — stated here as inference, not verified fact:

1. A composition-of-matter claim to the microparticle itself, characterized by the macromolecule-rich (≥40 wt%) intertwined macromolecule/polymer matrix and the pH-near-pI/energy-source formation route.
2. A method-of-making claim (combine macromolecule + soluble polymer at pH near pI → expose to energy source → recover microparticles).
3. One or more method-of-use claims for diagnostic/therapeutic/research applications (delivery of a therapeutic agent, isolating a target molecule, detecting a target biomolecule).
4. Possibly a kit claim.

Anyone relying on this for a freedom-to-operate or invalidity analysis must pull the actual granted claim set from USPTO PatentCenter / the printed patent, since the patent is expired (2013-03-09) but its disclosure is heavily cited in later microparticle patents.

Litigation / CAFC 2026 check

No CAFC docket or 2026 appellate activity involving US 6,268,053 was found. My searches of Federal Circuit 2026 docketing notices and 2026 patent litigation reporting returned unrelated matters — Contour IP Holding v. GoPro (No. 2026-2012), Teva v. Lilly (No. 2024-1094), STX v. StringKing, Nearby Systems v. Exxon Mobil, and ParkerVision updates — none of which assert the '053 patent. Patent-term math is consistent with this: the patent's anticipated expiration was 2013-03-09 (the 20-year term ran from the 1993-03-09 priority chain; the file history additionally shows a terminal disclaimer and an express abandonment-after-allowance followed by an RCE in late 2000), so the '053 patent has been expired for over a decade and is not a live asserted patent.

Separately, I did see "Epic Therapeutics" / "EPIC" appearing in D. Del. Hatch-Waxman litigation against Baxter, but that involves a different entity's patents — US 9,993,520, 11,135,265, and 11,207,372 (vasopressin formulations) — not the Epic Therapeutics microparticle portfolio and not the '053 patent. Do not conflate them.

Bottom line

US 6,268,053 is a Baxter/Epic Therapeutics-era patent (Woiszwillo et al.) on macromolecule-rich, polymer-dehydrated microparticles formed by near-pI, heat-driven volume exclusion in aqueous solution, with sustained-release and diagnostic/therapeutic uses. It issued 2001-07-31 from application 09/483,657, expired 2013-03-09, and shows no 2026 CAFC activity. The one item I could not verify authoritatively is the exact granted independent claim text, which is absent from the supplied document and should be confirmed against the official USPTO copy.

I'll search litigation databases and patent sources for US patent 6268053.

Let me dig deeper with more targeted searches.

Let me check specific litigation databases and the patent's family for related suits.

Litigation Search: U.S. Patent No. 6,268,053

Bottom line

I found no evidence of any litigation (district court, ITC, or PTAB/reexamination) specifically involving U.S. Patent No. 6,268,053. Based on the sources searched, no case appears to have asserted this patent.

About the patent (context for the search)

• Number: 6,268,053 B1 — "Macromolecular microparticles and methods of production and use"
• Inventors: Woiszwillo, Brown, Scott, Di, Sudhalter, Blizzard, Riske
• Original assignee: Epic Therapeutics, Inc. (Norwood, MA); later assigned to Baxter International Inc. / Baxter Healthcare SA (recorded 2003-06-10)
• Filing date: Jan. 14, 2000 (continuation of Ser. No. 08/699,586, now U.S. Pat. No. 6,090,925, which is a CIP of Ser. No. 08/206,456, now U.S. Pat. No. 5,578,709, a CIP of Ser. No. 08/028,237 filed Mar. 9, 1993)
• Grant date: July 31, 2001
• Legal status: Expired – Lifetime (anticipated expiration March 9, 2013)
• Field: Protein/macromolecule microparticles formed by mixing a macromolecule with a soluble polymer near the macromolecule's isoelectric point in the presence of an energy source; sustained-release drug delivery, diagnostics, separations

What the searches returned

• No complaint, docket, or judgment was located naming 6,268,053 as a patent-in-suit.
• The patent appears in the record only as prior art / a cited reference in other patents (e.g., EP 2774935 A1, JP 2012500118 A, EP 2429493 B1, RU 2457854 C2) — these are citation relationships, not litigation.
• Its family members/continuations (e.g., U.S. Pat. Nos. 6,090,925, 5,578,709, 6,458,387, and the EP equivalents EP 0688429, EP 1060741) likewise did not surface as asserted patents in the results.

Important caveat — do not conflate similar numbers

Several search hits involve Baxter and a patent referred to as the "'805 patent," but those are different patents, and I am flagging them so they are not mistakenly attributed to 6,268,053:

Note that a numeral string as innocuous as "805" attaches to many unrelated patents; none of the above is U.S. 6,268,053.

Confidence and limitations

• Confidence that no litigation is known: high, but not absolute. I could not exhaustively query every paywalled docket system. Unified Patents' litigation portal, Justia's patent page, CourtListener/Google Scholar case text, PTAB records, and general web sources returned no case asserting 6,268,053.
• Basis for the likely absence of suits: the patent expired in March 2013 (20-year term from the 1993 priority chain), which is well before the current date and reduces the likelihood of any active enforcement. Its cited role in the literature is as a foundational microsphere reference, not as an asserted patent.
• I did not fabricate any case, party, jurisdiction, or case number. Where I could not find a fact, I have said so.

Recommended next steps to confirm

Because you asked for litigation-grade certainty, I would verify against these primary sources directly (I could not fully query the paywalled ones):

1. PACER / CourtListener RECAP — full-text docket search for "6,268,053" and "6268053."
2. Unified Patents Portal (portal.unifiedpatents.com/litigation) — patent-level litigation tab for 6,268,053.
3. Lexis CourtLink / Westlaw KeyCite — patent history report (the same method the USPTO's CRU uses for its "Litigation Search Report").
4. USPTO Patent Center / Global Dossier — reassignment and any reexam/reexam certificate history (the 2003 assignment to Baxter is confirmed; no reexam was surfaced).

If you'd like, I can run targeted queries against any specific one of these once search access is available, or check the family members (6,090,925; 5,578,709; 6,458,387) for litigation, since a party enforcing the platform would more likely assert those.

Disclaimer: This is an informational search summary, not legal advice or a legal conclusion on the patent's status, ownership, or any party's rights.

I'll verify the structured data with web searches before drafting.

Let me run more targeted searches to confirm the absence of PTAB activity.

PTAB / AIA Trial Proceedings — US Patent 6,268,053 ("Macromolecular microparticles and methods of production and use")

Proceedings overview

There are zero AIA trial proceedings on file for US 6,268,053. The structured "PTAB proceedings on file" block — sourced from the USPTO Open Data Portal — returns no IPR, PGR, or CBM, and my independent web searches (Google Patents, Unified Patents' patent portal, RPX/PTAB document mirrors, Docket Alarm, and general PTAB-decision search) surfaced no petition, institution decision, final written decision, or appeal naming this patent. There is therefore no active/claims-invalidated/claims-sustained/settled/institution-denied breakdown to report — every bucket is empty.

Bottom-line defensive posture: the patent was never tested at the PTAB, so a defendant gets no free invalidating FWD to point at — but that is largely academic, because US 6,268,053's legal status is "Expired – Lifetime" with an anticipated expiration of 2013-03-09 (per Google Patents, https://patents.google.com/patent/US6268053/en). An expired patent cannot support prospective injunctive relief and its infringement exposure is limited to the § 286 six-year damages lookback, which for this patent ran out in 2019. The absence of PTAB activity is not evidence of a hardened patent here — it is consistent with a patent that simply aged out of commercial assertion before the AIA trial bar became the default first move.

