US 5601844

I'll run searches to check for any USPTO records and any 2026 CAFC docket activity involving this exact patent number.

Let me run a couple of targeted checks on litigation/docket activity and UPC/PTAB records.

US 5,601,844 — Verification and Summary

Docket/litigation check (as requested): I searched for any 2026 CAFC docket activity and any USPTO post-grant or district court record tied to the exact number 5,601,844. I found none. Every "844 patent" hit in those searches referred to different patents — e.g., 6,154,844 (Finjan), 8,624,844 (LiTL), 8,332,844, 9,526,844, and 8,013,884 (mislabeled in one court document) — not 5,601,844. Likewise, "5601844" appears in soybean SNP marker names (e.g., BARC_1_01_Gm07_5601844_G_A), a false positive I excluded. Caveat: I cannot directly query PACER or the CAFC's internal docket system, so I cannot rule out a filing that is not web-indexed; but on the available evidence there is no 2026 appellate activity for this patent. That is expected — the patent expired 2014-02-11 ("Expired – Lifetime"), roughly 12 years ago.

Bibliographic data (per the authoritative full text)

Sources: Google Patents US5601844A; Justia US5601844.

Abstract (as issued)

A sustained-release preparation made by enclosing a macrocyclic tricyclo compound — specifically 17-allyl-1,14-dihydroxy-12-[2-(4-hydroxy-3-methoxycyclohexyl)-1-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0⁴,⁹]octacos-18-ene-2,3,10,16-tetraone (i.e., FK506/tacrolimus) or its 17-ethyl analog — into fine particles generally called microspheres made of biodegradable polymer. When given by injection, the preparation appreciably improves transfer of the macrocyclic compound into the blood, and it is also suitable for topical administration.

Plain-language overview of the claims

Claim 1 (the only independent claim) — A sustained-release medicine made by encapsulating:

1. a tricyclo compound of formula (I) (a large macrocyclic lactone, the definition of which is then spelled out across ~15 substituent variables R¹–R²³, X, Y, and n) or a pharmaceutically acceptable salt of it,
2. inside fine microspheres whose matrix is a pharmaceutically acceptable biodegradable polymer, narrowed to a three-member Markush group: polylactic acid (PLA), lactic acid–glycolic acid copolymer (PLGA), and mixtures of those.

The compound definition is broad on its face, but every subsequent claim narrows it toward the FK506 family.

Claim 2 — Narrows the compound: R³/R⁴ and R⁵/R⁶ may form a double bond; R⁸ and R²³ are H; R⁹ is OH; R¹⁰ is methyl, ethyl, propyl or allyl; X is (H,H) or oxo; Y is oxo; R¹⁴–R¹⁹ and R²² are all methyl; R²⁰/R²¹ are each (substituent, H) where the substituent is hydroxy, alkyloxy, or (for R²¹ᵃ) protected hydroxy; n is 1 or 2.

Claim 3 — Adds R⁷ = H, OH or protected hydroxy; X = oxo; R²⁰ᵃ = methoxy; R²¹ᵃ = hydroxy or protected hydroxy.

Claim 4 — Narrows the compound to the single named species: 17-allyl-1,14-dihydroxy-12-[2-(4-hydroxy-3-methoxycyclohexyl)-1-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0⁴,⁹]octacos-18-ene-2,3,10,16-tetraone (FK506 / tacrolimus). Notably, this is the claim most likely to have had commercial significance.

Claim 5 — The tricyclo compound is present at 0.01–50 weight % of the microspheres (specification prefers 0.1–20 wt%).

Claim 6 — The microspheres are 200 μm or less in size (i.e., small enough to pass an injection needle).

Claim 7 — The preparation is adapted for intraarticular injection (the specification also lists intramuscular injection, other injections, ocular instillation, inhalation, oral, and rectal routes).

Disclosure highlights (for context)

• The specification states that microspheres of biodegradable polymer were themselves known, but that enclosing the macrocyclic compound (I) in microspheres "remains unknown up to now," including whether it could be formulated at all or would show sustained release.
• Worked example: FK506 (0.05 g) + methylene chloride (2, 4, or 8 mL) + PLGA (0.5 g), emulsified into 1% gelatin solution at 6 °C × 5000 rpm × 5 min, solvent removed, filtered, centrifuged, washed and freeze-dried. Resulting particle sizes: 37.3 μm (2 mL), 16.1 μm (4 mL), 7.5 μm (8 mL) — showing size decreases with more organic solvent.
• In vivo data: 16.1 μm particles given to rats by intraarticular injection at 2 mg/kg, with whole-blood FK506 concentration plotted in FIG. 1 (log scale), said to demonstrate sustained release over a very long period.
• The specification expressly contemplates cyclosporins or rapamycins as alternative active ingredients, and cites a long list of related EP/GB/JP applications (e.g., EP-A-353678, EP-A-413532, GB 2225576.A).

Prior art cited on the face of the patent

EP0323042A1 (Fisons), US4916138A (Fujisawa — solid dispersion of FR-900506), EP0484936A1 (Fujisawa — suspensions of tricyclic compounds), US5196437A (Fujisawa — FK506 for hepatic disease/liver regeneration), US5260301A (Fujisawa — FK506 solution), US5385907A (Fujisawa — FK506 ointments).

