US 6420399

I'll search for authoritative information on US patent 6420399 and check for any CAFC litigation.

Let me search specifically for litigation and CAFC involvement for US 6,420,399.

US Patent 6,420,399 B1 — Analyst Summary

Sourcing note: My searches hit Google Patents (which mirrors USPTO full-text/assignment data), FreePatentsOnline, and the USPTO-hosted patentimages PDF. I did not obtain a direct USPTO PatentCenter/PAIR record, and I found no CAFC 2026 docket (or any Federal Circuit or district-court record) in which U.S. 6,420,399 is an asserted, challenged, or appealed patent. Treat "no litigation found" as a negative search result, not affirmative proof of absence. Separately, be aware the bare string "6420399" also matches an unrelated Japanese patent, JP 6420399 B1 (FANUC, converter power-element fault detection, issued 2018-11-07) — that is a different patent in a different jurisdiction and must not be conflated with US 6,420,399.

Bibliographic data

Abstract (as issued)

Topical ophthalmic anti-allergy drugs are identified by the extent of their interaction with a phospholipid model membrane. Disclosed are topically administrable ophthalmic formulations containing amphipathic anti-allergy compounds at concentrations such that the drugs have Surface Activity Ratings from about 2–11.

Independent claim 1 — plain language

The patent has exactly one independent claim, drafted in "improvement" (Jepson-style) form:

Claim 1: In a topically administrable ophthalmic pharmaceutical composition containing an ophthalmically acceptable, amphipathic antihistamine drug at a concentration of about 20 mM or less, the improvement is that the drug concentration is selected so the drug has a Surface Activity Rating of about 2–11, with a negative proviso that the drug is not olopatadine, ketotifen, emedastine, pheniramine, pyrilamine, cromolyn, nedocromil, or levocabastine.

In plain terms: this claim covers an eye-drop-type composition built around a lipid-interface-active antihistamine, where the amount of drug is the distinguishing feature — the concentration must be set so the molecule's measured penetration of a phospholipid monolayer (the "Surface Activity Rating," Δπ in mN/m) stays within 2–11 mN/m, and the total drug load must be ≤ about 20 mM. The eight named drugs are carved out of the claim.

Dependent claim 2: Same composition, but the Surface Activity Rating is narrowed to 4–11 mN/m.

What the "Surface Activity Rating" is (specification, not claim)

• Measured by Δπ (mN/m) of a monomolecular SOPC (1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine) film on an aqueous sub-phase in a modified Langmuir trough, at an initial surface pressure of 28–32 mN/m (chosen to mimic mammalian cell membranes), 24 °C, HEPES/NaCl buffer pH 7.5.
• Drug is introduced by continuous sub-phase exchange at ~0.4 mL/min so the monolayer is not disturbed; concentration ramped from 0 to ≥5 mM (preferably ≥20 mM, or the solubility limit).
• Example 3 reports olopatadine SAR = 7.1 mN/m (0–5 mM) and ketotifen SAR = 15 mN/m (0–3.5 mM).
• Stated rationale: compounds with an SAR > 11 are "likely to cause mast cell membrane instability and leakage of autocoids, including histamine, from human conjunctival mast cells."

Points of technical/practical interest (analyst observations, not claim language)

1. The claim is a composition claim, not a method claim. The Summary of the Invention describes "a method for selecting anti-allergy drug concentrations," but no method of selection or method of treatment was issued; only the composition (and its narrower dependent) issued.
2. Internal tension worth flagging: the two compounds used to demonstrate the method in Example 3 — olopatadine (SAR 7.1, inside the 2–11 window) and ketotifen (SAR 15, outside it) — are both expressly excluded from claim 1 by the proviso, as are the other named ocular anti-allergy agents of the era. The worked example thus illustrates the metric using compounds the claims cannot cover.
3. The proviso is a negative limitation, effectively reserving the metric itself while excluding the specific prior-art/known commercial actives.
4. Prior art cited by the examiner includes US 4,871,865 and US 4,923,892 (Burroughs Wellcome, doxepin carboxylic acid derivatives as mast cell stabilizers with antihistamine action), US 5,641,805 (Alcon — topical ophthalmic olopatadine formulations), US 4,778,814 (Ciba-Geigy), US 5,192,780 (Alcon), and non-patent literature on antihistamine/lecithin monolayer surface activity (Attwood et al.), mast-cell biphasic histamine release (Mota et al.), and the Wilhelmy-method instrumentation (Tsujita et al.; Momsen et al.).
5. Litigation context caution: the well-known olopatadine patent litigation (e.g., Alcon v. Apotex, N.D. Ind. — cited in my search results, addressing the '805 patent, US 5,641,805, and human conjunctival mast cell written-description issues) concerns a different patent, not US 6,420,399. Likewise, the Neev v. Alcon judgment I encountered involved US 6,482,199 — a different number. Do not map those proceedings onto '399.

Explicit uncertainties / limits on this summary

• USPTO direct-record verification: I relied on Google Patents' reproduction of USPTO data and the issued-patent PDF, not a live USPTO PatentCenter query. Claim text, dates, inventorship, and the assignment chain are, however, internally consistent across the patent PDF, Google Patents, and FreePatentsOnline.
• Expiration: the "Expired – Lifetime" status with a 2020-03-16 anticipated expiration is a computed/assumed legal status (Google Patents explicitly labels legal status as an assumption). A USPTO maintenance-fee/expiration record would be needed to state this as a legal conclusion; note the last recorded maintenance-fee payment in the data I retrieved was the 12-year fee (2013-12-18), and no later payment events appear.
• CAFC 2026 dockets: my targeted searches for a Federal Circuit 2026 appeal involving 6,420,399 returned nothing relevant. I cannot rule out a docket that is not publicly indexed by the search tools I used; this should be confirmed against the CAFC docket system and PACER/Reuters if certification is required.
• Foreign counterparts: EP 1187617 B1 is titled "Method for selecting the concentration of an amphipathic antihistamine drug by determining the drug's surface activity rating," i.e., the European family member appears method-oriented, whereas the US claim as issued is composition-oriented. I did not verify the EP claims directly.
• Identifier discipline: all alphanumeric identifiers above are reproduced exactly as found; where "6420399" appears in another jurisdiction (JP 6420399 B1) it denotes an unrelated invention.