No proceedings to itemize — what I verified instead

Because there is no proceeding number to put in the ### {PROCEEDING_NUMBER} template, I will not manufacture one. What follows is the verification record and the adjacent-risk analysis.

Verification record (searched 2026-09-27)

Distractors I affirmatively ruled out (do not confuse these with a proceeding on the '053 patent — the numbers are similar but the patents are different):

• IPR2020-00992, SK Innovation Co., Ltd. v. LG Chem, Ltd. — challenges US 8,012,626, not '053. (CourtListener/Docket Alarm also indexes this case as "IPR_Petition_626", which is a search-engine trap.)
• IPR2017-01587 — concerns US 9,149,626 (catheter/needle-safety art), unrelated field.
• IPR2017-01100, Actavis LLC v. Abraxis Bioscience LLC — albumin-particle art that cites the '053 family as background (e.g., WO 94/18954, US 5,525,519), but the challenged patent is an Abraxis one, not '053. Do not cite this as an '053 FWD.

Why the AIA-trial toolbox was narrow for this patent anyway

Even had a challenger wanted to file, the available vehicles were limited by the patent's pedigree:

• PGR: unavailable. PGR applies only to patents with at least one claim having an effective filing date on or after 2013-03-16. US 6,268,053 claims priority to 1993-03-09 (application 08/028,237 → 08/206,456 → 08/699,586 → this continuation 09/483,657, filed 2000-01-14). It is squarely a pre-AIA patent. (See the priority chain recited at the top of the specification.)
• CBM: unavailable in substance. CBM review required a "covered business method" patent — one claiming a technique used in the practice, administration, or management of a financial product or service. The '053 claims are directed to protein/polymer microparticle formation for separations, diagnostics, and drug delivery (see the summary of the invention). It is not a financial-services patent, so § 18 of the AIA would not have applied.
• IPR: the only realistic route. An IPR would have had to be filed within one year of service of an infringement complaint (§ 315(b)) and would have been limited to § 102/§ 103 grounds on patents and printed publications. No such petition was filed.

Strategic summary

Claim-level posture. The task cannot be answered at claim granularity because no adjudicative body has ever construed, canceled, or confirmed any claim of US 6,268,053 in an AIA trial. Correspondingly, no claim is "canceled," no claim is "sustained by the PTAB," and there is no FWD from which to quote a disposition. I will not assign a claim number to any status — the claim set is not even reproduced in the authoritative patent text supplied in this prompt, and inventing one would be fabrication. Practically speaking, the whole claim set is untested at the PTAB, and the patent is expired as of 2013-03-09 (Google Patents legal status: "Expired – Lifetime").

Estoppel landscape. Because no IPR/PGR/CBM was ever instituted, § 315(e)(2) estoppel does not exist for any party with respect to this patent. There is no petitioner (and therefore no privy or real party in interest) who is precluded from raising any § 102/§ 103 ground — the entire body of prior art remains procedurally available to a would-be challenger in a district court or ITC action. Conversely, there is no PTAB record to help a defendant either: no institution decision to cite for a § 325(d) argument, no FWD to quote, and no claim-construction ruling to borrow at Markman. What a challenger has instead is a fully open art canvas — and, because the patent expired in 2013, only a time-barred damages theory worth litigating.

Pattern signals. There is nothing to read as a pattern on this patent: no repeat petitioner, no serial IPR filings, no PTAB-side Patent Owner appeals, and no defensive aggregator (no Unified Patents, RPX, or similar) in the chain. The only "chain" evident from the file is corporate: original assignee Epic Therapeutics, Inc. (of the PROMAXX® protein-matrix technology), assignment to Baxter International Inc. / Baxter Healthcare SA recorded 2003-06-10, matching the assignee-of-record shown on Google Patents and Unified Patents' portal. The '053 patent is heavily cited in later pharmaceutical-particle patents (e.g., the 2005–2010 Baxter/Eastman PROMAXX family filings that list U.S. Pat. Nos. 5,525,519; 5,554,730; 5,578,709; 5,981,719; 6,090,925; 6,268,053; and 6,458,387 together), which is a citation-network signal, not a litigation or IPR signal.

Honest limits. I could not access the USPTO PTAB E2E docket directly in this session (no indexed case to open), and I cannot rule out a petition that was filed but never docketed/indexed, or a district-court validity challenge that never went to the Board. My conclusion is based on the canonical ODP block plus multiple public indexes agreeing on zero.

Recommended next steps

If you are a defendant and the demand letter or complaint cites US 6,268,053:

1. Lead with the expiration date, not the PTAB. Check the face of the patent and PAIR for the actual expiration/terminal-disclaimer math, but Google Patents states an anticipated expiration of 2013-03-09, with legal status "Expired – Lifetime" (https://patents.google.com/patent/US6268053/en). Any damages claim is confined to § 286's six-year lookback; on these dates that reaches back at most to 2020 — i.e., after expiration. Ask opposing counsel to identify the accused acts and their dates in writing.
2. There is no FWD to cite. Do not represent to a court that any claim "was canceled by the PTAB" — it was not, and there is no opinion at PTAB E2E (https://ptacts.uspto.gov) or on CourtListener (https://www.courtlistener.com) to link. Your validity defense is a clean slate: whatever § 102/§ 103 art you have is free of § 315(e)(2) estoppel, because no petitioner ever appeared.
3. Because the patent is pre-AIA, your invalidity theory must respect pre-AIA § 102/§ 103 law, and you cannot rely on AIA-conforming priority analysis to knock out the 1993-03-09 priority date. If, on the other hand, you want the earlier priority date to attach (e.g., to reach pre-1993 art), note the family's priority is 1993-03-09 through the '237 application — the specification expressly recites the chain.
4. Check the family too. The '053 is one node in a dense family (U.S. Pat. Nos. 5,525,519; 5,554,730; 5,578,709; 5,981,719; 6,090,925; 6,458,387, among others). A demand letter may be asserting a continuation or sibling, not '053. Confirm the exact patent number before relying on the "no PTAB activity" finding, since my search was scoped to 6,268,053 specifically and I did not verify trial history on every family member.
5. If any active proceeding does exist that I could not find: the statutory clock is one year from institution to FWD (§ 316(a)(11)), institution is decided within six months of the petition's filing (§ 314(b)), and joinder/termination requests are separately docketed. Send me the proceeding number and I will pull the institution decision, panel, and claim-level disposition.

Plainest version: there is no PTAB proceeding on this patent to brief. The patent's real vulnerability today is not a canceled claim — it is expiration on 2013-03-09, which for practical purposes ends the fight.

I'll research the assignment record and surrounding corporate history before reconstructing the chain.

Let me look for the specific reel/frame data and any later transfers (e.g., Baxalta/Shire spin-offs).

Assignment & Ownership Analysis — US 6,268,053 B1

Data-access caveats (read first). I was able to retrieve the patent document itself (Google Patents, https://patents.google.com/patent/US6268053/en) and confirm the two ownership events it lists, but the Assignment Center / assignment.uspto.gov records were not retrievable in this session (the search endpoint returned no records on direct query, and follow-up queries were rate-limited). Consequently:

• Reel/frame numbers are NOT reported below — I will not guess them. Google Patents' legal-events mirror does not display reel/frame.
• Correspondents of record are NOT reported — also not exposed by the mirror, and fabricating an attorney/firm would be a false finding.
• Everything below that is stated is grounded in the patent front matter, Google Patents legal events, and press/business sources cited inline. Treat the reel/frame and correspondent columns as open items to pull manually at https://assignment.uspto.gov/patent/index.html (search by patent number) and https://assignmentcenter.uspto.gov/.

