US 6387918

I'll search for this specific patent number and any associated litigation.

US Patent 6,387,918 — Analyst Summary

Note on methodology / scope: I searched for the number "6387918" and related terms. I do not have direct API access to USPTO PatentCenter or the CAFC docket system; my findings come from indexed public web sources (Google Patents, Justia, patent family records, and litigation filings surfaced by search). Where I could not confirm something authoritatively, I say so below.

1. Bibliographic data (from the authoritative patent text provided)

Foreign family members (for context, from the record): EP0977565B1, JP3396888B2, KR100490357B1, CN1178656C, CA2282345C, AU727337B2, HU226163B1, IL131298A, AR011846A1, TW450810B, EA003580B1, BR9807234B1, NO325103B1, and others.

2. Abstract (verbatim)

"A pharmaceutical composition comprising a tricyclic compound (I) or its pharmaceutically acceptable salt, an oil substance, a surfactant, a hydrophilic substance, water, and optionally a pH control agent, with enhanced stability, absorbability and/or a low irritation potential, is provided."

3. Plain-language overview of the independent claims

The patent has two independent claims: claim 1 (composition) and claim 9 (process). Claim 10 depends on claim 9; claims 2–8 depend directly or indirectly on claim 1.

Claim 1 — the composition (independent)

A topical pharmaceutical composition with six enumerated parts:

• (A) Active ingredient: a "tricyclic compound of Formula (I)" (the macrolide immunosuppressant family that includes FK506/tacrolimus and its analogs) or a pharmaceutically acceptable salt thereof. Formula (I)'s variable definitions (R¹–R²³, X, Y, n, etc.) are recited essentially in full in the claim.
• (B) Oil substance: specifically a combination of isopropyl myristate and diethyl sebacate — i.e., one monohydric-alcohol fatty acid ester plus one dibasic-acid diester, which the specification notes gives the best stability/absorbability/irritation balance.
• (C) Surfactant: limited to one of four named classes — a polyoxyethylene alkyl ether, a polyoxyethylene sorbitan fatty acid ester, a pentaglycerol fatty acid ester, or a glycerol fatty acid ester.
• (D) Hydrophilic substance: any pharmaceutically acceptable substance "capable of imparting viscosity to liquids" (a thickener/gelling agent).
• (E) Water.
• (F) Optionally a pH control agent.

In substance: a topically applied, water-containing semi-solid (cream-type) vehicle in which the drug is dissolved in a defined oil blend, emulsified with a defined surfactant class, and thickened with a hydrophilic polymer.

Claim 9 — the process (independent)

A process for making the claim-1 composition, comprising:

1. mixing a solution that contains the tricyclic compound (or its salt), the oil substance, and the surfactant with water to prepare an emulsion; and
2. mixing that emulsion with the hydrophilic substance (and optionally the pH control agent).

The specification describes a preferred order of operations: dissolve drug + oil + surfactant at elevated temperature (~50–90 °C, preferably 60–80 °C), add pre-heated water and homogenize, cool (e.g., to ~30 °C), then combine with the pre-formed hydrophilic gel and adjust pH.

Notable dependent claims (context, not independent)

• Claim 2: amounts — surfactant 0.1–15 wt%, oil 2–50 wt%, hydrophilic substance 0.1–10 wt%.
• Claim 3: composition pH 3.5–6.
• Claim 4: hydrophilic substance is a carboxyvinyl polymer (e.g., Carbopol).
• Claim 5: surfactant is a polyoxyethylene sorbitan fatty acid ester.
• Claim 6: narrows the Formula (I) substituents.
• Claim 7: the compound is specifically FK506 Substance (tacrolimus) — the 17-allyl-…-octacos-18-ene-2,3,10,16-tetraone named in full.
• Claim 8: pH about 4–5.
• Claim 10: variant process where the hydrophilic substance (and optional pH agent) is first mixed with water, and that premix is then combined with the emulsion.

4. Litigation / CAFC 2026 dockets

I did not find any authoritative evidence of a Court of Appeals for the Federal Circuit (or district court) case in 2026 involving US 6,387,918 specifically. I want to flag this clearly rather than overstate:

• The patent expired (anticipated expiration 2018-02-18), so it is unlikely to be an asserted patent in current infringement litigation.
• Searches surfaced Astellas/Protopic-related litigation over tacrolimus, but the asserted patents in those actions were different numbers — e.g., the 2010 Astellas v. Nycomed (D.N.J.) case asserted US 5,665,727 and US 5,385,907, not the '918 patent.
• Caution — do not conflate similar numbers: Documents referencing a "'918 patent" in the Glenmark/Veloxis tacrolimus dispute appear to refer to a different patent (a Veloxis stabilized-tacrolimus composition), not US 6,387,918. Likewise, JP 6387918 B2 is an unrelated Japanese patent (Konica Minolta, image forming apparatus), and US 9,647,918 is an unrelated wireless-device patent. None of these is US 6,387,918.

If a 2026 CAFC docket on this exact patent exists, I could not confirm it with the tools available; treat the litigation section as unverified.

5. Technical/legal significance (short)

This patent is the composition-of-matter/vehicle patent behind Astellas's topical tacrolimus cream line (commercially the Protopic franchise). Its claim 1 is notably narrowed to a specific oil blend (isopropyl myristate + diethyl sebacate) and four surfactant classes — a scope consistent with the inventors' stated finding that this particular combination delivered superior stability, transdermal absorbability, and reduced skin irritation relative to prior ointment/lotion art (e.g., the ointment of JP H5-17481 and the lotion of WO94/28894 cited in the background). The transdermal data in the patent (Table 1) reports AUC[0–24 hr] > 30 ng·hr/mL in rats for several formulations.

Confidence statement: The bibliographic data, abstract, and claim text above are drawn from the full authoritative patent text supplied and are high-confidence. The litigation/CAFC portion is not authoritative — I found no 2026 CAFC docket naming US 6,387,918, and I explicitly could not verify one.

I'll search for litigation involving US Patent 6387918.

Let me search additional litigation-specific databases.

Let me check the litigation databases directly.

Summary of Findings: Litigation Involving U.S. Patent No. 6,387,918

No litigation (district court infringement suits, CAFC appeals, PTAB proceedings, or ITC actions) involving U.S. Patent No. 6,387,918 was found. Based on searches of litigation-oriented sources (Unified Patents litigation portal, CourtListener/RECAP, Justia, Docket Alarm, paragraphfour.com, and the Federal Circuit blog), no complaint, docket, or proceeding in which U.S. 6,387,918 was asserted as a patent-in-suit has surfaced.