I'll search for litigation involving US patent 6420399.

Let me search litigation-specific databases.

Let me check dedicated litigation databases directly.

Litigation Search Report — U.S. Patent No. 6,420,399

Bottom line

I found no evidence of any litigation involving U.S. Patent No. 6,420,399 in any U.S. district court, the Federal Circuit, or the ITC. On the record available to me, no known litigation exists for this specific patent.

Patent identification (as verified, interpreted literally)

• Patent: US 6,420,399 B1 — "Topical ophthalmic mast cell stabilizers for treating allergic eye disease"
• Inventors: Gustav Graff; John M. Yanni
• Original assignee: Alcon Manufacturing Ltd (now Alcon Research LLC)
• Application: US 09/527,401; filed 2000-03-16; priority 1999-06-18
• Granted: 2002-07-16
• Status: Expired – Lifetime; anticipated expiration 2020-03-16
• Claims: 2 (both directed to a topically administrable ophthalmic composition with an amphipathic antihistamine drug having a Surface Activity Rating of about 2–11, expressly excluding olopatadine, ketotifen, emedastine, pheniramine, pyrilamine, cromolyn, nedocromil, and levocabastine)

Searches performed and what they returned

1. General web search for "6420399" litigation / patent lawsuit — Returned only the patent's own prosecution/assignment record and unrelated hits. Notably, several hits were for different patents entirely that share the digit string:
   • JP 6420399 B1 (Japanese patent, Fanuc, a power-converter fault-detection device) — a Japanese patent, not the US patent.
   • US 6,440,399 B1 — a different US patent (a family-member listing artifact), not US 6,420,399.
   • JP 6420399 / US 6,420,399 were also surfaced in the "similar documents"/citation-table context of other Alcon and J&J patents, which is citation noise, not litigation.
     I did not treat any of these as litigation against US 6,420,399.
2. Unified Patents litigation portal query — No docket or case list for 6420399 was returned.
3. CourtListener / RECAP (PACER-derived) query — No docket, opinion, or filing referencing patent 6,420,399 was returned.
4. Docket Alarm / general docket query — No results for this patent number.
5. Google Patents record review — The US 6,420,399 record shows a full prosecution, assignment, and fee-payment history, and no litigation docket section, which is consistent with zero asserted cases.

Important caveats (please read)

• Search-result caveat under your strict-ID rule: Because a string search for "6420399" returns the Japanese patent JP 6420399 B1 and US 6,440,399, it is easy to conflate them. I have deliberately not auto-corrected and have excluded those from this report, since they are not US 6,420,399.
• Confidence level: I have low-to-moderate confidence in the completeness of this negative result. CourtListener's RECAP corpus is incomplete (it depends on PACER documents being pulled by users/volunteers), and my searches of the Unified Patents portal were indirect (web search rather than live navigation of every docket list). A truly exhaustive check would require a full-text Westlaw/Lexis KeyCite or Lexis CourtLink search of the patent number, which I cannot run here.
• Procedural vs. litigation matters are different. I found no litigation. I did not find evidence of, and am not asserting, any U.S. post-grant proceeding (IPR/PGR) or reexamination for this patent. Note separately that this patent has a European family member, EP 1 187 617 B1, whose title ("Method for selecting the concentration of an amphipathic antihistamine drug by determining the drug's surface activity rating") indicates the same subject matter; European opposition/appeal activity, if any, is an EPO proceeding and not U.S. litigation, and I have no confirmation of one.
• Why zero litigation is plausible: The patent expired on its 20-year term on 2020-03-16, and it is a narrow, method-oriented selection patent (2 claims with an express carve-out of the principal commercial drugs, including olopatadine—Alcon's own PATANOL® active). Damages exposure was therefore limited and short-windowed, reducing the likelihood of any assertion suit.

Recommended next steps to firm up the negative result

1. Run a KeyCite / Westlaw "Litigation History" lookup on 6,420,399.
2. Run a Lexis CourtLink / Docket Navigator search on the patent number.
3. Manually browse https://portal.unifiedpatents.com/litigation/caselist and search Docket Navigator's patent profile for 6,420,399.
4. Verify the EPO Register for EP 1 187 617 for any opposition/appeal (distinct from US litigation).

If you'd like, I can attempt to re-verify against a specific database once the search budget resets, or draft a formal "no known litigation" declaration suitable for a Privilege/Invalidity or FTO memorandum.

I'll verify the structured data against live sources before writing anything.

Let me run more targeted searches on this specific patent number and related litigation.

Let me confirm with a couple more targeted checks before concluding.

Proceedings overview

Total AIA trial proceedings on US 6,420,399: 0 (zero). The USPTO Open Data Portal returns no IPR, PGR, or CBM proceeding naming this patent, and independent web searches surfaced no petition, institution decision, or Final Written Decision directed to the '399 patent. The breakdown is therefore 0 active / 0 claims invalidated / 0 claims sustained / 0 settled / 0 institution denials, and the defensive posture is unusual: this is an expired patent that was never PTAB-tested, so there is no invalidation record to leverage — but there is also nothing to fear prospectively. US 6,420,399 issued 2002-07-16, and Google Patents records its anticipated expiration as 2020-03-16 (20 years from the 2000-03-16 filing date).

Because there are no proceedings to list, the per-proceeding template is not populated. What follows is the negative finding, the evidence behind it, and the related-family activity that a defendant will inevitably encounter if they confuse this patent with Alcon's olopatadine litigation asserts.

No AIA trial proceedings on file — verification

• Structured source (canonical): The USPTO ODP "PTAB proceedings on file" block for US 6,420,399 is empty. No trial numbers, no petitioner names, no statuses.
• Independent web check (2026-10-01): Searches for IPR/PGR/CBM petitions tied to "6,420,399," to Alcon Research / Alcon Manufacturing as patent owner, and to the Graff & Yanni inventorship returned only (a) the patent's own Google Patents / FreePatentsOnline pages, (b) district court decisions on other patents, and (c) PTAB petitions against US 8,791,154 (a later, different olopatadine patent). Nothing pointed to a trial on the '399 patent.
• Caveat: I cannot prove a negative by search. The ODP block is the authoritative signal, and it is empty; if a 2012–2020-era petition existed, it is now closed and would ordinarily still be indexed. Treat "no AIA proceedings" as high-confidence but not infallible, and re-verify at PTAB E2E (https://ptacts.uspto.gov) and via the patent's PTAB trial page (https://patents.google.com/patent/[US6420399B1](/patent/US6420399B1)/en) before relying on it in a filing.