Inventors

Seven named inventors on US 6,268,053:

Pattern note (unusual, but benign): this application is a continuation chain — filed 2000-01-14 as Ser. No. 09/483,657, continuing Ser. No. 08/699,586 (filed 1996-08-19, now US 6,090,925), which was a CIP of Ser. No. 08/206,456 (filed 1994-03-04, US 5,578,709), itself a CIP of Ser. No. 08/028,237 (filed 1993-03-09, abandoned). The inventor→company assignment was therefore recorded in April 2000, ~7 years after the 1993 priority date and ~3 months after the 2000 continuation was filed — a confirmatory/clean-up assignment typical of continuation practice. The 1993–1996 priority filings were likely covered by assignments recorded against the earlier-issued parents (US 5,578,709, US 6,090,925); I could not verify those parent records here.

No departure pattern observed. There is no evidence of all inventors leaving the original assignee within 12 months of filing. To the contrary, the inventive team was still inside Epic Therapeutics when Baxter acquired the company in 2002 (Brown was still publicly identified as Epic's CTO at acquisition time).

Original assignee

Epic Therapeutics, Inc. — named original assignee on the issued patent (Google Patents front matter; current assignee listed as Baxter Healthcare SA / Baxter International Inc.).

• Primary business: privately held drug-delivery company, HQ 220 Norwood Park South, Norwood, MA; ~38 employees at acquisition. Developed the PROMAXX / ProMaxx water-based protein-microsphere technology (the commercial embodiment of the claims in this family), lead product LeuProMaxx (leuprolide, 28-day and 84-day formulations) plus PROMAXX inhaled insulin. (Sources: Baxter/Epic acquisition press release, 2002-11-11; Pharmaceutical Technology "In the Field" profile; Chicago Tribune 2002-11-12.)
• Product shipped? Partially — the platform was scaled to cGMP and licensed/used for clinical programs; whether LeuProMaxx ever obtained FDA approval is not verified here. Baxter later (2007) presented Phase I inhaled-insulin results using PROMAXX.
• Current status: Acquired and dissolved as a separate entity. Baxter Healthcare Corp. signed a definitive agreement 2002-11-11 to acquire Epic for $50–100M, closing Q4 2002 (Chicago Tribune; Memphis Business Journal; PRNewswire 2002-11-11). Epic operated as a Baxter subsidiary. Note: Tracxn and other databases indicate Epic was formerly Middlesex Sciences — a possible change-of-name event that I could not confirm as a recorded assignment against this patent.

Assignment timeline

Two ownership events are visible on the patent's legal-events record. Reel/frame and correspondent were not retrievable (see caveat above); execution dates are not exposed by the mirror.

• Execution date not exposed / recorded 2000-04-25 — Reel/frame not retrieved

  • Conveyance: Assignment (inventor → company)
  • Assignor: Woiszwillo, James E.; Brown, Larry R.; Scott, Terrence L.; Di, Jie; Sudhalter, Judith; Blizzard, Charles D.; Riske, Frank J. (all seven named inventors)
  • Assignee: Epic Therapeutics, Inc.
  • Correspondent: not retrieved
  • Context: Initial inventor-to-company assignment; recorded ~3 months after the 2000-01-14 continuation filing — a confirmatory chain-of-title filing, not a transfer to a third party.

• Execution date not exposed / recorded 2003-06-10 — Reel/frame not retrieved

  • Conveyance: Assignment (M&A / corporate acquisition)
  • Assignor: Epic Therapeutics, Inc.
  • Assignee: Baxter International Inc. and Baxter Healthcare SA (a corporation of Switzerland) — joint assignees, the standard Baxter U.S. parent + Swiss holding pairing
  • Correspondent: not retrieved
  • Context: Acquisition — Baxter's purchase of Epic Therapeutics (~$50–100M, announced 2002-11-11, closed Q4 2002; recorded at USPTO 2003-06-10).

No later assignments are visible on the sources I reached. Google Patents records the patent as "Expired – Lifetime," anticipated expiration 2013-03-09. Because the term ended in 2013, the Baxter biopharma spin-off chain (Baxalta 2015 → Shire 2016 → Takeda 2019) is not expected to touch this patent, and I found no evidence that it did. (Unverified — I could not confirm by direct PEDS/ODP query.)

Timeline diagram

timeline
    title Ownership of US 6268053
    1993 : Priority application filed
    2000 : Continuation application filed
         : Inventors assign to Epic Therapeutics
    2001 : Patent US6268053 issues
    2002 : Baxter signs deal to acquire Epic
    2003 : Epic assets assigned to Baxter
    2013 : Patent term expires

NPE / troll-pattern signals

1. Shell-entity transfer — not present. The only post-issuance transfer (recorded 2003-06-10) moved the patent from an operating drug-delivery company to Baxter International Inc. / Baxter Healthcare SA, a NYSE-listed operating manufacturer. No "IP / Holdings / Ventures / Licensing" suffix appears anywhere in the chain. No registered-agent-service address is evidenced.
2. Known asserter in the chain — not present. Neither Epic Therapeutics nor Baxter International/Baxter Healthcare SA appears on the enumerated NPE list (Acacia, Marathon, IV, IPNav, Wi-LAN, Conversant, Vringo, Pendrell, Innovatio, MPHJ, Lumen View, Round Rock, Document Generation Corp, Spangenberg entities). No RPX/Unified high-frequency-plaintiff match surfaced in my searches; Baxter is not an NPE.
3. Repeat correspondent across the chain — unclear / not verifiable. The correspondent of record is not exposed by the sources I could reach, and both events were unretrievable from the Assignment Center. No correspondent finding can be made. This is the single most important item to pull manually; if the 2000 and 2003 recordings share a correspondent it is almost certainly ordinary Baxter/Epic outside-counsel continuity, not an NPE broker.
4. Cascading transfers — not present. Exactly two recorded events span 1993–2003; there is no chain of LLCs, and no cluster of transfers within <24 months.
5. Pre-litigation transfer — not present. I found no infringement litigation naming US 6,268,053 on the sources searched, and no transfer within 6 months of any suit. (Caveat: a full Docket Navigator / PACER / RPX run was outside this session's reach.)
6. Bankruptcy fire-sale — not present. Epic Therapeutics was acquired at a negotiated price ($50–100M), not sold in bankruptcy; Baxter is solvent and operating.
7. Privateering — not present. Baxter acquired the entire company (38 employees, the Norwood R&D site, and the PROMAXX platform) for in-house drug-delivery service offerings — the opposite of transferring a patent to a proxy asserter while the operating company stays out of court. No evidence of Baxter-funded assertion against competitors.
8. Defensive aggregator — not present. The chain terminates at Baxter, not at RPX, AST, LOT Network, Unified Patents, or OIN. Inverse signal (neutralization) does not apply.

Verdict

Insufficient data — no NPE pattern detected.

Justification: only two ownership events are on record — the inventor→Epic Therapeutics assignment and the recorded 2003-06-10 assignment of Epic's rights to Baxter International Inc. and Baxter Healthcare SA — and the chain then runs unbroken to the patent's 2013-03-09 expiration. The last assignee is a large, solvent, product-shipping operating company that bought Epic in a negotiated $50–100M transaction, and none of the eight NPE signals is affirmatively present. I stop short of a clean "operating-company / non-asserting" call only because the enumerated verdict buckets have no slot for "operating company, no assertion evidence," and because reel/frame and correspondent could not be verified in this session — pull those two fields manually before treating this as final.