Critical identification caution (do not auto-correct)

Before reporting "no litigation," it is important to distinguish U.S. 6,387,918 from near-identical numbers that DO appear in tacrolimus litigation:

• U.S. Patent No. 6,387,918 — "Pharmaceutical composition," assignee Astellas Pharma Inc. (originally Fujisawa Pharmaceutical Co., Ltd.), issued May 14, 2002, priority Feb. 20, 1997. This is the topical/hydrophilic semi-solid tacrolimus (FK506) cream formulation patent. Verified via Google Patents and Justia.
• U.S. Patent No. 9,545,918 — "Stabilized Tacrolimus Composition." This is the "'918 patent" repeatedly referenced in the Veloxis v. Alkem / Veloxis v. Sun ANDA litigation (e.g., D. Del. Nos. 1:24-cv-00784, 1:24-cv-00726). These are different patents. The Veloxis cases concern oral extended‑release tacrolimus (ENVARSUS XR®), not the topical formulation of 6,387,918.
• JP Patent No. 6387918 ("JP6387918B2") — a Konica Minolta image-forming-device patent. Completely unrelated (a Japanese, non-U.S. patent).
• Other tactile numeric coincidences (e.g., a North Macedonian company registration number "6387918") are likewise unrelated.

Related (but distinct) tacrolimus litigation — NOT involving 6,387,918

For context, the closest tacrolimus litigation is not about U.S. 6,387,918:

Note that none of these assert U.S. 6,387,918.

Caveats and limitations

• I was unable to access PACER, the Unified Patents litigation caselist, or Docket Alarm directly in this session (search returns were indirect). This conclusion rests on keyword searches of indexed litigation/complaint PDFs and public patent databases, not a full docket-by-docket query.
• U.S. 6,387,918 is recorded as Expired – Lifetime (anticipated expiration Feb. 18, 2018), per Google Patents. Its expiration predates most recent tacrolimus generic activity, consistent with it never having been the subject of reported infringement litigation.
• If you require a definitive negative, a direct PACER search of all U.S. district courts and a CAFC docket query for "6,387,918" is recommended, as I could not execute those directly here.

Bottom line: On the available evidence, no known litigation involves U.S. Patent No. 6,387,918. Any references to a tacrolimus "'918 patent" in litigation are to U.S. Patent No. 9,545,918, a different patent.

I'll verify the structured "no proceedings" default against live sources before writing the report.

Let me run additional targeted searches to confirm the negative and check for related proceedings.

Let me check the European counterpart proceedings and confirm no reexamination/appeal activity, as context.

I ran multiple targeted searches (IPR/PGR/CBM keyword searches, number-string searches across PTAB and litigation document indices, and cross-checks against the near-miss patent numbers identified in the litigation section) and could not surface any AIA trial proceeding involving U.S. 6,387,918. The structured "PTAB proceedings on file" block likewise returns zero. The report below reflects that verified negative and explains why it is a meaningful one.

Proceedings overview

Total AIA trial proceedings on U.S. Patent No. 6,387,918: 0. Breakdown: 0 active, 0 with claims invalidated, 0 with claims sustained, 0 settled, 0 institution denials. The patent has never been challenged at the PTAB, which — given the statutory window and the commercial profile of the patent — means there is no IPR-based invalidity record to lean on: a defendant cannot point to a canceled claim, cannot invoke estoppel against the patent owner, and must build any invalidity case from scratch in district court, where the full universe of prior art remains available (and unconstrained by § 315(b) time bars, IPR claim-construction practice, or the Board's amendment-friendly procedures).

No proceedings to itemize

The canonical source for this section — the USPTO Open Data Portal "PTAB proceedings on file" structured block supplied with this task — returns no AIA trial proceedings for U.S. 6,387,918 as of the most recent ingest. No IPR, PGR, or CBM trial number exists to report, and per your instruction I will not invent one. Consequently there is no:

• presiding judge panel,
• petition ground set (§ 102 / § 103 / § 112),
• institution decision (instituted / denied / partially instituted),
• Final Written Decision at claim-level granularity,
• settlement or termination record,
• or Federal Circuit appeal (no FWD, therefore no appealable Board decision and no CAFC docket).

All ten claims of the patent — claims 1–10, including independent claim 1 (the hydrophilic semi-solid tacrolimus composition requiring the isopropyl myristate/diethyl sebacate oil combination) and independent claim 9 (the process) — are therefore UNTESTED at the PTAB.

Why this negative is real, not a data gap

Three structural checks support the "genuinely no proceedings" conclusion rather than "the database is thin":

1. The statutory vehicle existed and had a live window. IPR became available 2012-09-16 (AIA § 6). U.S. 6,387,918 was in force from its 2002-05-14 issuance until its anticipated expiration on 2018-02-18 — a ~5.5-year IPR window, coinciding almost exactly with the period when generic tacrolimus topical (Protopic®) activity and the first tacrolimus ANDA disputes were underway. A patent of this scope, in a molecule this heavily litigated, would ordinarily have attracted at least one IPR petition in that window. None appears.
2. PGR and CBM were categorically unavailable, which is not the explanation for the absence of AIA activity but does mean IPR was the sole available AIA route:
   • PGR requires an effective filing date on or after 2013-03-16. U.S. 6,387,918 has a priority date of 1997-02-20 and a § 371(c)(1)/(2)/(4) date of 1998-02-18 (PCT/JP1998/000665). It is far outside PGR eligibility.
   • CBM requires a "covered business method" patent — a financial-product or financial-service patent, subject to the "technological invention" exception. A topical immunosuppressant cream formulation does not qualify.
   • So there was never a CBM or PGR petition to find; IPR was the only test available, and nobody filed one.
3. The litigation section already isolated the number-confusion problem. As noted there, the tacrolimus "'918 patent" that actually appears in Veloxis v. Alkem (D. Del. 1:24-cv-00784) and Veloxis v. Sun (D. Del. 1:24-cv-00726) is U.S. 9,545,918 ("Stabilized Tacrolimus Composition," oral extended-release), not U.S. 6,387,918. See the Alkem counterclaims PDF at paragraphfour.com, which describes the '918 patent's claim 1 as requiring "tartaric acid" and "polyethylene glycol and poloxamer" — that is the oral solid-dispersion patent (application serial no. 13/029,304), definitively not the topical cream patent at issue here. Likewise, JP6387918B2 is a Konica Minolta image-forming-device patent (JPO publication), unrelated.

Near-miss proceedings I checked and excluded

Strategic summary

Claim status. All ten claims of U.S. 6,387,918 are UNTESTED — there is no canceled claim, no confirmed claim, and no claim that has been the subject of an institution decision. Unlike a patent that has been through two IPRs and emerged with a narrowed but hardened claim set, this patent's claims carry no PTAB pedigree at all. Claim 1 (composition: tricyclic compound + isopropyl myristate/diethyl sebacate oil combination + specified surfactant classes + hydrophilic substance + water + optional pH control agent), dependent claims 2–8, and independent process claim 9 (with claim 10) stand exactly as issued on 2002-05-14 — including the 2003-06-17 certificate of correction noted in the legal events.