Claims status (as issued; never PTAB-amended)

• Claim 1 — UNTESTED. The sole independent claim; a "composition" claim in Jepson-style improvement format: a topically administrable ophthalmic composition comprising an ophthalmically acceptable, amphipathic, antihistamine drug at ≤ about 20 mM, wherein the drug concentration is such that the drug has a Surface Activity Rating from about 2–11, with the proviso excluding olopatadine, ketotifen, emedastine, pheniramine, pyrilamine, cromolyn, nedocromil, and levocabastine.
• Claim 2 — UNTESTED. Depends from claim 1; narrows the Surface Activity Rating to 4–11.

No claim was canceled, confirmed, or amended under 35 U.S.C. §§ 316(d)/318(b). There is no certificate to check.

Related-family activity (NOT proceedings on the '399 patent — do not conflate)

A defendant researching "Alcon + olopatadine + PTAB" will land on these. They concern different patents, and § 315(e)(2) estoppel from them does not run against the '399 patent.

• IPR2016-00544 — Argentum Pharmaceuticals LLC v. Alcon Research, Ltd. (filed 2016-02-02). Challenged US 8,791,154 ("High concentration olopatadine ophthalmic composition"), not the '399 patent. Petitioner asserted § 103 grounds over Bhowmick (WO 2008/015695) in view of Yanni and Castillo, and over Schneider in view of Hayakawa, Bhowmick, and Castillo. See the petition at Docket Alarm: https://www.docketalarm.com/cases/PTAB/IPR2016-00544/. Source for filing metadata: https://natlawreview.com/node/58092/printable/pdf
• IPR2016-01640 — Apotex Inc. v. Alcon Research, Ltd. Same '154 patent, same core grounds (§ 103 over Bhowmick + Yanni + Castillo). Petition: http://patentdocs.typepad.com/files/apotex-ipr2016-01640-petition.pdf
• IPR2018-01020 — Argentum Pharmaceuticals LLC v. Alcon Research, Ltd. ('154 patent; Argentum exhibit referencing the earlier proceeding: https://www.docketalarm.com/cases/PTAB/IPR2018-01020/)

Why this matters and why it doesn't: these show Alcon's olopatadine portfolio was actively challenged and litigated — indeed, the relevant prior art (Yanni et al., J. Ocular Pharmacol. Ther. 12:389-400 (1996)) is cited in the '399 patent's own "Non-Patent Citations" list and is the very reference the later petitioners used. But none of that reach-back touches the '399 patent's claims, and none of those petitioners is estopped as to it.

Parallel district court activity (also not this patent): Alcon Research, Ltd. v. Apotex Inc., No. 1:06-cv-01642 (S.D. Ind.) — findings of fact and conclusions of law at https://www.courtlistener.com/docket/[4266333/333](https://assignmentcenter.uspto.gov/search/patent/reelFrameDetail?reelFrame=4266333-0333)/alcon-manufacturing-ltd-v-apotex-inc/ — and Alcon Research, Ltd. v. Watson Laboratories, Inc., No. 1:15-cv-01159 (D. Del.) — https://www.courtlistener.com/docket/[5175332/155](https://assignmentcenter.uspto.gov/search/patent/reelFrameDetail?reelFrame=5175332-0155)/alcon-research-ltd-v-watson-laboratories-inc/. Both centered on US 5,641,805 and US 8,791,154. On appeal, the Federal Circuit reversed the non-obviousness holding as to six claims of the '805 patent while affirming two narrower dependent claims (Alcon Research, Ltd. v. Apotex Inc., Fed. Cir. 2012 — summary at https://patentdocs.org/2012/08/12/alcon-research-ltd-v-apotex-inc-fed-cir-2012/). I found no reported decision or docket entry asserting US 6,420,399 itself.

Strategic summary

Claim status. The entire patent — claim 1 and claim 2 — is UNTESTED at the PTAB. Nothing is canceled, nothing is confirmed, nothing is amended. That cuts both ways: there is no favorable FWD to hand a judge, but there is also no adverse claim-construction or invalidity ruling binding anyone under § 315(e)(1)/(2).

Estoppel landscape. Because no IPR or PGR ever instituted on this patent, there is zero § 315(e)(2) estoppel applicable to US 6,420,399. Any defendant is free to run the full menu — §§ 102 and 103 over any patents and printed publications, § 112 written description / enablement / indefiniteness (note that § 112 is not available in an IPR, so a district court or ITC forum is the only place it lives), and prior public use or on-sale art under § 102(a)(1) that IPR cannot reach. No petitioner is barred, and no privy of any petitioner is barred.

Pattern signals. No defensive aggregator (Unified Patents, RPX, etc.) appears anywhere in this patent's chain — consistent with a zero-proceeding history. On the patent-owner side, Alcon is demonstrably willing to litigate its olopatadine rights to judgment and through appeal (the '805 appeal above), and it does not appear to have used IPR offensively against competitors on this patent. There is no repeat-petitioner pattern directed at the '399 patent.

The real signal is expiration, not litigation. US 6,420,399 is recorded as Expired – Lifetime with an anticipated expiration of 2020-03-16. Any live assertion of this patent today would have to be a claim for pre-expiration damages for acts occurring on or before that date. That is a narrow, backward-looking posture. It also explains the absence of IPRs: by the time AIA trials were widely used (2013 onward), the patent had roughly seven years of enforceable term left, its independent claim was already narrow and proviso-limited, and the commercially attractive olopatadine targets were captured by later Alcon patents (the '154 patent) worth attacking instead.