Uncertainty / limitations of this report

• Bibliographic fields and claim text above come from the authoritative full patent text; I regard them as reliable.
• Assignee status is reported literally as listed by the source and is not a legal conclusion. The record shows two reassignments (1995 to Fujisawa Pharmaceutical Co., Ltd.; 2005 to Astellas Pharma Inc., described as "formerly Yamanouchi Pharmaceutical Co., Ltd.") — that parenthetical is quoted as recorded and is somewhat internally inconsistent with the stated Fujisawa merger basis, so I flag it rather than resolve it.
• I could not confirm or deny any specific 2026 CAFC docket for this patent; no such record surfaced, and the patent's 2014 expiration makes 2026 appellate activity on validity/infringement of this patent unlikely absent an unusual delayed proceeding.
• Note the OCR-visible typos in the source (e.g., "arc made of biodegradable polymer," "alkali methal," "crythcmatosus") are reproduced in the source documents, not introduced here.

I'll search for litigation involving US patent 5601844 across patent litigation databases.

Initial searches didn't surface litigation. Let me query the litigation-specific portals and databases directly.

Litigation Search: US Patent 5,601,844

Bottom line

I found no litigation — no district court case, ITC action, or PTAB proceeding — asserting or involving U.S. Patent No. 5,601,844. Based on the sources searched, no plaintiff, defendant, case number, or filing date can be reported for this specific patent.

What I searched

• General web searches on "5601844 litigation," "5601844 patent lawsuit," and "5,601,844" case docket infringement
• The Unified Patents litigation portal URL (portal.unifiedpatents.com/litigation/caselist) — no indexed result referencing 5,601,844
• CAFC opinions/orders — nothing referencing 5,601,844 (searches returned only unrelated cases, e.g., the IdeaHub v. Unified Patents Rule 36 judgment, 2024-1684)
• Google Patents and Justia pages for US 5,601,844

Important caveat on a superficially related hit

A search surfaced an Astellas press release (Oct. 28, 2010) about Astellas Pharma Inc. and Astellas US LLC v. Nycomed US Inc., filed in the U.S. District Court for the District of New Jersey on October 27, 2010, over Nycomed's ANDA for generic 0.1% tacrolimus ointment (Protopic®).

That case did NOT involve US 5,601,844. The press release states the asserted patents were U.S. Patent Nos. 5,665,727 and 5,385,907. I am flagging it only because 5,601,844 shares the same original assignee (Fujisawa Pharmaceutical Co., Ltd., now Astellas Pharma Inc.) and the same FK506/tacrolimus active-ingredient family. It is not litigation over 5,601,844, and I am not attributing it to this patent.

Why this outcome is plausible

• The patent is Expired – Lifetime, with an anticipated expiration date of 2014-02-11 (per the Google Patents status data). Its enforceable term ended roughly 12 years ago, which reduces the likelihood of a contemporaneous, indexed infringement suit.
• The disclosed subject matter is a formulation/vehicle patent (microspheres of PLA/PLGA enclosing a tricyclo (FK506-type) compound), filed 1993-11-11 with a priority date of 1992-11-18 — the era before routine electronic docketing of every case in freely searchable databases.
• Google Patents shows a full "Cited By / Citations" table for US 5,601,844 but no litigation section, which is consistent with no litigation being recorded there.

Confidence and limits

• Confidence that no litigation is publicly indexed: moderately high for the period covered by searchable databases (~2000s onward), and high that nothing is recorded on the sources I reached.
• Caveat: I could not directly query PACER (paid, no public full-text search) or run a proprietary Docket Navigator / Lex Machina search, and the Unified Patents portal did not return a direct record. Pre-2000s suits, especially in smaller venues, may not be captured by any of the free sources I used. I do not have high-confidence knowledge of any such case, and I will not fabricate one.

Conclusion: On the available record, there is no known litigation involving US 5,601,844. If you need PACER-level certainty, a manual PACER "Patent Litigation" or Docket Navigator query on the exact number 5,601,844 would be the appropriate next step.

I'll start by verifying the canonical (empty) list against public sources.

Let me run more targeted searches to be thorough before concluding.

One more check: whether the family member faced EPO opposition, and any litigation/defensive-aggregator activity.

Sourcing note

Canonical list = the "PTAB proceedings on file" block: zero AIA trial proceedings. I ran independent web checks (PTAB petition documents, PTAB/CAFC commentary, family-member registers, litigation mentions) to see whether anything surfaced that ODP has not yet indexed. Nothing did. I also found no Federal Circuit appeal, because there is no FWD to appeal.

One important caveat for a defendant running their own searches: the results are polluted by number collisions on "844." The PTAB documents that surface are about unrelated patents — US 8,284,844 ("Video Decoding System Supporting Multiple Standards," Broadcom, e.g. IPR2017-01111), US 8,624,844 (LiTL LLC, IPR2024-00404), and the Sanofi US 9,526,844 (IPR2019-01022). None of these is US 5,601,844. Do not let a vendor's docket report conflate them.

Proceedings overview

Total AIA trial proceedings on US 5,601,844: 0 — 0 active, 0 claims invalidated, 0 claims sustained, 0 settled, 0 institution denials; the patent was never challenged at the PTAB. The bottom-line defensive posture is therefore not "hardened by surviving IPRs" (that framing assumes a fight that never happened) — it is "the patent is expired and nobody bothered, because it is not worth attacking." All seven claims stand exactly as granted, untested, but the patent reached its anticipated expiration on 2014-02-11 ("Anticipated expiration," structured data; status "Expired - Lifetime"). A defendant facing a demand letter today is looking at a paper tiger: no live infringement is possible, and even pre-expiration damages are almost certainly time-barred (see Strategic summary).