Estoppel landscape. Because no petitioner ever filed an IPR, § 315(e)(2) estoppel is a null set. No party, and no privy of any party, is barred from raising any ground. For a defendant evaluating invalidity today, the practical consequence is inverted from the usual IPR-follows-litigation posture:

• Every § 102 and § 103 combination that any challenger would have put in a petition remains fully available in district court or, if a live controversy still existed, in a fresh IPR.
• There is no adverse claim construction from the Board to work around, and no patent-owner-driven narrowing amendment under § 316(d) (motion to amend) that a challenger would have to carry through a § 315(e)(2)-style estoppel analysis.
• Conversely, a defendant gets no help: no FWD findings of unpatentability, no expert testimony on the record, no Exhibit list of prior-art references tested against the claims. Any obviousness theory must be developed from scratch.

Pattern signals. There is no pattern to report: no repeat petitioner (zero petitioners), no patent-owner appeal practice at the PTAB (the patent owner, Fujisawa → Yamanouchi merger → Astellas Pharma Inc., never appeared before the Board on this patent), and no defensive aggregator in the chain — no Unified Patents, RPX, or similar entity petitioned against U.S. 6,387,918. The absence of aggregator activity is consistent with the patent's subject matter (a topical formulation with a limited, dermatology-scoped commercial footprint) rather than with any defensive-licensing campaign against it.

Practical post-expiration posture. Two realities dominate any assessment today (2026-10-01):

1. The patent is recorded as Expired – Lifetime with an anticipated expiration of 2018-02-18, per Google Patents. There is no injunctive relief available and no ongoing royalty exposure for current conduct.
2. Under 35 U.S.C. § 286, damages are recoverable only for infringement occurring within six years before suit — i.e., on or after approximately 2020-10-01. Because the patent expired 2018-02-18, that look-back window is empty. Any assertion of this patent today is, at minimum, a damages-limitations problem and, more likely, a non-starter on standing/remuneration grounds.

The combination — never IPR-challenged, but now expired with a closed damages window — is a different signal from "hardened patent." It means the patent was never stress-tested at the Board during its enforceable life, and any assertion of it now is burdened by § 286 rather than by the PTAB.

CAFC / appeal posture. No Final Written Decision issued, so there is no Board decision that could have been appealed under 35 U.S.C. § 319 / § 141. There is accordingly no Federal Circuit docket number to report for this patent. (For the avoidance of doubt, the "'918" patent in the Novartis v. MSN appeal pending at the Federal Circuit, No. 25-1927, is U.S. 11,096,918 — a different patent, different owner, different technology.)

Recommended next steps

If you are a defendant facing an assertion of U.S. 6,387,918:

1. Do not file an IPR. There is nothing to invalidate defensively that would help you: the patent is expired (anticipated expiration 2018-02-18 per Google Patents), so there is no prospective infringement to enjoin and no royalty base to attack at the Board. An IPR would buy you no injunction relief and cannot revive a defense you do not need.
2. Lead with the § 286 damages bar. If a demand letter or complaint cites U.S. 6,387,918 against activity occurring after 2018-02-18, the patent cannot reach it — the claims are expired, and under 35 U.S.C. § 286 no damages are recoverable for infringement more than six years before filing. Confirm the asserted acts and dates against the expiration date before drafting.
3. Verify the patent number in the demand letter. This is the single most likely error to exploit. The litigation section flags it explicitly: tacrolimus "'918" references in current ANDA litigation (Veloxis v. Alkem, D. Del. 1:24-cv-00784; Veloxis v. Sun, D. Del. 1:24-cv-00726) are to U.S. 9,545,918, an oral extended-release solid-dispersion patent requiring tartaric acid and PEG/poloxamer. If a letter cites "the '918 patent" while describing topical tacrolimus, the numbers have been conflated and the assertion may be misdirected. See dedc24cv0784A.pdf for the counterclaim language distinguishing them.
4. If a good-faith challenge is nonetheless needed (e.g., a declaratory-judgment posture or a licensing dispute over past sales), you retain the entire prior-art universe: no § 315(e)(2) estoppel applies to any ground, because no IPR petition was ever filed. Start from the references actually cited during prosecution and in the patent's own description — including EP 0474126 (Fujisawa, ointments containing tricyclic compound), JPH 06183970 (medicinal composition), US 5,368,865 (suspendible composition), WO 96/13249 (Novartis), and EP 0753297 (Fujisawa lotion) — all listed among the citations on the patent's face.

If you are the patent owner or licensor today:

• There is no Board record to cite in support of validity; do not represent that the claims "survived" or were "confirmed" at the PTAB — they were never examined there. Any such statement would misstate the record.

If you need a definitive negative (verification caveat):

• I could not execute direct queries against PTAB E2E / PTAB Center or PACER in this session; the conclusion rests on the USPTO Open Data Portal structured block plus keyword searches of indexed PTAB filings. For a belt-and-suspenders confirmation, run a patent-number query in USPTO PTAB Center (E2E) and the USPTO PTAB Decisions database, and a "6387918" docket search on CourtListener/RECAP. To date, no proceeding has surfaced from any source I could reach.

Bottom line: U.S. 6,387,918 has no PTAB history of any kind — zero petitions, zero institutions, zero Final Written Decisions, zero appeals. No claim of the patent is canceled or sustained; all ten claims are untested. The absence of any IPR is not the "patent is too strong to attack" signal, but rather the "patent expired before anyone needed to attack it at the Board" signal: it expired on 2018-02-18, and the six-year damages look-back under § 286 now reaches back only to approximately 2020-10-01, a period during which the patent was no longer in force. Any assertion of this patent today should be met first with the § 286 and expiration arguments, and second — if the number has been conflated with U.S. 9,545,918 — with a correction of the record.

I'll research the assignment record for US 6,387,918, starting with the legal events already embedded in the patent text and then verifying via USPTO Assignment Center and related sources.

Let me try to access the USPTO Assignment Center records directly and cross-reference the assignee/inventor details.

Let me look for the assignment record's correspondent (the attorney of record) and cross-check with uspto.report and assignment databases.

Based on the legal events embedded in the authoritative patent text, cross-checked against the Astellas/Yamanouchi/Fujisawa merger record and the prior litigation section, here is the ownership reconstruction for US 6,387,918.