Recommended next steps

• If you are a defendant: confirm the expiration date and term. Pull the front page of US 6,420,399 and the USPTO Patent Center record (https://patentcenter.uspto.gov) to verify the 2020-03-16 expiration and check for any terminal disclaimer, PTA, or extension that could shift it. If the patent is expired and the demand letter asserts ongoing infringement, that is a threshold defense independent of validity.
• Because there is no PTAB record, you have full freedom of grounds. Prioritize (i) § 103 over Yanni 1996 (already of-record and the workhorse in the '154 IPRs) combined with a surface-activity/physical-chemistry reference, and (ii) invalidity theories that only a district court can hear — § 112 written description and enablement of the "Surface Activity Rating" limitation, which is defined only by a bench protocol in the specification (SOPC monolayer at 28–32 mN/m, 24 °C, 0.4 mL/min sub-phase exchange) and may raise indefiniteness or enablement questions at the boundary values (2 and 11 mN/m).
• Do not cite the '154 IPRs as if they decided anything about this patent. They did not. Any estoppel, claim construction, or invalidity finding from IPR2016-00544, IPR2016-01640, or IPR2018-01020 is limited to US 8,791,154. If opposing counsel conflates the two, that is a correctable misstatement — and an opportunity.
• Re-verify before filing. Re-run the ODP query and check PTAB E2E (https://ptacts.uspto.gov) plus CourtListener (https://www.courtlistener.com) for any newly indexed proceeding or CAFC appeal, since my search is a point-in-time check dated 2026-10-01.

I could not verify any judge panel, institution decision, FWD, settlement, or Federal Circuit appeal for this patent because none exists on the record I was able to access. Nothing above should be read as a representation that a proceeding was filed and hidden — the evidence is the opposite: no proceeding was filed.

I have the core legal-events data from the Google Patents mirror of the USPTO record. Let me try to pull additional assignment-level detail (correspondent of record, execution dates) directly before writing up.

Assignment & Ownership Reconstruction — US 6,420,399 B1

Source note: The USPTO Assignment Center (https://assignmentcenter.uspto.gov/) and its legacy mirror (https://assignment.uspto.gov/patent/index.html) are interactive query surfaces that my search tooling cannot navigate directly; I could not load a live Patent Assignment Search result page for this patent. The assignment data below is therefore taken from the Google Patents legal-events table, which reproduces USPTO assignment records (reel/frame, conveyance text, execution/"effective" dates, recording dates, assignor/assignee). I retrieved three recorded post-filing assignment events with reel/frame numbers. The correspondent-of-record field was NOT present in the data I could retrieve — I flag that explicitly below rather than inferring it. Verify at the Assignment Center link in the Verdict section.

Inventors

Unusual-pattern check — no red flags. There is no evidence of inventors departing Alcon within 12 months of filing. To the contrary, both Graff and Yanni appear as named inventors on later Alcon-assigned applications, and Yanni's inventor record runs for many years after the 1999 priority date. This is the opposite of the "inventors bail out early → portfolio fire-sale" precursor. The only "unusual" feature is structural, not personnel-based: the application claims priority from two provisionals (60/139,945 filed 1999-06-18 and 60/158,177 filed 1999-10-07) that share the same June 1999 priority family.

Original assignee

• Entity named on the issued patent: Alcon Manufacturing, Ltd. (Fort Worth, TX). The inventors first assigned to Alcon Laboratories, Inc., which then assigned onward to Alcon Manufacturing, Ltd. before the patent issued — so the "original assignee" as printed on the face of US 6,420,399 is Alcon Manufacturing, Ltd.
• Primary line of business: ophthalmic pharmaceuticals and surgical/vision-care products — the Alcon group (ophthalmic anti-allergy drops, glaucoma agents, surgical devices, contact-lens care). Alcon is one of the largest pure-play eye-care companies globally.
• Did they ship a product embodying the claims? Effectively no — and this is the analytically important point. Alcon's commercial ophthalmic anti-allergy franchise is olopatadine (Patanol 0.1%, Pataday 0.2%, both moved OTC in 2020). Olopatadine is one of the eight drugs expressly carved out of claim 1 by the negative proviso. The patent is a selection patent over non-olopatadine amphipathic antihistamines with a Surface Activity Rating of 2–11; the claims cover no identified Alcon commercial product. (This mirrors the analyst-flagged tension in the earlier summary: the two drugs used to demonstrate the metric in Example 3 — olopatadine and ketotifen — are both excluded from the claims.)
• Current status: Operating. The chain's terminal assignee listed by Google Patents is Alcon Research LLC. Alcon was controlled by Novartis (staged acquisition completed April 2011) and was spun off as an independent, publicly traded company, Alcon Inc. (NYSE: ALC), in April 2019. Alcon Research LLC/Alcon Inc. is a going concern — no bankruptcy, no dissolution. The Australian official journal records mass assignments "Alcon Research, Ltd. → Alcon Inc." for the foreign family around 2020, but the US ownership chain I can see stops at Alcon Research, Ltd. (2008); I did not find a discrete recorded US assignment moving '399 to "Alcon Research LLC." That Ltd.→LLC step may be a conversion/change-of-name recorded outside the events I retrieved — flagging as unclear rather than asserting it.

Assignment timeline

Chronological, as recorded (execution dates are the "effective date" fields from the assignment records; recording dates are the USPTO recordation dates):

1. 2000-03-15 (executed) / recorded 2000-03-16 — Reel 010688/0995

   • Conveyance: Assignment (of assignors' interest)
   • Assignor: Gustav Graff; John M. Yanni
   • Assignee: Alcon Laboratories, Inc. (Texas)
   • Correspondent: not present in the retrieved record — the only free-format text is "ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:GRAFF, GUSTAV;YANNI, JOHN M." The recording correspondent/attorney field was not exposed by the data source I could reach. (Circumstantial, not a finding: contemporaneous Alcon PCT filings such as WO 98/53862 name Patrick M. Ryan as correspondent, "Alcon Laboratories, Inc., R&D Counsel Q-148, 6201 South Freeway, Fort Worth, TX 76134-2099." That is prosecution-side counsel on a related case, not the '399 assignment correspondent — do not treat it as such.)
   • Context: Standard employee-inventor assignment to the employer — initial acquisition.

2. 2001-03-22 (executed) / recorded 2001-03-26 — Reel 011667/0559

   • Conveyance: Assignment
   • Assignor: Alcon Laboratories, Inc.
   • Assignee: Alcon Manufacturing, Ltd. (Texas)
   • Correspondent: not present in the retrieved record (free-format text: "ASSIGNMENT OF ASSIGNOR: ALCON LABORATORIES, INC.").
   • Context: Intra-group reorg — moving the application to the Alcon manufacturing/holding entity before grant.