Verify at: https://assignment.uspto.gov/patent/index.html (search "6268053") and https://assignmentcenter.uspto.gov/ — confirm (a) reel/frame for each of the two entries, (b) the correspondent of record on each, and (c) whether any post-2013 record exists (not expected, since the term expired).

I'll research the actual cited references for US 6,268,053 and verify each reference's details.

Let me pull the specific cited-reference list and the claim set for US 6,268,053.

Prior-Art Analysis — US 6,268,053 B1

Patent: "Macromolecular microparticles and methods of production and use" — Woiszwillo, Brown, Scott, Di, Sudhalter, Blizzard, Riske; App. 09/483,657 filed 2000-01-14; issued 2001-07-31; assignee Baxter Int'l / Baxter Healthcare SA (orig. Epic Therapeutics); expired 2013-03-09. Source: https://patents.google.com/patent/US6268053/en

0. Scope, method, and two hard limits you must read first

Limit 1 — the claim set is not in the authoritative text. The supplied full text of US 6,268,053 ends inside the "Detailed Description" (I verified this: the document truncates after the label/reporter discussion). No claims section is present. My earlier-generated sections flagged this, and I confirm it here. Consequence: I cannot assign an anticipation finding to a specific claim number without fabricating one. Everything below is mapped to claim categories (composition / method-of-making / method-of-use / kit), reconstructed from the specification's own "Summary of the Invention" and "objects" statements. When you pull the printed patent, drop the actual claim numbers into § 8's matrix.

Limit 2 — the on-face "References Cited" tables were not retrievable. The Google Patents HTML I hold is truncated before the front-page reference tables, and my searches were cut off before I could exhaustively retrieve the USPTO PTO-892 / IDS list. What I could verify from third-party mirrors of the '053 record (Justia citation table) is that US 5,567,435 (Hubbell), US 5,578,709 (Woiszwillo) and US 6,090,925 (Woiszwillo et al.) appear in the '053 citation table. The remaining patent citations below are taken from the body of the '053 specification, where they are expressly discussed — those I can quote with confidence.

Number literalism (already flagged in prior sections, repeated for safety). Do not conflate the string "6268053" with: OSTI ID 6268053 (= US 4,802,384, Deere & Co.), MaRDI Publication:6268053 (a 2015 number-theory paper), or JP 6268053 (an LED fixture). None is this patent.

1. The controlling legal framework (pre-AIA)

US 6,268,053 is a pre-AIA patent (priority 1993-03-09; filed 2000-01-14 — before the first-inventor-to-file provisions took effect, and its claims have no post-2013-03-16 effective filing date). Therefore:

• § 102(a)/(e) require the reference be "by another" — a different inventive entity (In re DeBaun). A reference naming only Woiszwillo is formally "by another" relative to the seven-inventor '053 entity, but formally only.
• § 102(b) has no "by another" requirement — a printed publication or patent by the very same inventors more than one year before the effective filing date is a statutory bar (In re Katz). This is the single most important hook for the Woiszwillo-authored documents.
• § 102(e) (pre-AIPA for references filed before 2000-11-29) gives a U.S. patent an as-of-its-filing-date prior-art effect if "by another" and if the reference is not an application/patent from which the challenged application claims § 120 benefit.
• Pre-AIA § 103(c) disqualifies commonly-owned § 102(e)/(f)/(g) art from obviousness (not anticipation) where common ownership existed at the time the invention was made. Epic Therapeutics/Baxter owned the whole family — this guts most § 103 uses of the family references.
• Anticipation requires one reference disclosing every limitation arranged as in the claim (Net MoneyIN v. VeriSign).

1.1 The effective-filing-date ladder — the pivot of the whole analysis

Because '053 sits at the end of a CIP chain, the § 102(b) bar date and the § 102(e) cutoff move claim by claim, depending on whether that claim's subject matter is supported by the earlier disclosures.

The chain is stated on the face of the '053 specification, which I have verbatim: "a continuation of application Ser. No. 08/699,586 … now U.S. Pat. No. 6,090,925, which is a continuation-in-part of application Ser. No. 08/206,456 … U.S. Pat. No. 5,578,709, which is a continuation-in-part of application Ser. No. 08/028,237, filed Mar. 9, 1993, abandoned."

Practical consequence: a reference published/issued in the window 1993-03-09 → 1995-08-19 is not prior art against claims entitled to the 1993 date, but becomes 102(b) statutory-bar art against any claim lacking 1993 written-description support. That window contains the most dangerous reference in the file — WO 93/14110.

2. The patent citations — master table

Legend: [V] = date verified in this session against a fetched document; [S] = citation verified as on/in the '053 record (specification text or Justia citation table), bibliographic date stated from standard records and should be re-verified.

Verbatim from the '053 specification (background section), so you can see exactly how these are characterized: "Exemplary polymers used for the formation of microspheres include homopolymers and copolymers of lactic acid and glycolic acid (PLGA) as described in U.S. Pat. No. 5,213,812 to Ruiz, U.S. Pat. No. 5,417,986 to Reid et al., U.S. Pat. No. 4,530,840 to Tice et al., U.S. Pat. No. 4,897,268 to Tice et al., U.S. Pat. No. 5,075,109 to Tice et al., U.S. Pat. No. 5,102,872 to Singh et al., 5,384,133 to Boyes et al., 5,360,610 to Tice et al., and European Patent Application Publication Number 248,531 to Southern Research Institute; block copolymers such as tetronic 908 and poloxamer 407 as described in U.S. Pat. No. 4,904,479 to Illum; and polyphosphazenes as described in U.S. Pat. No. 5,149,543 to Cohen et al."

This characterization is dispositive for the anticipation question. Every item in rows 6–17 is cited by the '053 specification as the PLGA/liposome/polyphosphazene prior art whose deficiencies the invention overcomes — organic-solvent processing, poor loading, burst release, large/aggregated particles, multi-µm liposomes. The applicant cited them as context, not as close art.

3. Reference-by-reference: description and § 102 assessment

3.1 WO 93/14110 (Woiszwillo; Middlesex Sciences) — the highest-value reference

Full citation: Woiszwillo, J.E., "Method for isolating biomolecules with linear polymers," PCT/US93/00073, International Publication No. WO 93/14110 A1; priority US 07/817,610 filed 1992-01-07; international filing date 1993-01-07; published 1993-07-22; applicant Middlesex Sciences, Inc. (Mansfield, MA). U.S. counterpart: US 5,525,519. Verified via PubChem (https://pubchem.ncbi.nlm.nih.gov/patent/WO-[9314110](/patent/9314110)-A1), the Hungarian national-phase publication HU T65139 A, and AU 667508 B2 (IPC C07K 3/24, G01N 33/68).

Description (from the AU abridgment, verbatim): "A method, composition, and kit for isolating biomolecules from a biological sample wherein the sample is mixed with a soluble, linear polymer, such as polyvinylpyrrolidone, to form a precipitate. The biomolecule of interest is found in the precipitate or is isolated from the supernatant."

Why the '053 applicant cited it: the '053 specification says "the polymer or polymer mixture may be prepared in accordance with the methods set forth in U.S. Pat. No. 5,525,519 to James E. Woiszwillo, or PCT Patent Application No. US93-00073 (International Publication No. WO 93/14110), filed Jan. 7, 1993 and published on Jul. 22, 1993." So it is cited as a polymer-handling teaching, i.e., as a § 103 support reference — a tell that the applicant did not regard it as anticipatory.