Note on scope of verification: The USPTO Assignment Center (assignmentcenter.uspto.gov) and its legacy mirror (assignment.uspto.gov) were not directly reachable in this session; the assignment entries below are taken from the patent's own recorded legal-events table (Google Patents, sourced from the USPTO assignment database) and corroborated by corporate records. Any field I could not independently confirm — specifically the correspondent of record — is labeled as not retrieved rather than guessed.

Inventors

• The applicant/assignee of record is Fujisawa Pharmaceutical Co., Ltd. (the PCT filing PCT/JP1998/000665 and the resulting US national-stage entry US 09/367,698 were Fujisawa's), and the assignment free-text names the assignors as "YAMANAKA, MASAYUKI; SHIMOJO, FUMIO; UEDA, SATOSHI; AND OTHERS" — consistent with all six inventors being Fujisawa employees at the time of filing.
• Unusual-pattern check — no fire-sale precursor present. There is no evidence of the inventor team departing the original assignee within 12 months. On the contrary, inventor Satoshi Ueda reappears years later as an inventor on Fujisawa/Astellas's follow-on topical tacrolimus filings (e.g., US 2004/0220204, "Pharmaceutical composition comprising a tricyclic compound for the prevention or treatment of skin diseases"). Continued employment of the inventive team is the inverse of the pattern that typically precedes a portfolio divestiture.

Original assignee

• Entity on the issued patent: Fujisawa Pharmaceutical Co., Ltd. (Osaka, Japan).
• Primary line of business: Research-based pharmaceutical manufacturer. Fujisawa commercialized tacrolimus, the active in this patent, as both Prograf (oral/systemic immunosuppressant) and Protopic (topical tacrolimus, FDA NDA 050777, approved 2000-12-08; manufactured at Fujisawa's/now Astellas Pharma Manufacturing plant, Grand Island, NY — see the Buffalo Business First report on the merger).
• Did they ship a product embodying these claims? Uncertain / flag. The claims (claim 1) are directed to a hydrophilic semi-solid oil-in-water emulsion cream containing isopropyl myristate plus diethyl sebacate and a surfactant. Fujisawa's flagship topical, Protopic, is an ointment, not the cream of these claims; the specific oil-in-water cream form later appears in third-party filings (e.g., Marlho/マルホ's tacrolimus cream family — JP 5674786 B2, JP 6084579 B2). So while Fujisawa was unquestionably operating in this space, I cannot confirm that a commercial product literally practiced the issued claims. This is a claim-scope/vs.-product question, not an ownership question.
• Current status of the original assignee: Dissolved by merger. Fujisawa merged into Yamanouchi Pharmaceutical Co., Ltd. (the surviving entity), which was renamed Astellas Pharma Inc. effective 2005-04-01. The successor, Astellas Pharma Inc., is an operating company (no bankruptcy, no dissolution, no acquisition by an NPE).

Assignment timeline

Two assignment events are recorded. Both are house-chain events (original employment assignment + corporate merger/change of name); there is no third-party or NPE transfer.

• 1999-08-02 (executed) / recorded 2001-09-19 — Reel 012174/0407

  • Conveyance: Assignment (Assignment of Assignors' Interest)
  • Assignor: Yamanaka, Masayuki; Shimojo, Fumio; Ueda, Satoshi; and others (the six inventors)
  • Assignee: Fujisawa Pharmaceutical Co., Ltd. (Japan)
  • Correspondent: Not retrieved in this session — the Assignment Center correspondent field could not be pulled; the Google Patents legal-events table does not carry it. No correspondent pattern can therefore be asserted for this link.
  • Context: Initial inventor→employer assignment. Execution date (Aug 1999) aligns with the US national-stage entry of the Feb-1998 PCT, i.e., standard employment/patent-rights assignment, not a sale.

• 2005-04-01 (executed/effective) / recorded 2005-12-19 — Reel 016902/0759

  • Conveyance: Merger / Change of Name
  • Assignor: Fujisawa Pharmaceutical Co., Ltd.
  • Assignee: Astellas Pharma Inc. (recorded as formerly Yamanouchi Pharmaceutical Co., Ltd.)
  • Correspondent: Not retrieved in this session (see above).
  • Context: Internal reorganization only. Fujisawa was dissolved into Yamanouchi, which was renamed Astellas (effective 2005-04-01, per the joint Astellas press materials). Beneficial ownership stayed within the same corporate family; no third party entered the chain. Note the literal reading of the recorded owner name: Astellas is described as "formerly Yamanouchi Pharmaceutical Co., Ltd.," which is legally accurate — Yamanouchi was the surviving entity that renamed itself — even though the assignor on this record is Fujisawa. Do not auto-correct this; it is consistent with the merger structure.

Related non-assignment legal events (for completeness): Certificate of Correction 2003-06-17; maintenance fees paid 2005-10-24 (4-yr), 2009-10-14 (8-yr), 2013-10-16 (12-yr); anticipated expiration 2018-02-18; status Expired – Lifetime. The timely payment of every maintenance fee by the Fujisawa/Astellas line is itself evidence of a continuously maintained operating-company asset.

Timeline diagram

timeline
    title Ownership of US 6387918
    1997 : Inventors file PCT application
    1999 : Inventors assign rights to Fujisawa
    2002 : Patent issued to Fujisawa
    2005 : Fujisawa merges into Astellas
    2018 : Patent expires

NPE / troll-pattern signals

1. Shell-entity transfer — not present. No assignee carries an "IP / Patents / Licensing / Holdings / Ventures" suffix and no single-purpose LLC appears in either recorded link (Reel 012174/0407 = Fujisawa, an operating pharma; Reel 016902/0759 = Astellas, an operating pharma).

2. Known asserter in the chain — not present. Neither assignee appears on any recognized NPE roster (Acacia, Marathon, IV, IPNav, Wi-LAN, Conversant/Mosaid, Vringo, Pendrell, Round Rock, etc.). Both are branded pharmaceutical manufacturers.

3. Repeat correspondent across the chain — unclear. The correspondent of record for both Reels (012174/0407 and 016902/0759) could not be retrieved in this session, so no recurrence can be established. Note this is a weak signal by construction here: with only two links — one employment assignment and one merger/change-of-name — recurrence would be expected of ordinary corporate/outside counsel rather than indicating an NPE recording shop.

4. Cascading transfers — not present. Only two recordings exist across ~6 years (1999→2005), both executions of the same corporate family. No consecutive chained-LLC transfers within 24 months.

5. Pre-litigation transfer — not present. Consistent with the prior litigation section, no infringement suit naming US 6,387,918 was found, so there is no assignment dated within 6 months before a first suit. (The 2005 merger recording predates any hypothetical litigation by years and was not assertion-motivated.)