3. 2008-01-01 (executed) / recorded 2008-07-21 — Reel 021266/0729

   • Conveyance: Merger (not a sale)
   • Assignor: Alcon Manufacturing, Ltd.
   • Assignee: Alcon Research, Ltd. (Texas)
   • Correspondent: not present in the retrieved record (free-format text: "MERGER;ASSIGNOR:ALCON MANUFACTURING, LTD.").
   • Context: Corporate merger / internal reorganization — the operating entity absorbed into Alcon Research, Ltd. The recording occurred ~6.5 months after the stated effective date, consistent with delayed recordation after a group restructuring.

No further US assignments are recorded in the events I retrieved. After 2008-07-21 the only events are statutory maintenance-fee payments (4-yr 2006-01-17; 8-yr 2010-01-19; 12-yr 2013-12-18) and the 2020-03-16 anticipated expiration. The 4-year fee postdates issue; the 8- and 12-year fees were paid by the then-owner.

Timeline diagram

timeline
    title Ownership of US 6420399
    1999 : Two provisionals filed
    2000 : Nonprovisional filed 16 March
         : Inventors assign to Alcon Laboratories
    2001 : Assigned to Alcon Manufacturing Ltd
    2002 : Patent issues 16 July
    2008 : Merger into Alcon Research Ltd
    2011 : Novartis completes acquisition of Alcon
    2019 : Alcon spins off from Novartis as ALC
    2020 : Patent expires 16 March

NPE / troll-pattern signals

Verdict

Defensive / non-asserting — (closest available category; see caveat).

Justification: The entire recorded chain is intra-corporate Alcon ownership: inventors → Alcon Laboratories, Inc. (reel 010688/0995, executed 2000-03-15), → Alcon Manufacturing, Ltd. (reel 011667/0559, executed 2001-03-22), → Alcon Research, Ltd. via merger (reel 021266/0729, executed 2008-01-01). There are zero shell-entity transfers, zero known asserters, zero cascading LLC hops, and zero transfers to the patent; the patent sat with the originating operating-company family until it expired on 2020-03-16. The claims carve out olopatadine — Alcon's own commercial molecule — so Alcon had little reason (and, as a selection claim over unspecified compounds, little ability) to assert '399, consistent with the observed non-assertion.

Caveat on the label: "Defensive / non-asserting" as defined in the taxonomy requires termination at a defensive aggregator (RPX/AST/LOT/Unified/OIN). That is not what happened here — the chain terminates at Alcon Research LLC, an operating eye-care company, not an aggregator. None of the five verdict categories maps cleanly onto "operating company retained ownership, never asserted, and the patent has now expired." I selected the closest fit rather than force an inaccurate "NPE" or "Operating-company assertion" label; the evidence affirmatively rules out any NPE pattern. If your taxonomy permits, the most precise characterization is "operating-company retention, non-asserting, expired."

Verification link: USPTO Patent Assignment Search — https://assignmentcenter.uspto.gov/ (search patent number 6,420,399). Cross-check reels 010688/0995, 011667/0559, 021266/0729 and pull the correspondent-of-record field that I could not retrieve here; if a Ltd.→LLC conversion record exists, it should appear as a change-of-name/conversion event.

Firm-up actions

1. Open the Assignment Center record for 6,420,399 and capture the correspondent/attorney on each of the three reels — that is the one field missing from my reconstruction.
2. Confirm whether a discrete Alcon Research, Ltd. → Alcon Research LLC conversion/change-of-name record exists (Google Patents lists the LLC as current assignee but exposes no such US event).
3. Confirm the 2020-03-16 expiration against the USPTO maintenance-fee record (the last fee event I saw was the 12-year payment on 2013-12-18; the next window would have been the 16-year/3.5-year pre-expiry payments, which do not appear in the retrieved events).

I'll verify the patent record and prior-art citations against live sources before mapping § 102 relevance.

Prior-Art Analysis — U.S. Patent No. 6,420,399 B1

Patent: US 6,420,399 B1 — "Topical ophthalmic mast cell stabilizers for treating allergic eye disease"
Inventors: Gustav Graff; John M. Yanni · App. No. 09/527,401 · Filed 2000-03-16 · Priority 1999-06-18 (Prov. 60/139,945) and 1999-10-07 (Prov. 60/158,177) · Issued 2002-07-16 · Assignee Alcon Manufacturing, Ltd. → Alcon Research LLC

Sourcing note / limits: I could not execute a fresh, direct USPTO PatentCenter/PAIR or PIAS query within this session (tool step limit reached). Accordingly, the prior-art list below is taken verbatim from the patent's own front-page "Patent Citations (10)" table in the authoritative full text supplied for US 6,420,399, with dates and descriptions cross-checked against Google Patents, FreePatentsOnline, the issued-patent PDFs, and (for the Bridge Pharma reference) the corresponding U.S. national-phase patent US 6,207,684 B1. Where a date could not be independently verified I flag it. I did not auto-correct any identifier.

1. The claims being measured against (recap, for § 102 mapping)

• Claim 1 (independent, Jepson form): In a topically administrable ophthalmic composition comprising an ophthalmically acceptable, amphipathic, antihistamine drug at a concentration of about 20 mM or less, the improvement wherein the drug concentration is such that the drug has a Surface Activity Rating (SAR) from about 2–11, provided the drug is not olopatadine, ketotifen, emedastine, pheniramine, pyrilamine, cromolyn, nedocromil, or levocabastine.
• Claim 2 (dependent): SAR 4–11.

For a § 102 anticipation, a single reference must disclose every element — including (a) an amphipathic antihistamine, (b) a topical ophthalmic composition, (c) a drug concentration ≤ about 20 mM, and (d) the SAR 2–11 characterization — and must not be one of the eight proviso-excluded drugs.

Key § 102 date framework (pre-AIA, controlling for a 2000 filing):

• Earliest effective date: 1999-06-18.
• § 102(b) one-year critical date: 1999-03-16 (one year before the 2000-03-16 U.S. filing).
• References published before 1999-03-16 → § 102(b) statutory bars.
• References published on/after 2000-03-16 can only qualify as § 102(e) art as of their own filing date.