Near-misses I checked and ruled out (not proceedings on this patent)

• US 8,284,844 / US 8,624,844 / US 9,526,844 — different patents, different technologies (video decoding; laptop convertibles; drug-delivery devices). Ruled out by publication number.
• EP0669127B1 (the EP family member, "Prolonged-action pharmaceutical preparation," granted 1999-08-11) — I found no evidence of an EPO opposition in the registers I could reach. The registers instead show lapse: EP96924826/EP93924826 recorded as lapsed, with the NL register listing "Lapsed by non-payment of annual fee," last annual fee paid 2009-11-14 and expiration 2013-11-11/10; the LU register lists expiration 2013-11-11. I could not confirm an opposition either way from the sources checked — treat "no EPO opposition" as unverified, not established.
• US 5,911,049 ("Osteogenic promoting pharmaceutical composition," Takeda) cites this family but is not a challenge to it.
• Prosecution-cited art (from the patent's own citation list, i.e. examiner-cited, not petitioner-cited): EP0323042A1 (Fisons), US4916138 (Fujisawa solid dispersion), EP0484936A1 (Fujisawa suspensions), US5196437, US5260301, US5385907, JPS63122620A (polylactic acid microspheres), CA2012978C, JPH0449232A.

No proceeding entries follow, because there are none to describe — I will not manufacture IPR numbers, panels, or dispositions.

Strategic summary

Claim status. All of claims 1–7 of US 5,601,844 are SUSTAINED in the sense that standing, never-touched, valid-as-issued: claim 1 (the genus claim to a tricyclo compound of formula (I) enclosed in PLA/PLGA microspheres), claim 2 (species/Markush narrowing), claim 3 (substituent definition, R²⁰ᵃ = methoxy, R²¹ᵃ = hydroxy), claim 4 (17-allyl-...-tetraone, i.e. FK506/tacrolimus), claim 5 (0.01–50 wt% loading), claim 6 (⩽200 µm particles), claim 7 (adapted for intraarticular injection). CANCELED: none. UNTESTED: all. There is no IPR certificate, no reexamination certificate, no disclaimer, and no certificate of correction visible in the material provided — so the claims have never been narrowed by any post-grant proceeding. That cuts both ways: no claim has been killed, but the patent owner has also never had its claim construction or validity validated by the Board. Given the 1993 filing date, claim 1's genus is broad, and the specification's central admission is candid — "the technique of enclosing the compound (I) ... into microspheres remains unknown up to now" (Best Mode section) — which is precisely the kind of statement that makes a § 103 case built on the JPS63122620A polylactic-acid-microsphere art plus the Fujisawa FK506 references look plausible. It was simply never tested, most likely because the economics never justified it.

Estoppel landscape. Because no IPR/PGR was ever instituted, 35 U.S.C. § 315(e)(2) estoppel is a non-issue here — there is no petitioner, no privity chain, and no bar on any ground. Symmetrically, a defendant today has no PTAB-frozen record to inherit: every art ground (JPS63122620A microspheres; EP0323042A1/Fisons; US4916138 and EP0484936A1 Fujisawa; the WPI/Derwent AN 92-102775 abstract of JP 4-49232; plus post-1997 formulation art such as the Takeda microcapsule work) is legally available. It just isn't worth using, because of the expiration and damages analysis below. Note also two statutory unavailability rules for this patent: PGR is unavailable (its effective filing date of 1992-11-18 precedes the 2013-03-16 first-inventor-to-file cutoff, and the claims are not within any enumerated PGR-eligible category), and CBM is unavailable (the patent is directed to a pharmaceutical formulation, not a "financial product or service," and the CBM transitional program sunset on 2020-09-16). So the only AIA vehicle ever available was IPR — and none was filed.

Pattern signals. No serial-petitioner pattern (0 petitions by anyone). No defensive aggregator in the chain — no Unified Patents, RPX, or similar as petitioner or real party in interest appears anywhere in the record. Astellas/Fujisawa has not pursued PTAB appeals on this patent because there were none to pursue; its appellate activity on the broader tacrolimus portfolio is a separate question I did not verify. The strongest signal is negative and structural: the patent issued in 1997, had 17 years of enforceable life during which tacrolimus microsphere/depot formulation was a commercially active space, and attracted zero post-grant challenges. That is consistent with a patent that practitioners judged as having limited independent value over the underlying FK506 compound art rather than one that scared competitors off.

The real kill-shot (independent of PTAB). The patent expired 2014-02-11. Under 35 U.S.C. § 286, no recovery lies for infringement more than six years before a complaint is filed. Any complaint filed on or about 2026-09-30 could reach only conduct after roughly 2020-09-30 — and there can be no infringing conduct after expiration. Practically, therefore, the '844 patent cannot support a damages case against anyone now, absent a rare tolling theory (e.g., fraudulent concealment) that would need to be pleaded with particularity and that I have no evidence for. Confirm the fee/expiration status and any terminal disclaimer or withdrawal of an extension in USPTO Patent Center before relying on that conclusion; § 286 tolling is fact-specific.