6. Bankruptcy fire-sale — not present. The 2005 event is a merger, not a Chapter 7/11 sale; Fujisawa was absorbed into Yamanouchi, and Astellas continued as a going concern.

7. Privateering — not present. No transfer out to a third-party NPE asserting on the operating company's behalf; ownership remained in-house.

8. Defensive aggregator (anti-NPE) — not present. The chain does not terminate at RPX, AST, LOT, Unified Patents, or OIN; it terminates at Astellas, an operating manufacturer.

Verdict

Insufficient data (as to any NPE classification — substantively a clean, non-NPE operating-company chain).

Justification: the Assignment Center record for US 6,387,918 consists of only the original inventor→Fujisawa assignment (Reel 012174/0407, executed 1999-08-02) plus a corporate merger/change-of-name recording to Astellas Pharma Inc. (Reel 016902/0759, effective 2005-04-01). There is no third-party transfer in the chain — the patent has remained within the original corporate family (Fujisawa → renamed surviving entity Astellas) since filing — so none of the NPE/assertion categories is supported by evidence, and I decline to infer one from naming. If a rubric requires a positive operating-company label, note the caveat that this specific patent was never asserted (per the prior litigation section) and that I could not confirm a commercial product literally embodying claim 1, so "operating-company assertion" would overstate the record.

Verify at the USPTO Assignment Center (search patent number 6387918): https://assignmentcenter.uspto.gov/ (legacy mirror: https://assignment.uspto.gov/patent/index.html).

Two explicit caveats/contradiction checks:

• Correspondent field gap: I could not retrieve the correspondents of record, the one field the task treats as most probative. If a subsequent pass reaches Assignment Center, pull the correspondent for both Reels to close signal #3.
• No contradiction with the prior litigation section: this ownership picture is fully consistent with that finding of no litigation naming US 6,387,918. Any litigation reference to a tacrolimus "'918 patent" is to U.S. 9,545,918 (Veloxis), a different patent — do not conflate.

I'll search for the specific patent number and its citations.

Let me gather details on each cited reference.

Prior-Art Analysis — U.S. Patent No. 6,387,918 B1

Methodology note. I confirmed the patent as US 6,387,918 B1 ("Pharmaceutical composition," Fujisawa Pharmaceutical Co., Ltd., application US 09/367,698, PCT/JP1998/000665) via the Google Patents record at https://patents.google.com/patent/US6387918/en. I did not return results for near-numbers, and I explicitly distinguish them below. Direct USPTO PatentCenter/PAIR access was not available in this session; the citation lists below are taken from the authoritative patent text supplied and cross-checked against Google Patents / FreePatentsOnline / Espacenet records surfaced by search. Where I could not verify a reference's disclosure (as opposed to its bibliographic face data), I say so.

Critical identifier caution (per the strict no-auto-correct rule):

• US 6,387,918 B1 is the subject patent (topical tricyclic/FK506 cream).
• US 6,545,918 B2 / US 9,545,918 B2 are different patents (Veloxis "Stabilized Tacrolimus Composition" family) that appear in tacrolimus litigation — not this patent.
• JP 6387918 B2 is an unrelated Konica Minolta patent.
  None of these are the subject of this analysis.

A. The citation record on the face of US 6,387,918

The patent's own "Patent Citations (7)" list, its single "Non-Patent Citation (1)," and its one "Family Cites Families (1)" entry are:

Note the patent cites 5 references on its "Citations (5)" tab and 7 in the full "Patent Citations (7)" tab; the two references unique to the larger tab (US 5,385,907 and US 5,939,427) are the U.S. counterparts of EP 0 474 126 and EP 0 753 297, respectively.

B. Reference-by-reference analysis (with §102 assessment)

1 & 2. EP 0 474 126 A1 and its U.S. equivalent US 5,385,907

• Full citation: EP 0 474 126 A1, "Ointments containing tricyclic compound," Fujisawa Pharmaceutical Co., Ltd.; JP priority 2-235177 (1990-09-04); published 1992-03-11. U.S. equivalent: US 5,385,907, "Ointments containing FK-506 or derivatives thereof," inventors Asakura, Murakami, Kanagawa, Nakate; app. US 08/062,330; issued 1995-01-31.
• Disclosure: An ointment comprising (i) tricyclic compound (I) — with FK506 named in full, including the 17-allyl-…-octacos-18-ene-2,3,10,16-tetraone — (ii) a solubilizing and/or absorption-promoting agent, and (iii) an ointment base. Claim 1 of the AU counterpart (AU 656145 B2) recites the promoter as, e.g., a lower alkanediol, lower alkylene carbonate, alkane dicarboxylic ester, higher alkane carboxylic glycerin ester, higher alkane carboxylic alkyl ester, higher unsaturated alcohol, or azacycloalkane, in ~1–30% w/w, with drug at ~0.01–10% w/w.
• §102 assessment: This is the closest prior art for the active ingredient and topical route, and it expressly names FK506/tacrolimus. However, for anticipation of claim 1 it fails: it does not disclose (B) the particular oil combination of isopropyl myristate + diethyl sebacate together, nor (D) a hydrophilic viscosity-imparting substance in (E) water as the continuous cream vehicle (it is an oleaginous ointment base). It therefore does not anticipate claim 1 and does not anticipate dependent claims 2–8 (each incorporates the full claim-1 composition). Its chief role is §103 obviousness art against the vehicle. I found no claim for which this reference is a clean §102 reference. (Confidence: high on bibliographic data and claim-1 elements; high that it is not anticipatory because the specific dual-oil blend is absent.)

3. US 5,368,865 A

• Full citation: US 5,368,865, "Suspendible composition and process for preparing the same," Fujisawa Pharmaceutical Co., Ltd.; priority 1990-11-08; issued 1994-11-29.
• Disclosure: A suspendible (aqueous suspension) composition of fine particles of tricyclic compound (I) plus a pharmaceutically acceptable surfactant; stated utility is as an oral agent or eye drops. It addresses the poor water solubility of FK506 by particulate suspension, not by an oil-dissolved emulsion cream.
• §102 assessment: Discloses elements (A) tricyclic compound, (E) water, and possibly (C) a surfactant class. It does not disclose (B) the isopropyl-myristate/diethyl-sebacate oil blend nor (D) the hydrophilic thickening substance required by claim 1. No anticipation of any composition claim (1–8); relevant only as general background on formulating FK506 with surfactants. (Confidence: high.)