§ 102 assessment:

• Not § 102(a) — published 1993-07-22, after the 1993-03-09 constructive reduction to practice; a later publication cannot be 102(a) art.
• Not § 102(b) against claims entitled to 1993-03-09 or 1994-03-04 — the bar dates are 1992-03-09 and 1993-03-04 respectively; 1993-07-22 postdates both.
• IS § 102(b) against any claim whose only support is the 1996-08-19 or 2000-01-14 filings (bar dates 1995-08-19 and 1999-01-14 — 1993-07-22 comfortably precedes both).
• No § 102(e) date. Pre-AIPA international applications got no § 102(e) benefit; the AIPA change (applications filed on/after 2000-11-29, published in English) does not reach a 1993-filed PCT. [Flag: verify against MPEP 2136.03 in your jurisdiction's practice.]
• "By another"? Woiszwillo is a common inventor, but the '053 entity is Woiszwillo + 6 others, so the entities differ (In re DeBaun) — for § 102(b) this is academic anyway.
• Would it anticipate? Only if a '053 claim is drafted broadly enough to read on "contacting a macromolecule with a soluble linear polymer (e.g., PVP) to form a precipitate," or on a kit claim for the same. Its disclosure is a macromolecule isolation/precipitation method; it does not disclose (i) a discrete microparticle <10 µm of uniform spherical shape, (ii) a macromolecule ≥40 wt% / polymer ≤30 wt% composition, (iii) pH adjustment to within ~1.5–4 units of the macromolecule's pI, or (iv) incubation at a temperature above room temperature as the particle-forming energy source. Those four limitations are the novelty core of the '053. Verdict: anticipates only a hypothetical over-broad broadest claim; otherwise § 103 art (and, if it is the same family, watch for § 102(b) self-collision on late-supported claims).

3.2 US 5,567,435 — Hubbell et al. (1996-10-22) — in the '053 citation table

Description: "Gels for encapsulation of biological materials" — photopolymerizable water-soluble macromers crosslinked by free-radical polymerization to encapsulate cells/tissues/bioactives. (Confirmed in this session as the title associated with the '053 citation-table entry and as a related document to the '053 on the Typeset mirror of the record.)

§ 102 assessment: No anticipation. Hubbell's particle/gel is formed by photopolymerization of synthetic macromers, not by polymer-induced dehydration/volume exclusion of a macromolecule near its pI. It lacks every distinguishing '053 limitation (≥40 wt% macromolecule, pI-proximity, thermal energy source, water-soluble intertwined matrix). It is, at most, § 103 art on the generic "entrap a biomolecule in a polymer" concept — and it is not commonly owned, so § 103(c) would not disqualify it if a § 102(e) date attached. Check its filing date vs. the 1993/1994/1996 ladder before using it.

3.3 US 5,578,709 — Woiszwillo (1996-11-26) — parent AND cited reference

I retrieved the actual claim 1 of US 5,578,709 this session (EveryPatent/FreePatentsOnline), which is the single most probative document for understanding what the family protects:

"1. A method for making microparticles having uniform size comprising the steps of: a) combining a solution containing a macromolecule with a solution containing both polyvinylpyrrolidone and polyethylene glycol to produce a reaction solution; b) incubating the reaction solution at a predetermined temperature greater than room temperature for a sufficient amount of time to form microparticles; and c) separating the microparticles from the reaction solution." (claim 4 adds "pH between approximately 5 and 8"; claim 6 lists the macromolecule genus; claims 7–9 add a crosslinking agent.)

§ 102 assessment: Because '053 is a continuation of US 6,090,925, which is a CIP of 08/206,456 → US 5,578,709, no claim of '053 that is entitled to the benefit chain can be anticipated by '709: '709's effective date is not before the '053's own effective date. Where a '053 claim lacks written-description support in the 1993 '237 disclosure, '709 (issued 1996-11-26) becomes available:

• § 102(e): only if "by another" — '709 names Woiszwillo alone vs. seven inventors here, so formally yes; but the benefit chain and common ownership make this a non-starter for most claims, and § 103(c) blocks any obviousness use (common ownership by Epic/Baxter at the time of invention).
• § 102(b): would require the claim's effective filing date to be on/after 1997-11-26, i.e., only claims whose sole support is the 2000-01-14 filing. That is a narrow and, as to the particle-form claims, improbable set.

Verdict: not prior art to this patent in any realistic scenario; it is a double-patenting/terminal-disclaimer matter (consistent with the terminal disclaimer already flagged in the file history). Note the substantive point for the record: '709's claim 1 already recites the PVP+PEG / above-room-temperature / separate-the-particles method — so if a '053 method claim recites the same steps without the pI limitation, the two patents are in § 102-territory only through the priority/benefit rules, not through prior-art status.

3.4 US 6,090,925 (2000-07-18) and US 5,525,519 (~1996-06-11) — Woiszwillo family

• US 6,090,925 is the immediate parent ('053 is a continuation of it) and appears in the '053 citation table. It cannot be § 102 art — same disclosure, same § 120 chain, and its own issue date (2000-07-18) is before '053's 2000-01-14 filing only in the trivial sense that they are the same family. This is the reference that most nearly mirrors the '053 claim categories (its claim 20 "A method of making microparticles comprising combining a macromolecule and a polymer in an aqueous solution at a pH near the isoelectric point…"; claim 21 "A microparticle prepared by a method comprising…"; claim 43 "A method for delivering a therapeutic agent…" — quoted in my earlier-generated section from the '925 record). Treat as § 120 benefit, not prior art.
• US 5,525,519 (Woiszwillo) is the U.S. counterpart of WO 93/14110 and is cited in the '053 spec for polymer-preparation methods. Same analysis as § 3.1, with one difference: as a U.S. patent, it can carry a pre-AIPA § 102(e) date as of its own filing date (likely 1993-01-07, the PCT/Priority date; verify). If that filing date precedes the '053's effective date and the claim at issue lacks 1993 support, it is a live § 102(e) reference — but § 103(c) removes it from obviousness (common ownership), leaving only anticipation, which its precipitation-only disclosure cannot establish for the particle claims. [Verify the exact issue/filing dates — I did not confirm them against a primary document in this session.]

3.5 The PLGA/biodegradable-microsphere patents (rows 6–13, plus EP 248,531) — background only

Citations as cited by '053: US 5,213,812 (Ruiz); US 5,417,986 (Reid et al.); US 4,530,840 (Tice et al.); US 4,897,268 (Tice et al.); US 5,075,109 (Tice et al.); US 5,102,872 (Singh et al.); US 5,384,133 (Boyes et al.); US 5,360,610 (Tice et al.); EP 248,531 (Southern Research Institute).

Description (per the '053 text): the PLGA homopolymer/copolymer microsphere art used for controlled drug delivery, in which "the polymers form the supporting structure of these microspheres, and the drug of interest is incorporated into the polymer structure."

§ 102 assessment: No anticipation of any '053 claim category. These teach the inverse architecture of the '053: polymer-majority matrix with a small drug load. The '053 requires macromolecule ≥40 wt% and (preferably) polymer ≤30 wt%, formed without organic solvent and without a water-in-oil emulsion, at pH near pI, by energy-induced dehydration. They are directly on point only for the '053's problem statement and would be the obviousness backdrop for the goal of sustained release, not for the claimed route. They remain useful § 103 art against any '053 claim that omits the weight-percentage and pI limitations — which is why the actual claim text matters enormously here.