Recommended next steps

1. If you are a defendant and received a demand letter citing US 5,601,844 (or its EP/JP/CN/AU family members): the correct response is not an IPR petition — it is a standing/expiration and § 286 letter. There is no FWD to link to, because none exists; link instead to the patent record showing expiry and status, e.g. https://patents.google.com/patent/US5601844/en (the authoritative source used here, showing "Anticipated expiration 2014-02-11" and "Expired - Lifetime"). Note the family is in the same posture: WO1994010981A1 (ceased), EP0669127B1 (lapsed), JP3520517B2 (expired — fee related), AU5434094A (abandoned), DE69326015T2 / ES2134860T3 / DK0669127T3 (expired). Verify each of those in its national register before asserting it in correspondence.
2. Do not file an IPR to get a "clean" win. It would be expensive, would likely be denied or dismissed as moot given expiration and no live controversy, and buys nothing you don't already have. If you nonetheless need a merits record (e.g., a customer indemnity demand), commission a validity opinion memo rather than a petition.
3. Run one confirmation pass in the official systems before you take a position: PTAB E2E / PTAB Center patent search for 5,601,844 (https://ptact.uspto.gov — or the legacy PTAB E2E at https://ptacts.uspto.gov/ptabweb/) and USPTO Patent Center for the maintenance-fee/expiration record; plus the EPO Register and the UK IPO journal entry for EP0669127 if your exposure is European. The ODP "no proceedings" result is the canonical list, but a fresh E2E search is cheap insurance.
4. If instead you are the patent owner or an assignee: the absence of any PTAB activity is not reassuring about value. The patent expired 12 years ago, its EP counterpart lapsed for non-payment of an annuity (last payment 2009-11-14 per the NL register), and the broad genus claim 1 rests on a specification that admits the microsphere-enclosure technique was previously unknown. Licensing revenue from this family today should be underwritten at approximately zero.
5. Timeline milestones: none to track — there is no institution decision deadline, no oral hearing, and no statutory one-year FWD due date, because no trial was ever instituted.

Confidence and limits. High confidence that no AIA trial proceeding exists on US 5,601,844: the structured ODP block says so, and multiple independent searches returned nothing while surfacing only same-number-different-patent artifacts. Lower confidence on two points I could not fully exhaust: (a) whether an EPO opposition was filed against EP0669127B1 in the 1999–2000 window (not found, but I could not reach a definitive EPO Register opposition tab in the material retrieved), and (b) whether the patent was ever asserted in district court litigation (my final litigation-specific search call was cut off by a step limit). Neither affects the PTAB count, and neither would change the expiration/§ 286 conclusion.

I'll research the assignment record for US 5601844 before drafting. Let me run several targeted searches.

Let me check for any litigation or NPE assertions tied to this specific patent number.

Assignment Record Analysis — US 5601844 ("Sustained release medicinal preparation")

Source and access note (read first). I could not load the USPTO Assignment Center record (https://assignmentcenter.uspto.gov/) directly, and my searches did not surface any published reel/frame number or correspondent of record for this patent. The assignment data below is taken from the Google Patents legal-events feed for US 5601844 (https://patents.google.com/patent/US5601844/en), which mirrors the underlying USPTO assignment records but does not expose reel/frame or correspondent fields. I have therefore not fabricated reel/frame numbers. Where a field was unavailable, I say so explicitly. Verify against https://assignment.uspto.gov/patent/index.html (search "5601844") before relying on any of this for a filing.

Inventors

Five named inventors, all listed on the 1995-08-02 assignment of assignors' interest to Fujisawa:

• Akira Kagayama
• Sumihisa Kimura
• Saburo Murata
• Sachiyo Tanimoto
• Takehisa Hata

Employer at filing: Presumed Fujisawa Pharmaceutical Co., Ltd. (Osaka) — they are the assignors of record and the original assignee was Fujisawa; the patent text gives no inventor addresses and I did not independently verify individual employment. No departure data was found for any inventor, so I cannot confirm or refute the "all inventors departed within 12 months" pattern. This is a common corporate research-lab inventorship roster with no unusual features.

Original assignee

Fujisawa Pharmaceutical Co., Ltd. (Osaka, Japan; founded 1894).

• Primary line of business: Research-based ethical pharmaceuticals — manufacturing, marketing and import/export of prescription drugs.
• Product embodying the claims: Unclear. The claimed subject matter is a sustained-release microsphere formulation of the macrolide FK506 (tacrolimus). Fujisawa did commercialize tacrolimus as Prograf (immediate-release oral/IV), but the patent's own working example is only a rat intraarticular pharmacokinetic study (FIG. 1) — no human or commercial microsphere product is evidenced in the specification. I found no evidence that the specific claimed microsphere dosage form was ever marketed.
• Current status: Acquired / dissolved by merger. Fujisawa merged with Yamanouchi Pharmaceutical Co., Ltd. effective 2005-04-01; Yamanouchi was the surviving entity and was renamed Astellas Pharma Inc., with Fujisawa dissolved (Astellas press release, 2004-05-24, and the Astellas 2005 merger announcement). The current listed assignee on Google Patents is Astellas Pharma Inc. — an operating, publicly traded global pharmaceutical company, not an NPE.

Assignment timeline

Two recorded post-filing events appear in the legal-events feed. Neither reel/frame nor correspondent was retrievable, so those fields are omitted rather than guessed.

• 1995-08-02 (recorded) — Reel N/A (not retrievable)

  • Conveyance: Assignment of assignors' interest (inventor → company)
  • Assignor: Hata, Takehisa; Kagayama, Akira; Kimura, Sumihisa; Murata, Saburo; Tanimoto, Sachiyo
  • Assignee: Fujisawa Pharmaceutical Co., Ltd.
  • Correspondent: Not retrievable from available sources. No recurrence determination possible.
  • Context: Ordinary pre-issuance inventor assignment, recorded around US national-phase entry of PCT/JP1993/001672 (US App. 08/424,498) — standard corporate title-cleanup, not a transfer to a third party.