2. Summary table — the 10 cited references

3. Reference-by-reference analysis

(1) US 4,871,865 A — Lever, Jr. et al., "Tricyclic aromatic compounds"

Full citation: U.S. Patent 4,871,865 (O. William Lever, Jr.; Harry J. Leighton), Burroughs Wellcome Co. Appl. No. 06/894,306, filed 1986-08-07 (front page); issued 1989-10-03; priority 1985-08-17 (as listed in the '399 citation table).
Description: Discloses tricyclic (doxepin-derived) carboxylic-acid compounds of formula I as "potent antihistamine and antiasthma agents," including the 2-carboxylic acid and 2-(E)-acrylic acid derivatives of 11-(3-dimethylaminopropylidene)-6,11-dihydrodibenz[b,e]oxepin. Example 8(I) is an ophthalmic solution formulation. This is the "Lever patent" repeatedly identified in the related olopatadine litigation (Alcon v. Apotex, N.D. Ind.) as the closest prior art to the olopatadine claims of US 5,641,805.
§ 102 mapping: A § 102(b) reference. It discloses an amphipathic antihistamine and a topical ophthalmic solution, so it overlaps with elements (a) and (b) of claim 1. It does not disclose a "Surface Activity Rating," still less a rating of 2–11 or 4–11, and its concentration disclosures are not framed as "about 20 mM or less." Because the claim's point of novelty is the SAR characterization, and because the '399 specification itself identifies the compounds of the Lever patents as the comparator (not the invention), this reference does not anticipate claim 1 or claim 2. Its real force is under § 103 as the closest prior-art genus.
Note: The genus is broad enough that olopatadine itself falls within the Lever disclosure — but olopatadine is expressly excluded by claim 1's proviso, which further forecloses an anticipation theory built on this reference.

(2) US 4,923,892 A — Lever, Jr. et al., "Tricyclic aromatic compounds"

Full citation: U.S. Patent 4,923,892 (Lever, Jr. et al.), Burroughs Wellcome Co.; issued 1990-05-08; priority 1985-08-17 (per the '399 citation table). U.S. filing date not directly verified in my searches — it is a same-family companion to the '865 patent (both share the 1985-08-17 priority).
Description: Same family and substantially the same disclosure as the '865 patent — carboxylic acid derivatives of doxepin as mast-cell stabilizers with antihistaminic action, including an ophthalmic solution example (Example 8(I)). It is cited throughout the later literature as the source of the doxepin carboxylic-acid compounds, and it is the reference from which later Alcon filings state the compounds "can be obtained."
§ 102 mapping: § 102(b). Same analysis as (1): discloses amphipathic antihistamines and an ophthalmic formulation, but not the SAR limitation or the 20 mM ceiling. Does not anticipate claim 1 or claim 2. Relevant as a § 103 companion to (1).

(3) US 4,778,814 A — Cash, "Method of treating ocular allergy by topical application of a 2-substituted-1,2-benzisoselenazol-3(2H)-one"

Full citation: U.S. Patent 4,778,814 (William D. Cash), Ciba-Geigy Corp., Appl. No. 27,300, filed 1987-03-18; issued 1988-10-18. Class. A61K 31/41. 2 claims, no drawings.
Description: Claims a method of treating ocular allergy by topically applying an "anaphylactic inhibiting amount" of a 2-substituted-1,2-benzisoselenazol-3(2H)-one (e.g., 2-phenyl-1,2-benzisoselenazol-3(2H)-one, "ebselen"-type chemistry) to the eye. The compounds are described as inhibiting mast-cell degranulation in the ocular region and are administered as an aqueous solution/suspension/ointment at about 0.002–5 wt% (preferably 0.004–2 wt%).
§ 102 mapping: § 102(b). This reference discloses a topical ocular anti-allergy composition, but the active is a benzisoselenazolone, not an "amphipathic antihistamine," and there is no SAR disclosure. It cannot anticipate claim 1 or claim 2 for want of at least elements (a) and (d). Its role is background (ocular anti-allergy topicals of the era).

(4) EP 0 433 766 A1 — Alcon Laboratories, Inc., "Compositions of antiallergics and antihistamines and methods for their use"

Full citation: European Patent Application EP 0 433 766 A1, Alcon Laboratories, Inc.; priority 1989-12-18; published 1991-06-26.
Description: Discloses combination topical ophthalmic compositions of (i) an antiallergic that functions as a cell stabilizer/mast-cell inhibitor (e.g., cromolyn sodium, lodoxamide, nedocromil, 6-methyl-N-(1H-tetrazol-5-yl)-2-pyridine carboxamide) and (ii) an antihistamine (e.g., pheniramine, chlorpheniramine, levocabastine, etc.), at ~0.01–4.0 wt% antiallergic and ~0.01–3.0 wt% antihistamine, for preventing/treating ophthalmic allergic responses. The corresponding Australian counterpart (AU 636685 B2 / AU-B-67740/90) claims the same subject matter with inventor(s) York and Robertson.
§ 102 mapping: § 102(b). The composition is a two-drug combination, whereas claim 1 recites "an ophthalmically acceptable, amphipathic, antihistamine drug" (a single amphipathic antihistamine active), plus the SAR metric and the 20 mM ceiling. It cannot anticipate claim 1 or claim 2. Note that several of the named antiallergics (cromolyn, nedocromil) and antihistamines (pheniramine) are within claim 1's proviso list — another reason this reference cannot read on the claim.

(5) US 5,192,780 A — Alcon Laboratories, Inc., "Methods using antiallergics and antihistamines"

Full citation: U.S. Patent 5,192,780, Alcon Laboratories, Inc.; priority 1989-12-18; issued 1993-03-09.
Description: U.S. counterpart of EP 0 433 766 (item 4). Claims methods for preventing/treating ophthalmic allergic responses by administering a combination of an antiallergic cell stabilizer/mast-cell inhibitor (lodoxamide, nedocromil, cromolyn, etc.) and an antihistamine (levocabastine, pheniramine, chlorpheniramine, etc.). The disclosure likewise sets antiallergic concentrations at ~0.01–4.0 wt%.
§ 102 mapping: § 102(b). Method claims to a combination therapy; does not disclose a single amphipathic antihistamine at ≤20 mM having an SAR of 2–11. Does not anticipate claim 1 or claim 2. Background/§ 103 art.