3.6 US 4,904,479 — Illum (block-copolymer microspheres) — best § 103 polymer-pick reference

Description: microspheres formed from block copolymers, expressly "tetronic 908 and poloxamer 407," cited by '053 for exactly that. Molten significance: '053 claims poloxamer as a usable polymer and Example 12 of '053 makes BSA microparticles using a PEG + poloxamer 407 mixture. So Illum supplies, in a single reference, the polymer species the '053 claims — but in a polymer-matrix microsphere context, not macromolecule-rich dehydration particles. Verdict: no § 102 anticipation; meaningful § 103 art for polymer-selection claims.

3.7 US 5,149,543 — Cohen et al. (polyphosphazenes)

Description: polyphosphazene microspheres/matrices for drug delivery, cited by '053 as the polyphosphazene microsphere art. Verdict: no § 102. Its polymer chemistry does not even appear in the '053's preferred polymer set (PVP, PEG, dextran, poloxamer, PVA).

3.8 US 5,422,120 — Sinil Kim (lipid/water-soluble drug encapsulation)

Description (per '053 text): "lipids arranged in bilayer membranes surrounding multiple aqueous compartments to form particles may be used to encapsulate water soluble drugs … These particles are generally greater than 10 µm in size and are designed for intraarticular, intrathecal, subcutaneous and epidural administration." The '053 also notes liposomes are "30 µm or greater."

§ 102 assessment: No anticipation. No polymer, no macromolecule-rich dehydrated matrix, wrong size regime (the '053's particles are <10 µm, typically sub-micron per Examples 2–6: 0.067–0.082 µm). Caution on drafting: if a '053 claim were broad enough to cover "a lipid-encapsulated aqueous compartment," Kim might reach it — but the '053's claim categories as summarized all require a macromolecule/polymer matrix, so this is a hypothetical.

4. Foreign patent documents that are NOT on the '053 face but ARE the family's file art

I retrieved the EP counterpart, EP 0 688 429 B1 ("Macromolecular microparticles and methods of production"; priority 1993-03-09; filed 1994-03-04; granted 1998-02-11; applicant Middlesex Sciences, Inc., proprietor Epic Therapeutics, Inc. — verified via PubChem https://pubchem.ncbi.nlm.nih.gov/patent/EP-0688429-B1 and INPI https://data.inpi.fr/brevets/EP0688429). Its background section recites the art that was considered against the family, which is the best available proxy for what the U.S. examiner saw:

The GB 2,002,319 / JP 86-223230 pairing is the combination most worth stress-testing against a broad '053 claim: one teaches PVP-mediated dehydration of a biomolecular assembly, the other teaches the PVP + PEG binary with a labile bioactive. Neither reaches the '053's particle-architecture limitations.

5. Non-patent literature cited in the '053 record

• Williams, C.A. & Chase, M.W. (eds.), METHODS IN IMMUNOLOGY AND IMMUNOCHEMISTRY, Vol. II, pp. 288–289 (Academic Press, NY 1968) — cited in '053 Examples 2 and 3 for the Anthrone free-polysaccharide assay. Pure methodology; no § 102 or § 103 relevance to the claims.
• The '709/'925 family's own NPL list (retrieved from the US5578709/US6090925 PDFs) shows the technical backdrop the family was written against — Suelter, A Practical Guide to Enzymology (Wiley 1986) pp. 78–87; Phillips et al., Biotechnol. Prog. 7:43–48 (1991); Waldmann, Science 252:1657–1662 (1991); Taylor, Genetic Engineering News (Feb. 1993) p. 5; and a review, "The controlled parenteral delivery of polypeptides and proteins." These are general knowledge references that could support a § 103 motivation argument but cannot anticipate.

6. References that cite '053 (backward view — not prior art, but shows the crowded field)

For completeness, the '053 is cited by later microparticle patents, e.g. EP 2,072 040 B1 (which summarizes it as: "US6268053 deals with microparticle comprising macromolecule (hormone, protein) and polymer, wherein the concentration of macromolecule in the microparticle is at least 40% and less than 100% by weight. Polymers include polyvinylpyrrolidone, polyethylene glycol, dextran, nonylphenol ethoxylates, polyvinyl alcohol." — an independent third-party characterization of the '053's inventive core, and it aligns exactly with the ≥40 wt% limitation), and the RU 2,457,854 C2, US 10,821,185, US 8,309,129, US 8,073,591, US 8,709,827 and US 7,094,369 citation tables. None of these is prior art to '053.

7. Anticipation verdict — bottom line

1. No reference on or around the '053 record is a clean § 102 anticipatory reference to the patent's distinguishing claims. The examined field (PLGA microspheres, liposomes, polyphosphazenes, block-copolymer microspheres, polymer-wall microcapsules, surface-conjugated carrier particles) does not disclose the '053's combination of: (a) a macromolecule-polymer microparticle in which the macromolecule is 40–<100 wt% and polymer ≤30 wt%; (b) formation by volume exclusion / dehydration with a soluble polymer at a pH within ~1.5–4 units of the macromolecule's pI; (c) an energy source (heat) rather than organic solvent, emulsion, or crosslinker as the particle-forming trigger; and (d) the resulting water-permeable, water-soluble intertwined matrix giving sustained, burst-free release.
2. The only genuinely dangerous § 102 reference is WO 93/14110 / US 5,525,519 (Woiszwillo) — and only (i) against claims lacking 1993/1994 support, and (ii) only if such a claim is drafted broadly enough to read on macromolecule precipitation with a linear polymer or on a corresponding kit. Its 1993-07-22 publication date, its same-inventor authorship, and the § 102(b)/§ 103(c) mechanics make this a priority- and claim-drafting-dependent attack, not a straightforward one.
3. The Woiszwillo family patents (5,578,709; 6,090,925; 5,525,519) are benefit-chain/double-patenting references, not § 102 prior art, for any claim entitled to the 1993-03-09 chain. US 5,578,709 becomes available only for claims whose sole support is the 2000-01-14 filing — an improbable set.
4. Everything else is § 103 material at best, and the most probative combinations are: GB 2,002,319 + JP 86-223230 (PVP dehydration + PVP/PEG with a bioactive); WO 93/14110 + any heat-incubation teaching; Illum (US 4,904,479) + the PVP/PEG teaching for the polymer-selection claims; and the Tice/Ruiz/Reid/Singh/Boyes PLGA cluster for the sustained-release purpose.

8. Claim-mapping matrix — to be completed against the granted claims

Do not treat the left column as verified claim numbers. These are the claim categories the specification supports. Fill in the numbers from the printed patent / USPTO PatentCenter.

9. What I could not verify — pull these before relying on the above

1. The granted claim set of US 6,268,053 — absent from the authoritative text supplied; get it from USPTO PatentCenter or the printed patent. Every anticipation conclusion above is category-level until then.
2. The complete PTO-892 / IDS list on the '053 face — I confirmed only US 5,567,435, US 5,578,709 and US 6,090,925 from third-party citation tables. A full on-face list may add references I have not analyzed.
3. Exact dates for rows 6–17 (US 4,530,840; 4,897,268; 4,904,479; 5,075,109; 5,102,872; 5,149,543; 5,213,812; 5,360,610; 5,384,133; 5,417,986; 5,422,120; 5,525,519 and EP 248,531) — I flagged them [S] rather than [V] because I did not confirm each against a primary document in this session.
4. The '053 file wrapper's priority determination — whether the examiner made any express finding on which claims get 1993 versus 1996 support. This controls the entire § 102(b) analysis and is worth pulling from PatentCenter's IFW.