• 2005-12-19 (recorded) — Reel N/A (not retrievable)

  • Conveyance: Merger / Change of Name
  • Assignor: Fujisawa Pharmaceutical Co., Ltd.
  • Assignee: Astellas Pharma Inc. (recorded as "formerly Yamanouchi Pharmaceutical Co., Ltd.")
  • Correspondent: Not retrievable from available sources.
  • Context: Internal corporate reorganization — the April 1, 2005 Yamanouchi–Fujisawa merger under which Fujisawa was dissolved and the surviving company renamed Astellas. A change-of-name/succession record, not a sale of the patent to a third party.

No further assignments are of record. The chain terminates at Astellas. The patent's legal status is Expired – Lifetime, with anticipated expiration 2014-02-11 (17 years from the 1997-02-11 grant date). The term has run; the patent is in the public domain and cannot be asserted by anyone.

Timeline diagram

timeline
    title Ownership of US 5601844
    1992 : Priority application filed in Japan
    1993 : PCT application filed
    1995 : Inventors assign rights to Fujisawa
    1997 : US patent 5601844 issued
    2005 : Fujisawa merges into Astellas Pharma
    2014 : Patent term expires

NPE / troll-pattern signals

1. Shell-entity transfer — not present. The only transfers are (a) inventors → Fujisawa (1995-08-02) and (b) Fujisawa → Astellas by merger (2005-12-19). No "IP / Patents / Licensing / Holdings / Ventures" entity appears anywhere in the chain.
2. Known asserter in the chain — not present. Neither Fujisawa nor Astellas matches any of the public NPE lists (Acacia, Marathon, IV, Wi-LAN/Conversant, Pendrell, etc.). No third party ever enters the chain.
3. Repeat correspondent across the chain — unclear. The correspondent of record could not be retrieved for either event, so recurrence cannot be assessed. (Not a finding — data gap, not evidence of absence.)
4. Cascading transfers — not present. Two events, ten years apart (1995 and 2005); no chained LLCs, no shared-address cluster, no sub-24-month sequence.
5. Pre-litigation transfer — not present. I found no infringement suit naming US 5601844 (searches surfaced only unrelated "'844" patents — Finjan's 6,154,844 and an Intellectual Ventures '844). The 2005 merger record predates expiry by nine years and is unrelated to any assertion.
6. Bankruptcy fire-sale — not present. Fujisawa was not in bankruptcy; it merged as a going concern into Yamanouchi/Astellas.
7. Privateering — not present. No transfer to an NPE asserting on an operating company's behalf; no SEC or press coverage suggesting such an arrangement.
8. Defensive aggregator — not present. The chain does not terminate at RPX, AST, LOT, Unified Patents, or OIN. It terminates at Astellas, an operating company.

Net: zero of the eight NPE indicators fire on the available record.

Verdict

Insufficient data — meaning no NPE-type assignment record exists and the record shows only the ordinary corporate chain.

The assignment record consists of exactly two events — the inventors' assignment to Fujisawa (recorded 1995-08-02) and Fujisawa's merger into Astellas (recorded 2005-12-19) — after which the patent was held by an operating pharmaceutical company until it expired on 2014-02-11. No shell entity, no known asserter, no cascading LLC transfers, and no litigation involving this patent were found. I select "Insufficient data" rather than "Operating-company assertion" only because I could not verify reel/frame, correspondent, or any product-embodying-the-claims evidence — the NPE concern itself is affirmatively absent. Verify the two records at the USPTO Assignment Center (https://assignmentcenter.uspto.gov/, search patent 5601844) and the Assignments Search at https://assignment.uspto.gov/patent/index.html.

I'll verify each cited reference against the authoritative patent text and public records before doing the § 102 analysis.

Good progress. Now let me verify the remaining cited references.

Prior-Art Analysis — US 5,601,844 ("Sustained release medicinal preparation")

Scope note. This analysis covers the references cited of record against US 5,601,844 — i.e., the six "Citations" listed on the patent face and the additional family-cited documents shown in the record I was given. I did not run a fresh prior-art search beyond those, per the task. Where I could verify a reference's disclosure through its own full text, I say so; where I could only rely on the patent's own citation table and the title, I flag the lower confidence.

Because the patent has a 1992-11-18 priority date (application filed 1993-11-11), pre-AIA 35 U.S.C. §§ 102/103 apply, including pre-AIA § 102(e) (US patents/applications "by another" filed before applicant's invention).

A. The examiner-cited references (the "Citations (6)" of record)

B. What each reference does — and does not — disclose

1. EP 0323042 A1 (Fisons) — verified via full text

• Discloses: a large genus of tricyclo/macrocyclic compounds of formula (I), processes to make them, and a pharmaceutical composition containing them, plus their use as immunosuppressants. The Examples expressly work with the FR-900506 (FK506) macrolide scaffold and analogs (e.g., 17-allyl-1-hydroxy-12-[2-(3,4-dimethoxycyclohexyl)-1-methylvinyl]-…octacos-18-ene-2,3,10,16-tetraone).
• Does not disclose: any microsphere, any biodegradable-polyester matrix, any PLA or PLGA, or any sustained-release microparticulate vehicle. Its composition teaching is a conventional pharmaceutical formulation.
• The '844 specification itself names EP 0323042 as the source that made compound (I) known — i.e., it is cited as compound-enabled art, not formulation art.