4. JP H06-183970 A (and its CA abstract, XP002070103)

• Full citation: JP H06-183970 A, "Medicinal composition," Fujisawa Pharmaceutical Co., Ltd.; filed 1992-12-16; published 1994-07-05. Abstracted as Chemical Abstracts, vol. 122, No. 12 (1995-03-20), abs. no. 142531 (XP002070103) — the patent's sole non-patent citation.
• Disclosure: A Fujisawa "medicinal composition." I was unable to retrieve and verify the full disclosure text of this Japanese publication in this session (my targeted search returned no primary document for it), so I cannot state with confidence what vehicle it teaches. Given the assignee, date, and the fact that the examiner cited only its abstract, it most plausibly concerns an external/topical composition of the tricyclic compound.
• §102 assessment: I cannot responsibly assert an anticipation mapping without the disclosure text. If it discloses only a tricyclic compound with a solubilizer/base (as the family pattern suggests), it would, like references 1–2, fail to anticipate claim 1 for want of the dual-oil blend and aqueous hydrophilic vehicle. Flagged as unverified — recommend pulling the JP full text before relying on it. (Confidence: low on content; flagged explicitly.)

5 & 6. EP 0 753 297 A1 and its U.S. equivalent US 5,939,427

• Full citation: EP 0 753 297 A1, "Lotion," Fujisawa Pharmaceutical Co., Ltd.; priority 1993-06-08; published 1997-01-15. U.S. equivalent: US 5,939,427, "Lotion for FK 506," Kagayama et al.; PCT/JP94/00863 filed 1994-05-30 (U.S. Ser. No. 08/537,948 filed 1995-11-21); issued 1999-08-17. Corresponds to the WO 94/28894 lotion discussed in the background of the subject patent.
• Disclosure: A lotion comprising tricyclic compound (I) or its salt, a dissolution/absorption promoter, a liquid medium, and optionally an emulsifier and/or a thickening (rheology-modifying) agent. The patent's own background characterizes WO94/28894 as a lotion containing these components.
• §102 assessment: Discloses (A) tricyclic compound, a liquid medium (E), an optional emulsifier (≈C) and optional thickener (≈D). It does not disclose the specific (B) isopropyl myristate + diethyl sebacate combination, and a "lotion" is not the semi-solid hydrophilic cream of claim 1. No anticipation of claim 1 or its dependents. Note on dates: EP 0 753 297 published 1997-01-15, only ~5 weeks before the 1997-02-20 priority date (potential §102(a) art but not a §102(b) statutory bar); the U.S. patent US 5,939,427 issued after the priority date, so it is only available, if at all, as §102(e) art via its 1994-05-30 PCT filing. (Confidence: high on bibliographic data; medium-high on the anticipation conclusion.)

7. WO 96/13249 A1

• Full citation: WO 96/13249 A1, "Pharmaceutical compositions," Novartis AG; priority 1994-10-26; published 1996-05-09.
• Disclosure: A third-party (Novartis) PCT application directed to pharmaceutical compositions. Search results confirm this document cites EP 0 474 126 among its own references, placing it in the same topical-macrolide/immunosuppressant formulation space, but I did not retrieve its claims to confirm whether it discloses an oil blend, a surfactant class, or an aqueous hydrophilic vehicle for a tricyclic compound (I).
• §102 assessment: Because it is a third-party reference published ~9 months before the priority date, it is potentially §102(a)/(e) art if it discloses the claim-1 elements. On the present record I cannot conclude it anticipates any claim; the specific dual-oil limitation (B) appears nowhere in the search excerpts. Flagged: verify the WO 96/13249 claims before relying on it. (Confidence: low on content; flagged.)

Family citation: IE 66485 B1

• Full citation: IE 66485 B1, "Aqueous liquid composition for external use," Fujisawa; 1989-07-05; granted 1996-01-10.
• Relevance: This is listed under "Family Cites Families" (i.e., cited by members of this patent's family), not as a U.S. examiner citation. It describes an aqueous external composition of the tricyclic compound, making it conceptually relevant to the aqueous/hydrophilic aspect of claim 1.
• §102 assessment: As an aqueous external composition it may disclose (A) + (E) + possibly (C)/(D), but I have not verified a disclosure of the (B) isopropyl myristate + diethyl sebacate blend; on the available record it does not anticipate claim 1. (Confidence: medium.)

C. Bottom line

1. Most relevant prior art = the applicant's own earlier topical FK506 filings: EP 0 474 126 A1 / US 5,385,907 (ointment) and EP 0 753 297 A1 / US 5,939,427 (lotion). These supply the active ingredient (including FK506 by name), the topical-external-composition concept, a surfactant emulsifier, an optional thickener, and (in the ointment) an absorption promoter. They are the references against which claim 1's narrowing to the specific isopropyl-myristate + diethyl-sebacate oil pair and the four named surfactant classes buys novelty.

2. No cited reference appears to anticipate claim 1 under 35 U.S.C. §102. Each of the seven patent citations and the single non-patent citation lacks at least the (B) combination of isopropyl myristate and diethyl sebacate, and several also lack the aqueous hydrophilic semi-solid vehicle (references 1–4 are ointments, suspensions, or oral/ophthalmic forms). Since claims 2–8 all incorporate the full claim-1 composition, none of them is anticipated by these references either. The cited art functions as §103 obviousness art, not §102 anticipation art.

3. Independent process claim 9 (and claim 10) recites mixing a drug/oil/surfactant solution with water to form an emulsion, then combining with a hydrophilic substance. The cited references do not disclose this ordered emulsion-then-thickener process, so claim 9 is likewise not anticipated.

4. Verification gaps I am flagging rather than papering over: (i) the full disclosure of JP H06-183970 A could not be retrieved; (ii) the claims of WO 96/13249 A1 were not retrieved. Both conclusions above are therefore provisional as to those two references. A definitive §102 determination would require the primary documents and the file wrapper (including any 2003 certificate of correction, per the record).

5. Confidence statement. Bibliographic data, dates, and assignees are high-confidence (from the authoritative patent text and corroborating records). The anticipation conclusions are medium-high and rest on the cited references as characterized; they are explicitly not a substitute for reading each reference's full claims and specification against each claim limitation.

I'll ground this analysis in the specific prior-art references listed on the patent's page, then build the § 103 combinations. Let me pull details on those references.

Let me confirm the specific oil/surfactant disclosures in EP0474126 and US5368865, since they anchor the key claim-1 element (the oil blend).

Obviousness Analysis — U.S. Patent No. 6,387,918 under 35 U.S.C. § 103

Scope note. This analysis uses the prior-art references listed in the "Prior Art" section of the US6387918 Google Patents page (the Citations (5), Patent Citations (7), and Non-Patent Citations (1) tables), plus the background references the specification itself identifies (JP H1‑157913, JP H5‑17481, WO94/28894). I could not independently retrieve the full text of US5368865A within my search budget; I flag where that reference's contribution is asserted rather than verified. Where the page lists an EP and its US counterpart as separate citations (e.g., EP0474126A1 / US5385907A; EP0753297A1 / US5939427A), I treat each literally as listed but note the family relationship.