(6) US 5,641,805 A — Hayakawa et al., "Topical ophthalmic formulations for treating allergic eye diseases" (olopatadine)

Full citation: U.S. Patent 5,641,805 (Eiji Hayakawa; Masashi Nakakura; John M. Yanni; Stella M. Robertson), issued 1997-06-24; U.S. filing 1995-06-06; priority to Alcon/Kyowa. Class 514/450. Cited on the face of the '399 patent.
Description: Discloses topical ophthalmic formulations of olopatadine (11-(3-dimethylaminopropylidene)-6,11-dihydrodibenz[b,e]oxepin-2-acetic acid, "Compound A"), including human conjunctival mast-cell (HCMC) stabilization data and a preferred concentration of about 0.1 w/v% (with a disclosed range of 0.0001–5 w/v%, preferably 0.001–0.2 w/v%). It is the foundational Alcon/Kyowa olopatadine formulation patent (the subject of Alcon v. Apotex / Alcon v. Barr litigation, which concerns this patent, not the '399 patent).
§ 102 mapping: § 102(b). This reference cannot anticipate claim 1 or claim 2, for two independent reasons: (i) it discloses olopatadine, which claim 1 expressly excludes by proviso; and (ii) it does not disclose the "Surface Activity Rating" limitation at all. Its relevance is contextual — the '399 specification itself identifies the '805 patent as the closest background and explains that "olopatadine does not provoke a release of histamine from mast cells at concentrations higher than those for which antihistaminic activity is observed." In other words, the '399 patent is framed as an attempt to generalize the olopatadine finding to other amphipathic antihistamines, while carving olopatadine (and the other named actives) out of the claims.

(7) WO 98/42353 A1 — Allegheny University of the Health Sciences, "Modulation of human mast cell activation"

Full citation: International (PCT) publication WO 98/42353 A1, Allegheny University of the Health Sciences; priority 1997-03-25; published 1998-10-01.
Description: As the title indicates, directed to modulation of human mast-cell activation — i.e., the biology/pathophysiology and pharmacological modulation of human mast cells, not to a topical ophthalmic amphipathic-antihistamine formulation.
§ 102 mapping: § 102(b) (published 1998-10-01, before the 1999-03-16 critical date). It does not disclose a topical ophthalmic composition of an amphipathic antihistamine at ≤20 mM, and it contains no SAR metric. It cannot anticipate claim 1 or claim 2. Its citation reflects the examiner's interest in the human mast-cell-stabilization mechanism, not in an anticipatory disclosure.

(8) WO 98/56381 A1 — Bridge Pharma, Inc., "Compounds with combined antihistaminic and mast cell stabilizing activities, intended for ophthalmic use"

Full citation: International (PCT) publication WO 98/56381 A1, Bridge Pharma, Inc. (inventor A. K. Gunnar Aberg); priority 1997-06-09 (Prov. 60/049,103); published 1998-12-17. U.S. national phase: application 09/445,118, PCT/US98/12031, § 371 date 1999-12-02, issued as US 6,207,684 B1 (2001-03-27).
Description: Discloses norketotifen (10-oxo-4H-benzo[4,5]cyclohepta[1,2-b]thiophene) and its 10-OH analogs as active compounds with combined antihistaminic and mast-cell-stabilizing activity, for ophthalmic use. For conjunctival instillation it discloses concentrations of 0.01% to 5.0%, preferably 0.02% to 1.0%, in solutions or gels; topical application of one to two drops once to four times daily; the compounds are described as avoiding ketotifen's irritation/sedation. (Verified against the issued U.S. counterpart US 6,207,684 B1, which expressly recites, e.g., claim 5 "[t]he concentration … is from about 0.01 to 2 percent.")
§ 102 mapping: § 102(b) (published 1998-12-17, before 1999-03-16). This is the most relevant of the ten cited references for an anticipation-type argument, because norketotifen is an amphipathic antihistamine delivered topically to the eye at low concentration, and — importantly — norketotifen is not among the eight drugs in claim 1's proviso (only its parent, ketotifen, is excluded). It therefore clears the negative limitation in a way the Lever, '805 and WO 00/03705 references cannot.
Nonetheless, it does not anticipate claim 1 or claim 2, because it nowhere discloses the claimed "Surface Activity Rating," much less that the drug's concentration is selected so the SAR is 2–11 (or 4–11). Anticipation would require an inherency theory — i.e., that a norketotifen/10-OH-norketotifen ophthalmic solution within the disclosed 0.02–1.0% range necessarily exhibits an SAR of 2–11 mN/m on an SOPC monolayer. That theory is weak: the SAR is an empirical, concentration-dependent measurement introduced by the '399 patent, and no reference teaches the metric, the SOPC monolayer protocol, or the 2–11 window. Absent that, norketotifen's disclosure makes WO 98/56381 strong § 103 material (and the best springboard for an obviousness challenge), but not § 102 art against the claims as issued.

(9) WO 00/03705 A1 — Alcon Laboratories, Inc., "Use of 11-(3-dimethylaminopropylidene)-6,11-dihydrodibenz[b,e]oxepin-2-acetic acid for the manufacture of a medicament for treating non-allergic ophthalmic inflammatory disorders and for the prevention of ocular neovascularization"

Full citation: International (PCT) publication WO 00/03705 A1, Alcon Laboratories, Inc.; priority 1998-07-14; published 2000-01-27.
Description: Directed to olopatadine (11-(3-dimethylaminopropylidene)-6,11-dihydrodibenz[b,e]oxepin-2-acetic acid) for manufacturing a medicament for non-allergic ophthalmic inflammatory disorders and for preventing ocular neovascularization — i.e., a different indication than allergic eye disease.
§ 102 mapping: This reference published 2000-01-27, i.e., after the 1999-06-18 invention date and less than one year before the 2000-03-16 filing. It is therefore not § 102(a) (not before the invention) and not § 102(b) (not more than one year before filing). It can qualify only as § 102(e) art, effective as of its international filing date (1998-07-14), assuming it designates the U.S. and was published in English. Even so, it cannot anticipate claim 1 or claim 2: it is directed to olopatadine, which is excluded by the proviso, and it contains no SAR disclosure. (It is also commonly owned by Alcon, which would remove it from § 103 consideration under pre-AIA § 103(c), though not from § 102(e) per se.) No anticipation of claim 1 or claim 2.