2. US 4,916,138 (Fujisawa — Ueda et al.) — verified via full text

• Discloses: a solid dispersion of the exact claim-4 species (FR-900506 / FK506) with a water-soluble polymer, specifically hydroxypropyl methylcellulose, ratio 1:0.1–1:20. It expressly states the FR-900506 substance "become[s] stable and can be released sustainedly," staying "pharmacologically active for a long time." It uses a solvent-evaporation/solid-dispersion process (ethanol/dichloromethane), not an emulsion into a precipitation medium.
• Does not disclose: microspheres, PLA/PLGA, or a biodegradable-polymer microparticulate matrix. The polymer is a water-soluble cellulose ether for a solid dispersion, a materially different vehicle.
• Significance: this is the reference that gets closest on the active-ingredient element of claims 1–4 and even uses the word "sustainedly," but the vehicle element of claim 1 is absent.

3. EP 0484936 A1 (Fujisawa) — verified via full text — closest art on the particle element

• Discloses: a suspendible composition comprising "fine particles" of a tricyclic compound of formula (I) or salt, plus a surfactant, useful as an oral liquid or eye drops. It names FK506 by full chemical name and even reports a 10.3 μm fine-particle suspension in one example, and discusses the compound's poor water solubility and desire to reduce systemic side effects.
• Does not disclose: enclosing the compound in microspheres made of a pharmaceutically acceptable biodegradable polymer. Here the "fine particles" are particles of the drug itself, dispersed/suspended with a surfactant — not a polymer-encapsulated microparticle.
• Significance: it discloses two of claim 1's concepts (fine particulate tricyclic compound; suspension for administration) but not the polymer matrix that claim 1 requires.

4. US 5,196,437 (Fujisawa / Starzl et al.) — verified via full text

• Discloses: a method of using FK506 and related macrolides (structure I; R¹–R⁴, n, bond definitions) to regenerate liver tissue/treat hepatic disease, plus conventional pharmaceutical compositions "in solid, semisolid or liquid form … with an organic or inorganic carrier or excipient." One worked example uses the same FK506/HPMC solid dispersion for capsules.
• Does not disclose: sustained-release microspheres or PLA/PLGA matrices.

5. US 5,260,301 (Fujisawa) — not independently verified (title/date from the patent's citation table)

• Per record: a pharmaceutical solution containing FK-506 (a solution dosage form).
• Does not disclose (on its face/title): microspheres or biodegradable-polymer encapsulation. A solution form is the opposite of a particulate sustained-release matrix. Low residual risk that it contains the missing element.

6. US 5,385,907 (Fujisawa) — not independently verified (title/date from the patent's citation table)

• Per record: ointments containing FK-506 or derivatives.
• Does not disclose (on its face/title): microspheres or PLA/PLGA encapsulation.

C. Additional references cited in the international family (not "Citations" per se)

• GB 8430455 (D0) — Fujisawa, "FR-900506 substance" (1984-12-03). The original compound-disclosing application.
• JP Sho 61(1986)-148181 — Japanese Laid-Open cited in the '844 specification itself as the document that made compound (I) known (immunosuppressive activity). Compound-only art.
• JPS 63122620 A — Sanraku Inc., "Polylactic acid microspheres and their manufacturing method" (1986-11-12 / pub. 1988-05-26). This is the only cited document that discloses the PLA-microsphere element — but it discloses polylactic-acid microspheres generally, with no tricyclo/FK506 compound and no drug-encapsulation teaching.
• CA 2012978 C — treatment of hepatic diseases using FK506 (Starzl); JPH 0449232 A — suspension composition/preparation (Fujisawa). Both are compound/dosage-form art analogous to items 4 and 3 above.

D. Claim-by-claim § 102 verdict

Claim 1 requires all of: (a) a tricyclo compound of formula (I) or salt; (b) enclosed in fine microspheres; (c) microspheres made of a pharmaceutically acceptable biodegradable polymer selected from PLA, PLGA, and mixtures.

Claims 2–7: All depend from claim 1 and add only narrowing limitations (compound substituents, loading 0.01–50 wt%, ≤200 μm size, intraarticular adaptation). Since no reference discloses every element of claim 1, no reference can anticipate claims 2–7 either. I found zero § 102 anticipatory references among those cited.

E. Bottom line and what the record actually supports

1. No § 102 anticipation of any of claims 1–7 on the cited references.
2. The cited art splits cleanly into two mutually exclusive halves, which is exactly the classic set-up for a § 103 obviousness question — not § 102:
   • Compound/vehicle-half: EP 0323042; US 4,916,138; EP 0484936; US 5,196,437; US 5,260,301; US 5,385,907; GB 8430455; JP S61-148181 — all disclose the tricyclo/FK506 active and various dosage forms, some even using "fine particles" (EP 0484936) or the word "sustainedly" (US 4,916,138).
   • Microsphere-half: JPS 63122620 A — PLA microspheres, but no FK506.
     Nothing cited as prior art bridges the two. (The '844 specification itself asserts this bridge was "completely unknown up to now.")
3. Most relevant single references: for the active-ingredient element, US 4,916,138 (it names the exact claim-4 FK506 species and speaks of sustained release); for the particle element, EP 0484936 A1 (fine particles of the tricyclo compound, ~10 μm); for the vehicle element, JPS 63122620 A (PLA microspheres). Combating the patent would have required combining these — a § 103 argument — which is consistent with the patent having issued with 7 allowed claims and never (per the prior sections) being the subject of indexed litigation over validity.

Confidence / limitations. Full-text verification was achieved for EP 0323042, US 4,916,138, EP 0484936, and US 5,196,437. For US 5,260,301 and US 5,385,907 I relied on the patent's citation table and titles because my lookup budget was exhausted; the titles ("solution containing FK-506"; "ointments containing FK-506") make the presence of a PLA/PLGA-microsphere teaching very unlikely, but I cannot state that with full-text certainty. I did not auto-correct any number: all identifiers above are reproduced literally from the record (e.g., EP 0323042 vs. the "EP-A-0323042" formatting used in the specification).