No case, reference, date, or claim number above has been invented. Where the record was unavailable, I have said so and marked it.

I'll research the prior art references cited in this patent and attempt to recover the actual claim text before building the obviousness analysis.

Let me recover the claim set and characterize the key cited references.

Obviousness Analysis — US 6,268,053 B1 under 35 U.S.C. § 103

Analyst note on scope and epistemics. Two constraints shaped this analysis, and I state them up front rather than burying them:

1. The claim set is still not in the authoritative text supplied to me. As flagged in the earlier sections of this analysis, the full text provided for US 6,268,053 ends inside the "Detailed Description"; the claims section is absent. Everything below about claim categories is therefore built from (a) the '053 specification's own statements of invention, (b) the recovered claims of the closely related family members US 5,578,709 and US 5,981,719, and (c) the classification profile. I will not attribute a specific claim number or verbatim claim language to '053 unless the source is the family member that actually carries it. Any claim-level conclusion here should be re-run against the granted claim set from USPTO Patent Center.
2. The "Prior Art" I was asked to use is the set of references appearing on the '053 record — principally the Background-of-the-Invention citations reproduced in the authoritative text, plus the Woiszwillo family members that the '053 specification expressly incorporates. I verified these against primary documents where I could and cite them.

Practical caveat before the merits: the patent expired 2013-03-09 ("Expired – Lifetime," https://patents.google.com/patent/US6268053/en). A § 103 analysis of an expired patent is a retrospective validity exercise (e.g., for a § 282 defense, or a collateral estoppel fight), not a prosecution strategy. That framing matters because the reason the office allowed the claims and what a challenger must now prove are different questions.

1. Governing framework (pre-AIA § 103)

US 6,268,053 is a pre-AIA patent. Its claims trace to application 08/028,237, filed March 9, 1993. The statutory test is therefore the pre-AIA § 103(a) formulation as elaborated in Graham v. John Deere, 383 U.S. 1 (1966), and KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007):

• Scope and content of the prior art, differences between the prior art and the claims, and level of ordinary skill;
• Whether the differences would have been obvious — with any articulated reason having a rational basis, including "combining prior art elements according to known methods to yield predictable results," "simple substitution of one known element for another," "use of a known technique to improve similar devices in the same way," and "obvious to try" among "a finite number of identified, predictable solutions."
• Objective indicia (secondary considerations) must be considered if applicant puts them in issue.

Two pre-AIA doctrines do real work here:

(a) Effective filing date per limitation. Under 35 U.S.C. § 120, a continuation/renewal gets the parent's date only for subject matter the parent supports. The '053 chain is 1993-03-09 ('237, abandoned) → 1994-03-04 ('709) → 1996-08-19 ('925) → 2000-01-14 ('053). Measured textually, the "at least 40% and less than 100% ... macromolecule" / "polymer less than 30% by weight" limitations do not appear in the recovered US 5,578,709 disclosure or claims (compare https://patentimages.storage.googleapis.com/47/10/f0/937851161edfe9/US5578709.pdf and the '709 claim text at https://FreePatentsOnline.com/[5578709](/patent/5578709).html), but they do appear verbatim in the '925 specification (https://patentimages.storage.googleapis.com/dc/5a/15/96bb1380387276/[US6090925](/patent/US6090925).pdf). That is a strong textual signal that those limitations carry a 1996-08-19 effective date, not 1993-03-09. A challenger should brief this — it materially expands the prior art. I flag it as an inference from document comparison, not a legal conclusion; it requires a § 120 written-description analysis of the '237 and '709 disclosures.

(b) Common ownership / § 103(c). The closest art — US 5,525,519; US 5,554,730; US 5,578,709; and WO 93/14110 — is the Woiszwillo/Epic (formerly Middlesex Sciences) family. Pre-AIA § 103(c) disqualifies subject matter "developed by another person" that qualifies only under § 102(e)/(f)/(g), where the subject matter and the claimed invention were commonly owned at the time the invention was made. Because the same inventive entity and assignee run through the family, these references cannot be used as § 103 combinable art for the overlapping subject matter. Importantly, however, § 103(c) does not reach § 102(b) art, so if the 40%/30% limitations get a 1996 effective date, WO 93/14110 (published 1993-07-22) becomes available as a § 102(b) reference against those limitations notwithstanding common ownership. This is the single most consequential doctrinal hinge in the analysis.

2. The prior-art universe actually on the '053 record

Drawn from the '053 Background section (authoritative text) and the family documents:

3. Element-by-element mapping of the likely independent claims

Using the '053 specification's own statement of the invention and the near-identical '925 claim format (method-of-making; microparticle; method-of-delivery), the independent claims almost certainly reduce to three families. Mapping each element to the art:

Claim family A — Method of making

Combine a macromolecule and a soluble polymer in aqueous solution at a pH near the macromolecule's isoelectric point; expose the mixture to an energy source for a predetermined time; recover the microparticles.

Assessment: Absent the § 103(c) bar, '709 in view of the isoelectric-precipitation principle is a prima facie § 103 case. The only element '709 does not textually recite is "pH near the pI," and that gap is bridgeable by the single most standard concept in protein purification. Note the '053 specification itself concedes the tolerance is broad — "preferably within 3 to 4 pH units of the pI … most preferably within 1.5 to 2 pH units" — which is a range, and broad ranges supported only by a general principle are classic obviousness territory. The real fight is § 103(c), not the technical merits.

Claim family B — The microparticle composition

A microparticle comprising a matrix of substantially homogeneously distributed, intertwined macromolecule and polymer, wherein the macromolecule is ≥40% and <100% by weight and the polymer ≤30% by weight; the particle being permeable to water.

Assessment: This is the weakest of the three families for a challenger and the strongest for the patentee, for two reasons. First, the weight ratio is a numerical limitation that is the stated point of novelty — the '053 Background attacks PLGA microspheres precisely because they "exhibit a poor loading efficiency and are often only able to incorporate a small percentage of the drug," and the specification then inverts the paradigm (macromolecule is the majority component). Second, inverting the majority/minority relationship in a composite is exactly the kind of change a patentee can argue was counterintuitive at the time. A challenger needs an explicit teaching or suggestion of macromolecule-majority loading, or a strong "result-effective variable / finite predictable solutions" showing under KSR. Tabata (a protein/polymer matrix at elevated temperature) plus the '053 Background's own admission of the loading problem gets a challenger close — but the § 103(c) problem with '709 remains the cleanest attack.

Claim family C — Method of use / delivery

Delivering a therapeutic (or detecting a target) by administering the macromolecule-rich microparticles.

Assessment: Highly vulnerable. Once a water-permeable, sustained-release, injectable particle exists, using it to deliver a therapeutic is the enumerated use of the entire field. Illum US 4,904,479 (intravenous targeting with coated sub-micron colloids), Kim US 5,422,120 (parenteral particulate delivery), and the Tice family (sustained release) collectively supply the motivation; the '053 specification's own list of cargoes (leuprolide, nafarelin, insulin, LHRH, doxorubicin) maps onto drugs already delivered by PLGA microspheres. Under KSR, "the improvement of one reference by the addition of another reference's known function" is squarely obvious.

4. Specific combinations and the motivation to combine

Below I pair references and state the rational basis a challenger would articulate. I flag where a reference's use is barred or complicated by § 103(c) / priority.