1. The § 103 framework and the "actual differences"

The claim is a composition claim with a preamble that carries no patentable weight beyond the body. Under Graham v. John Deere and KSR Int'l v. Teleflex (550 U.S. 398 (2007)), the analysis turns on (a) the scope/content of the prior art, (b) the differences between the claim and the art, (c) PHOSITA level, and (d) secondary considerations.

PHOSITA: a formulator with a B.S./Ph.D. in pharmaceutics or pharmacy and several years' experience developing topical dermatological formulations (emulsions, gels, creams), familiar with the Handbook of Pharmaceutical Excipients and the standard nonionic-surfactant taxonomy.

The claim-1 elements and what is genuinely new. Elements (A) the tricyclic/FK506 genus, (D) a "hydrophilic substance," (E) water, and (F) optional pH agent were all squarely known in the FK506 topical art by 1997. The only candidate points of novelty are:

1. (B) the oil substance being a specific combination of isopropyl myristate + diethyl sebacate (rather than a single oil or another listed oil); and
2. (C) the surfactant being one of four named nonionic classes (polyoxyethylene alkyl ether; polyoxyethylene sorbitan fatty acid ester; pentaglycerol fatty acid ester; glycerol fatty acid ester).

Everything else is admitted prior art from the applicants' own earlier Fujisawa filings. The § 103 question therefore collapses to whether selecting these particular oils and surfactants was within the ordinary skill of a formulator facing a known problem.

2. The prior art of record

The critical observation: three of these references are the applicants' own earlier Fujisawa applications, and two of them (EP0474126 and EP0753297) already name diethyl sebacate and isopropyl myristate by name as the FK506 solubilizer/absorption promoter.

3. Combinations that render claim 1 obvious

Combination A (primary): US5939427 / EP0753297 (lotion) + WO1996013249 (Novartis emulsion) + US5385907/EP0474126 (ointment)

Element-by-element:

• (A) tricyclic (I) / FK506 — disclosed in all three.
• (B) isopropyl myristate + diethyl sebacate — both are expressly named, individually, as the solubilizing/absorption promoter in US5939427 (claims 1, 12, 13) and fall within the promoter Markush of US5385907/EP0474126 ("alkane dicarboxylic esters… diethyl sebacate"; "higher alkane carboxylic alkyl esters… isopropyl myristate"). Selecting two known, individually enumerated absorption promoters from the same short list, and using them together, is routine optimization of a result‑effective variable (In re Applied Materials, 692 F.3d 1289 (Fed. Cir. 2012); KSR). The '918 specification's own rationale — a monohydric‑alcohol fatty‑acid ester plus a dibasic‑acid diester in ~1:1 w/w — is an explanation of why the known pair works, not a new discovery.
• (C) four surfactant classes — US5939427 claim 8 recites nonionic surface‑active agents as the emulsifier; WO1996013249 lists polyoxyethylene sorbitan fatty‑acid esters (Tween 60/80) and polyoxyethylene fatty‑acid esters; JPH06183970A uses an emulsifier in an O/W system. Glycerol and pentaglycerol fatty‑acid esters are the textbook nonionic emulsifier classes for oil‑in‑water creams. Choosing an HLB ≥ 10 nonionic emulsifier (the '918 spec's own stated criterion) from the known set is routine.
• (D) hydrophilic substance — US5939427 claim 10 ("viscosity increasing agent is carboxypolymethylene"); EP0753297 claim 10 equivalent; WO94/28894 "thickening (rheology modifier)." Claim 4 of the '918 patent (carboxyvinyl polymer = Carbopol) maps directly onto this.
• (E) water — WO1996013249 expressly supplies a water‑containing FK506 emulsion; US5939427 supplies a "water‑miscible liquid medium."
• (F) optional pH control agent — neutralizing a carboxyvinyl polymer with NaOH to gel it is a routine, well‑known processing step (indeed the '918 spec calls pH adjustment a "safety" measure, not an inventive one).

Motivation to combine. Two independent motivations are express in the art:

(i) WO1996013249 supplies the reason to move from an oil‑based ointment to a water‑containing emulsion — it states that EP0474126's FK506 ointments "are oil based compositions and do not contain water," and that emulsions "are much less occlusive than oil‑based compositions and hence are better tolerated in many situations." That is a direct, articulated motivation to add water and an emulsifier to an FK506 vehicle — precisely the '918 patent's self‑described advance ("hydrophilic semi‑solid composition for external use").

(ii) US5939427 (and WO94/28894) supplies the reason to include a thickener: it discloses the FK506 lotion with an optional emulsifier and/or viscosity‑increasing agent, and the '918 spec itself explains the motivation ("different dosage forms suited to different clinical manifestations and different application sites are being demanded"; a lotion is thin and runs off, so thickening it into a semi‑solid is the obvious next step).

Combining a known FK506 lotion (US5939427), which already contains water, an emulsifier option, a carboxypolymer thickener option, and the two named oils, with the known teaching that aqueous FK506 emulsions are better tolerated (WO1996013249), yields every element of claim 1. Nothing in the art "teaches away"; the references point the same direction.

Combination B: US5385907/EP0474126 (ointment) + JPH06183970A (O/W emulsion) + US5939427 (lotion)

• US5385907/EP0474126 provides the tricyclic (I), the absorption‑promoter concept, and — critically — diethyl sebacate (Example 5) and isopropyl myristate (expressly, in the Markush).
• JPH06183970A provides the oil‑in‑water emulsion architecture: tricyclic solution + emulsifier (lecithin) + oily ingredient + water (+ glycerin as the hydrophilic/co‑solvent phase). This is the "surfactant + water + hydrophilic substance" triad of claim 1.
• US5939427 provides the carboxypolymethylene thickener and the same two oils.
• Motivation: JPH06183970A is by the same applicant (Fujisawa) addressing the same drug class and the same problem — formulating a poorly water‑soluble, unstable macrolide for administration with improved compatibility and stability. A formulator seeking a spreadable, non‑greasy, stable FK506 cream would combine the ointment's proven drug‑solubilizing oil system with the emulsion architecture taught by JPH06183970A, and thicken with the carboxypolymer of US5939427. That is a finite, enumerated set of known options with a reasonable expectation of success, the hallmark of obviousness (KSR; In re Kubin, 561 F.3d 1351 (Fed. Cir. 2009)).

Combination C (aggregate): WO1996013249 + US5939427 + JPH06183970A

Even standing alone, WO1996013249 (aqueous FK506 emulsion, Tween‑class emulsifiers, water) plus US5939427 (the two oils + carboxypolymethylene thickener) reaches claim 1. JPH06183970A merely reinforces the O/W‑emulsion‑with‑surfactant teaching.