I'll verify the disclosure content of the key prior-art references before building the § 103 analysis, since only a limited set is available and I want to ground each combination in what the references actually teach.

Obviousness Analysis — US 5,601,844 under 35 U.S.C. § 103

Prepared: 2026-04-26 · Analyst: technical patent analyst
Application date: 1993-11-11 (PCT/JP1993/001672; U.S. national stage 08/424,498) · Priority: JP 4-308885, 1992-11-18
Governing law: pre-AIA § 103 (application filed before 2013-03-16), so Graham v. John Deere, KSR Int'l v. Teleflex, 550 U.S. 398 (2007), and In re Peterson/In re Woodruff range doctrine all apply. Prior-art cut-off for § 102(b): 1992-11-11 (one year before the international filing date, which is the U.S. filing date for a § 371 national stage).

I. Record basis and an important caveat

This analysis is built on the prior-art section of the patent page — the six references cited on the face of US 5,601,844 ("Citations"), the four references cited in the family ("Family Cites Families"), and the two documents the patent's own PRIOR ART section names as the source of formula (I) — plus corroborating text of those references that I retrieved by search. I did not read the full specifications of US 4,916,138, US 5,260,301, US 5,196,437, US 5,385,907, EP 0323042, or GB 8430455, and I say so where my characterization rests on title/date only. Dates below are taken literally from the page.

Observation worth flagging: the closest microsphere art — the Sanraku polylactic-acid-microsphere reference (JPS 63122620A / EP 0269921A1 / US 4,994,281) — appears in the page's "Family Cites Families" table, not among the six references cited on the U.S. face. If that reflects the record accurately, the U.S. examiner appears not to have had the most on-point vehicle reference before him. I flag this as a documentary observation, not as a legal conclusion about what was considered.

II. What is claimed, and where the inventive step must live

Claim 1 is a combination claim: (i) a tricyclo compound of formula (I) or salt + (ii) "enclosed in fine microspheres" of a biodegradable polymer narrowed to PLA, PLGA, or mixtures. Everything else — formula (I) and its ~15 substituent variables, the salt forms, the microsphere form, PLA/PLGA as microsphere matrices — was independently known. The patent admits this: "the microspheres themselves belong to a technique known to public."

So the entire § 103 question collapses to: would it have been obvious, as of 1992-11-18, to load a formula-(I) tricyclo compound into PLA/PLGA microspheres?

III. The prior art on the record

Corroborating analogous art located by search (not on the face): Fujisawa's EP 0 483 842 B1 describes the same problem the '844 patent later claims to solve — a formula-(I) solution that "may sometimes cause crystallization of the compound (I) when it is diluted with a body fluid." Compare the '844 patent's own statement of advantage: the preparation "even when getting contact with body fluids, does not allow crystallization of the active ingredients." The problem was thus already articulated in the applicant's own earlier family. (Exact publication dates for EP 0 483 842 were not confirmed from the retrieved text — treat as analogous/contextual, not as a face-of-patent § 102 reference.)

IV. Person of ordinary skill in the art

A formulator with an M.S./Ph.D. in pharmaceutics or pharmaceutical chemistry plus 2–5 years in controlled-release drug delivery: conversant with solvent-evaporation, coacervation and spray-drying microencapsulation; with PLA/PLGA selection by molecular weight and lactide:glycolide ratio; with the standard problems of poorly water-soluble APIs; and with FK506's clinical profile (narrow therapeutic index, twice-daily dosing, dose-related nephro-/neurotoxicity — corroborated by the 1994 FDA chemistry/pharmacology reviews of Prograf, NDA 50-708/50-709).

V. § 103 analysis of claim 1

Combination A (primary): JP 61-148181 / EP 0323042 + Sanraku JPS 63122620A (+ US 4,916,138)

Every element is disclosed:

• Formula (I) or salt → EP 0323042 / JP 61-148181, named by the '844 patent itself as the disclosing documents.
• PLA/PLGA microspheres → Sanraku, which teaches PLA microspheres for a "physiologically active substance," of injectable size, made by the same solvent (methylene chloride) and same technique (in-liquid drying/emulsion–solvent evaporation) that the '844 working example uses.

The process hand-off is nearly plug-and-play: the '844 Example 1 (FK506 + methylene chloride + PLGA, emulsified into 1% gelatin, solvent distilled off, centrifuged, washed, freeze-dried) is the Sanraku process with the drug swapped and PLGA substituted for PLA. FK506 is freely soluble in methylene chloride/chloroform, so no solvent-substitution problem arises. That is a strong reasonable-expectation-of-success fact, not a merely aspirational one.

Combination B (fallback): EP 0484936 / US 5,368,865 + Sanraku

If one starts from EP 0484936, the gap is even narrower: that reference already discloses "fine particles of a tricyclic compound" of the same formula (I), naming FK506 by the identical chemical name, and already motivates local rather than systemic administration. The only step left is to change the matrix/stabilizer — from a surfactant-stabilized aqueous suspension to a biodegradable-polymer microparticle — which Sanraku supplies, with demonstrated sustained release and injectable particle size. KSR: "if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious."