Combination 1 — Woiszwillo '709 + isoelectric-precipitation principle (+ '730 for the dehydration mechanism)

• Teachings combined: '709's aqueous PVP/PEG macromolecule incubation with the standard protein-chemistry rule that protein solubility (and hence spontaneous aggregation) is maximized near the pI.
• Motivation (multiple, independent):
  1. Known technique to improve a similar process in the same way. Adjusting pH to the pI is the single most common way to drive protein out of solution; a POSA optimizing '709's "pH 5–8" window would inevitably titrate toward the protein's pI to improve yield — and the '053 specification's own claim that incubation conditions are "optimized to incorporate approximately 100% of the macromolecule" confirms yield was the recognized figure of merit.
  2. Predictable result. The claimed outcome (particle formation) is what isoelectric precipitation is known to produce; heat supplies the denaturation/annealing step already claimed in '709.
  3. '730 supplies the explicit mechanistic bridge ("macromolecular crowding agent" → volume exclusion), confirming the POSA understood why soluble polymers drive macromolecule self-association.
• § 103(c) caution: '709, '519, '730 and WO 93/14110 are the patentee's own commonly owned family. If the claims get the 1993-03-09 date, or if the common-ownership relationship is intact at the time of invention, these references are disqualified as § 103 art for the overlapping subject matter. The isoelectric-precipitation teaching itself, however, is non-family art (general protein chemistry) and remains available.

Combination 2 — PLGA/organic-solvent art (Tice '840/'268/'109/'610; Ruiz '812; Reid '986; Singh '872; Boyes '133; EP 248,531) + the Woiszwillo aqueous/volume-exclusion art

• Teachings combined: The polymer-matrix microsphere art defines the problem (sustained parenteral delivery) and its failure modes (organic solvents risking denaturation and residual toxicity; large, aggregating particles; burst release), while the Woiszwillo art supplies the aqueous, polymer-dehydration alternative.
• Motivation: The '053 Background itself articulates the rational basis: residual organic solvents "could be toxic when administered to humans or animals," could "denature proteins or peptides," and required "special facilities … to handle organic solvents." KSR makes an express statement of the problem in the specification fair game as a design incentive. A POSA seeking an injectable, protein-compatible microsphere had a finite, identified set of solutions, and polymer-induced volume exclusion in water was one of them.

Combination 3 — Tabata (1993) + Gombotz '400 + Wise (1984) + a heat-annealing step

• Teachings combined: Tabata teaches protein/polymer matrix particles (trypsin, insulin in PLA) formed by elevated-temperature neat mixing; Gombotz teaches atomize-and-freeze protein/polymer microspheres; Wise teaches matrix comminution. Each teaches that the protein can be a substantial fraction of a polymer matrix.
• Motivation/bridge to the 40 wt% limitation: Tabata expressly identifies the two problems the '053 patent claims as its advantage — ~10% protein activity loss and a "large initial burst" of release. Combining Tabata's protein-rich matrix concept with an aqueous, non-solvent route directly targets both. This is the strongest available route to the ≥40 wt% / ≤30 wt% limitation, and Tabata/Gombotz/Wise are third-party art not subject to § 103(c).
• Priority note: Tabata is a 1993 publication. If the 40%/30% limitations carry the 1996-08-19 date (see § 1(a)), Tabata is comfortably § 102(b) art against them. This combination is the one I would lead with.

Combination 4 — Illum US 4,904,479 + Kim US 5,422,120 + the particle art

• Teachings combined: Illum teaches surface-coating sub-micron colloids with PEG-containing block copolymers (poloxamer 407, poloxamine 908) and injecting them intravenously to control biodistribution — the '053 specification's own "coat/decorate to facilitate targeting, enhance receptor mediation, and provide escape from endocytosis" concept. Kim establishes that parenteral particulate delivery is an accepted modality.
• Motivation: Once the microparticle of Combination 1–3 exists, using it for targeted/sustained delivery is the field's raison d'être; the '053 method-of-use claims add nothing beyond the conventional use of a known delivery vehicle. This combination chiefly targets claim family C (methods of use), where it is strongest.

Combination 5 — '730 (macromolecular crowding) + the nucleic-acid/cation art, for the nucleic-acid microparticle claims

• Teachings combined: '730's crowding-agent route to polysaccharide–protein conjugate microparticles, extended to nucleic acids. The '053 specification itself states nucleic acids "are preferably prepared by first mixing the nucleic acid either with a protein, such as bovine serum albumin, or … the addition of a cation, such as polylysine."
• Motivation: Charge neutralization to condense polyanions is standard; complexing DNA with polycation (polylysine) or with a carrier protein for particle formation was a known approach in the gene-delivery literature by the mid-1990s.
• Honesty flag: I did not verify the specific polylysine–DNA references (e.g., Wu & Wu; Felgner) in this session, and they do not appear among the '053 Background citations I was given. I flag them as art a challenger would need to develop independently, not as demonstrated record art.

5. Anticipated patentee rebuttals (and how strong they are)

1. § 103(c) / common ownership. As discussed — the closest technical art is the same family. This is the patentee's best defense, and it could force a challenger onto the third-party art (Tabata, Gombotz, Illum, Tice), which teaches the goal and adjacent structures but less cleanly the exact aqueous near-pI process.

2. Unexpected results / inversion of the paradigm. The patentee will argue that making the macromolecule the majority component (≥40 wt%) with polymer ≤30 wt% was counterintuitive when the entire PLGA field put the polymer as the structural matrix. If the '053 examples (FIGs. 1–6 release data; the "no initial burst" assertion) can be tied to the claimed ratio, this is a cognizable Graham factor. Its weakness: the specification also asserts the ratio can be reached by routine manipulation — "the characteristics of the microparticles may be manipulated during preparation by adjusting the type of polymer, polymer concentration, … incubation temperature, pH, macromolecule concentration" — which reads as an invitation to routine optimization rather than a surprise result.

3. Retention of bioactivity / avoidance of burst. The patentee will tie these to the aqueous, organic-solvent-free route. Counter: the '053 specification itself says the process "is mild and does not adversely affect the biological activity" and that release can be tuned, but it does not quantify a result that the prior art (Tabata's 10% loss, burst) would have predicted could not be avoided. Burst avoidance and activity retention are exactly the design goals Tabata put in the art.

4. Teaching away. Kim '120 (lipid particles >10 µm for intraarticular/intrathecal/epidural) and the PLGA art's "large, aggregating" particles could be argued to steer away from sub-10 µm aqueous particles — but they steer toward large particles, not away from the '053 process, so the doctrine is weakly positioned. There is no clean teaching-away reference in the cited set.

6. Bottom line

My single most important recommendation: before relying on any of this, resolve the § 120 effective-filing-date question for the "≥40%/<100% macromolecule" and "≤30% polymer" limitations by comparing the '237 and '709 disclosures against the '925 text. My document comparison indicates those limitations appear first in the 1996-08-19 '925 filing, not the 1993-'237 filing — which, if confirmed, makes WO 93/14110 (pub. 1993-07-22) and Tabata (1993) available as § 102(b) art against the very limitations that carry the novelty weight, and simultaneously defeats the § 103(c) common-ownership shield for that art (since § 103(c) does not reach § 102(b) references). That single finding, more than any technical argument, would decide the obviousness question.

Confidence and limits. I am confident in the content of the references I quoted (they came from the primary documents linked above). I am not confident in the verbatim text of any '053 claim, because the granted claims were not in the source text and I did not fabricate them; the "claim families" above are labeled inference. I also did not verify the Tabata publication month (only the volume/year and its characterization inside WO 97/42940), and I did not verify any specific pre-1996 polylysine–DNA reference. Those items should be pulled and confirmed before this analysis is used in a validity contention.