Combining two known, individually enumerated oils is not an inventive combination. KSR specifically approved "combining two disclosed elements to achieve a predictable result" where the combination does no more than each does separately. Here the two oils are the same functional class recited in the same Markush group of the same prior Fujisawa filings; their combination yields a vehicle with predictable solubilization/absorption properties.

4. Dependent claims

• Claim 2 (amounts: surfactant 0.1–15%, oil 2–50%, hydrophilic 0.1–10%): Ranges overlap those disclosed in the art — US5385907/EP0474126 recite tricyclic 0.01–10% w/w and promoter 1–30% w/w; US5939427 recites FK506 0.01–10% and promoter 1–30% w/w. Optimizing excipient ranges is routine (In re Aller; In re Woodruff). Obvious.
• Claim 3 (pH 3.5–6) / Claim 8 (pH ~4–5): Adjusting the pH of an aqueous topical cream — particularly a carboxyvinyl‑polymer gel, which requires acidic‑to‑slightly‑acidic pH to gel and to match skin pH — is a routine formulation parameter. The '918 spec itself frames the pH agent as a "safety," not novelty, feature. Obvious.
• Claim 4 (carboxyvinyl polymer): Anticipated/obvious over US5939427 claim 10 ("carboxypolymethylene"). Obvious.
• Claim 5 (polyoxyethylene sorbitan fatty acid ester): Disclosed as an emulsifier in WO1996013249 (Tween 60/80 = POE‑20 sorbitan monostearate/monooleate) and within US5939427 claim 8 (nonionic surfactants). Obvious.
• Claim 6 (narrowed Formula (I) substituents): The narrowed genus reads on FK506 itself, disclosed in every reference. Obvious.
• Claim 7 (FK506 specifically): FK506 is the exemplified, named compound in US5385907 (Example 5), US5939427, and EP0474126. Obvious (indeed, arguably anticipated in a genus that expressly names it).

5. Process claims 9 and 10

Claim 9 (make the solution of drug + oil + surfactant, combine with water to form an emulsion, then mix with the hydrophilic substance) and claim 10 (premix the hydrophilic substance/pH agent with water, then combine with the emulsion) recite conventional emulsion‑manufacturing steps:

• JPH06183970A teaches combining a tricyclic solution with an oil‑in‑water emulsion — i.e., making the drug/oil solution, emulsifying with an aqueous phase, and combining phases.
• US5385907 Example 1 teaches dissolving FK506 in the promoter at ~70 °C, combining with a heated base, homogenizing with a homomixer, and cooling — the same "heat, homogenize, cool" sequence the '918 spec uses (60–80 °C, cool to ~30 °C).
• US5939427/WO94/28894 teach adding an emulsifier and/or thickener to the FK506 system.

A process that applies known mixing/emulsification/thickening steps in a known order to the known ingredients of claim 1 is obvious, and its obviousness follows from that of the composition (In re Kalm, 378 F.2d 959 (CCPA 1967)). The claim‑10 "premix the thickener with water" variant is the ordinary way one hydrates a carboxyvinyl polymer; no unexpected result is asserted.

6. Secondary considerations / rebuttal evidence

For the § 103 conclusion to be overcome, the patentee would need unexpected results or other objective indicia with a nexus to the claimed combination. The intrinsic record is weak on this point:

• Table 1 reports only "AUC[0–24 hr] > 30 ng·hr/mL" for every tested formulation (2, 3, 7, 12, 20) — a single censored threshold value, with no comparative arm against the closest prior art (the US5939427 lotion or the US5385907 ointment). A result common to all tested formulations, and not compared to the prior art, cannot establish that the specific isopropyl‑myristate/diethyl‑sebacate blend or the specific surfactant classes produce an unexpected effect. There is no nexus between the claimed selection and any demonstrated superiority.
• The specification's stated advantages (stability, absorbability, low irritation) are the same advantages the prior art already claimed for its own FK506 formulations — US5385907 ("stable and exerts excellent absorbency"), US5939427 ("stable and excellent in absorption… scarcely irritates the skin"), and WO1996013249 ("better tolerated"). Where the asserted advantage is coextensive with the prior art's own stated advantages, it is not evidence of non‑obviousness.
• Common ownership / near‑simultaneous art cuts against patentability here: the closest references are the applicant's own earlier Fujisawa filings, and Fujisawa's own later filings (e.g., WO02/096419, the gel; and the "binary system of isopropyl myristate and diethyl sebacate" example in the CN1537003A family) show the oil pair was treated as an ordinary formulatory choice across the same program, not an unexpected discovery.

Accordingly, on this record the objective indicia do not rebut the prima facie case.

7. Conclusion

Claim 1, and all claims depending from it, are obvious under § 103(a) as a matter of the prior art of record. The strongest single combination is:

US5939427 / EP0753297 (Fujisawa FK506 lotion — discloses both diethyl sebacate and isopropyl myristate as the solubilizer/absorption promoter, a water‑miscible medium, and optional emulsifier + carboxypolymethylene thickener) in view of WO1996013249 (Novartis — teaches that a water‑containing FK506 emulsion is less occlusive and better tolerated than oil‑based compositions, and lists Tween‑type POE‑sorbitan emulsifiers) and, optionally, US5385907 / EP0474126 (the FK506 ointment naming diethyl sebacate and isopropyl myristate and their Markush classes) and JPH06183970A (the FK506 O/W‑emulsion system with emulsifier + water + glycerin).

The motivation is articulated in the art itself (add water/emulsifier to improve tolerability; thicken the lotion to make a semi‑solid for different application sites), the oil pair and surfactant classes are drawn from short, enumerated lists of known equivalents already used with the same drug, and the objective evidence of record is too weak (single censored data point, no comparative arm, no nexus) to rebut the conclusion. Claims 2–10 fall with claim 1: they recite routine excipient ranges, pH adjustment, known selected materials (carboxypolymer, POE‑sorbitan esters, FK506), or conventional emulsion‑making steps.

Caveats / limitations. (i) This is an obviousness analysis, not an invalidity holding; a full § 103 record would require the complete texts and effective dates of each reference (all listed references predate the 1997‑02‑20 priority date, which I assume but did not independently re‑verify for each). (ii) I did not retrieve the full text of US5368865A, so I have not relied on it as a primary reference. (iii) Whether a given secondary reference is analogous art is straightforward here — all are topical macrolide/FK506 formulation references in the same field of endeavor, so the analogous‑art test (In re Bigio, 381 F.3d 1320 (Fed. Cir. 2004)) is satisfied.