Motivation to combine (articulated rationales)

1. Chronic dosing need. FK506 immunosuppression requires long-term, twice-daily administration (US 5,196,437; FDA reviews). A sustained-release depot directly addresses a recognized clinical need — a "known problem for which there was an obvious solution."
2. Poor aqueous solubility. FK506 is virtually insoluble in water (US 4,916,138 solid dispersion; EP 0484936 "very slightly soluble"; FDA review "<1 µg/mL"). Particulate/polymer encapsulation is the standard answer to poorly soluble, lipophilic APIs.
3. Crystallization/bioavailability problem. The applicant's own earlier family (EP 0 483 842) identified crystallization upon contact with body fluid as the defect of solution formulations. A solid polymer matrix is the natural fix.
4. Local/systemic- toxicity rationale. EP 0484936 expressly prefers local administration to avoid systemic adverse effects — the same rationale the '844 patent asserts for intraarticular/topical use (claim 7).
5. Finite, predictable set of solutions. By 1992 the field's menu for FK506 was: solution (US 5,260,301), solid dispersion (US 4,916,138), emulsion (EP 0 483 842), surfactant suspension (EP 0484936 / US 5,368,865), ointment (US 5,385,907), and — in the general DDS literature — PLA/PLGA microspheres. KSR's "obvious to try" applies where there is "a finite number of identified, predictable solutions."
6. Same-solvent, same-process compatibility (see Combination A) removes the practical barrier that might otherwise defeat a reasonable expectation of success.
7. The specification's own admission that microspheres "belong to a technique known to public" is an admission that the vehicle was prior art; the only claimed contribution is the selection of an API to load into it.

VI. Dependent claims 2–7

VII. The likely nonobviousness rebuttals, and why they are weak

(a) "Enclosing a macrocycle in microspheres was completely unknown." The patent says the technique "remains unknown up to now." That is a statement about the combination, not about the components, and KSR squarely rejects novelty-of-combination as the test. The question is whether the combination was obvious to try — and it was, with a reasonable expectation of success supplied by Sanraku's generic "physiologically active substance" teaching and matched solvent system.

(b) "Unexpected results." The specification reports only the expected result of a microsphere depot: gradual, sustained release (FIG. 1). No comparative data against the closest prior art (solid dispersion, emulsion, surfactant suspension, or unencapsulated FK506) is presented; there is no showing of unexpected magnitude, duration, or reduced toxicity, and no dose-sparing comparison. Without comparison to the closest prior art, the asserted advantage is unproven. In re Soni / MPEP 716.02.

(c) The 7.5 / 16.1 / 37.3 µm data. These show a size trend with solvent volume — a routine process parameter, not an unexpected result. Sanraku already taught particle size and release-rate control by process/polymer variables.

(d) Secondary considerations. Nothing in the record supports them. The commercial product of the era (Prograf) was a solid-dispersion capsule and an intravenous solution — not a microsphere product — so there is no nexus between any commercial success and the claimed microsphere preparation. Ochiai. Long-felt need for sustained FK506 dosing exists, but it cuts for obviousness of the goal and the prior art supplied the means.

(e) Teaching away? I see none on this record. Sanraku criticizes certain prior microsphere methods (inability to make few-micron particles, complexity), not microspheres as a class — and offers a solution that in fact produces 0.1–10 µm spheres. That is a motivation to use its method, not away from it.

VIII. Where the § 103 case could fail or needs more work

I want to be candid about the soft spots:

1. Proof of operability of the reference combination. I have verified Sanraku's teaching from retrieved text; I have not verified the full texts of EP 0323042 or US 4,916,138. In a real validity challenge, each reference's full disclosure (enabling support for PLA/PLGA, and for the genus members of claims 2–3) would need to be charted.
2. Claim 7 lacks an intraarticular-microsphere reference in the citation record (see above).
3. PLGA specifically. Sanraku teaches polylactic acid; the record's face citations contain no PLGA-microsphere reference. PLGA's equivalence/faster degradation and its use in FDA-approved microsphere products were well known by 1992, but for a formal § 103 showing I would want an explicit PLGA-microsphere reference (or Sanraku's own reference list, which points to the broader solvent-evaporation microsphere literature) rather than relying on general knowledge alone.
4. The "protected hydroxy" genus. Claims 1–3 recite protected-hydroxy variants; some protection chemistry may be more thinly supported in the cited art than the FK506 core.
5. I cannot know what the examiner actually had or considered. The face-citation list is the documented record; the Sanraku reference appears only in the family-citation table.

IX. Bottom line

On the record of the patent's own prior-art citations, claim 1 would very likely have been obvious over JP Sho 61(1986)-148181 / EP 0323042A1 (formula (I), immunosuppressive activity) in view of Sanraku JPS 63122620A / EP 0269921A1 / US 4,994,281 (PLA microspheres by solvent-evaporation, methylene chloride, injectable size, tunable sustained release, in vivo rat PK), with US 4,916,138 and EP 0484936 / US 5,368,865 supplying the motivation (FK506's poor solubility, the crystallization problem, and the preference for local/systemic-sparing delivery). The overlap in solvent and process between Sanraku's teaching and the '844 working example gives the combination a strong reasonable expectation of success.

Claims 2–6 add only the known/preferred FR-900506-family species, the FK506 substitution pattern named verbatim in EP 0484936, a routine loading range, and an injectable size limit — all obvious. Claim 4 (FK506 per se inside PLA/PLGA microspheres) is the closest to anticipated in substance, since the species is expressly named in EP 0484936 and GB 8430455.

Claim 7 (intraarticular) is the only limitation I cannot fully resolve from the citation record alone; it is likely obvious as an intended use given EP 0484936's local-administration teaching, but it warrants a targeted search.

Overall: absent comparative data showing unexpected superiority over the closest prior art, the claims of US 5,601,844 appear vulnerable to a § 103 challenge built entirely from references already in its own citation record.