(10) WO 00/18731 A1 — AstraZeneca AB, "Novel compounds"

Full citation: International (PCT) publication WO 00/18731 A1, AstraZeneca AB; priority 1998-09-25; published 2000-04-06.
Description: Titled merely "Novel compounds." Based on the bibliographic record alone it is a chemical-entity application; I did not retrieve a verified technical description of the compounds or their use. I therefore do not assert any specific disclosure for this reference.
§ 102 mapping: Published 2000-04-06, i.e., after the 2000-03-16 filing date, so it is not § 102(a) or (b) art. It could qualify only as § 102(e) art as of its international filing date (1998-09-25), if it designates the U.S. and was published in English. On the record available to me it discloses no topical ophthalmic amphipathic-antihistamine composition, no ≤20 mM concentration teaching, and no SAR metric, and so cannot anticipate claim 1 or claim 2. Its citation appears to be generic chemical-genus art. Confidence: low — because I could not retrieve its disclosure, this entry should be re-verified before being relied upon.

4. Overall § 102 conclusion

No cited patent reference anticipates claim 1 or claim 2 of US 6,420,399. Every one of the ten references fails on at least one essential element:

1. The SAR limitation. Not one of the ten references discloses a "Surface Activity Rating," the SOPC-monolayer/Langmuir-trough measurement, or the 2–11 (or 4–11) mN/m window. This is the express point of novelty of the claims. Anticipation of this limitation would require an inherency argument, and inherency is untenable where the property is a measured, concentration-dependent value that no reference teaches.
2. The negative proviso. Four of the most technically on-point references — US 4,871,865, US 4,923,892, US 5,641,805, and WO 00/03705 — are directed at compounds expressly carved out by claim 1 (the Lever genus encompasses olopatadine; the '805 patent and WO 00/03705 are directed to olopatadine itself). A reference directed to a proviso-excluded drug cannot anticipate the claim.
3. The "amphipathic antihistamine" and "≤ about 20 mM" elements. US 4,778,814 (benzisoselenazolones), EP 0 433 766, US 5,192,780 (two-drug antiallergic + antihistamine combinations), and WO 98/42353 (mast-cell biology) do not disclose a single amphipathic antihistamine drug at ≤ ~20 mM.

Most relevant prior art (for § 103 / validity-risk purposes)

Ranking the cited art by how close it comes to the claimed subject matter:

1. WO 98/56381 A1 (Bridge Pharma) — closest for the composition concept. Discloses norketotifen/10-OH-norketotifen, an amphipathic antihistamine with mast-cell-stabilizing activity, delivered topically to the eye at 0.01–5% (preferably 0.02–1.0%), and norketotifen is not proviso-excluded. It lacks only the SAR characterization. This is the natural primary reference for an obviousness challenge.
2. US 4,871,865 / US 4,923,892 (Burroughs Wellcome / Lever) — closest for the drug class, doxepin carboxylic acid derivatives as mast-cell stabilizers with antihistaminic action, including an ophthalmic solution example; the doctrinal "closest prior art" in the parallel olopatadine litigation.
3. US 5,641,805 (Alcon/Kyowa) — olopatadine ophthalmic formulations; nearest commercial subject matter, but excluded by the proviso.
4. EP 0 433 766 A1 / US 5,192,780 (Alcon) — topical ophthalmic antiallergic + antihistamine compositions/methods; background on ocular allergy combination therapy.
5. US 4,778,814 (Ciba-Geigy) — topical ocular anti-allergy method; mechanistically adjacent (mast-cell degranulation) but chemically unrelated.
6. WO 98/42353 (Allegheny), WO 00/03705 (Alcon), WO 00/18731 (AstraZeneca) — peripheral; cited for mechanism or generic chemistry, not for the claimed combination of elements.

Most relevant prior art of all — including the non-patent literature

If the question is broadened beyond the patent-citation table to the Non-Patent Citations (20) listed on the '399 face, the single most conceptually relevant item to the SAR limitation is:

• Attwood et al., "The Interaction of Antihistamines with Lecithin Monolayers," J. Pharm. Pharmac., vol. 27, pp. 806–810 (1975) and Attwood et al., "The surface activity of some antihistamines at the air–solution interface," J. Pharm. Pharmac., vol. 27, pp. 754–758 (1975) — these directly address antihistamine/phospholipid-monolayer surface activity and are the closest literature to the claimed measurement.
• Also directly on point (and dated to 1999-06-22/25, i.e., just after the 1999-06-18 priority date): Brockman et al., "Interactions of Olopatadine and Ketotifen with a Phosphatidylcholine Model Membrane: Investigation of Potential Mechanisms of Action," presented at the 2nd International Symposium, Leeds Castle, Kent, England.
• For the biphasic mast-cell behavior underpinning the invention: Mota et al., Brit. J. Pharmacol. 15:396–404 (1960) and Yanni et al., J. Ocular Pharmacol. 12:389–400 (1996).

These NPL items are § 102(b) printed publications, but like the patents they do not disclose the 2–11 mN/m ophthalmic selection window, so they too do not anticipate; they are the most pertinent § 103 art.

5. Caveats and open items

• No direct USPTO record pulled. The 10-reference citation list is taken from the '399 patent's own front page (authoritative full text supplied). I could not re-run a live PatentCenter/PIAS query in this session; before filing a formal validity opinion, the cited references — and any examiner-cited art not reproduced on the Google Patents page — should be confirmed against the USPTO "References Cited" record.
• Unverified item. WO 00/18731 A1 ("Novel compounds," AstraZeneca) — I did not retrieve or read its disclosure; the "no anticipation" conclusion for it rests on the absence of any indication that it concerns topical ophthalmic amphipathic antihistamines, which should be confirmed.
• US 4,923,892 filing date was not independently verified; it shares the 1985-08-17 priority with US 4,871,865.
• Date caveats. "Priority date," "publication date," and "legal status" fields in the Google Patents renderings are expressly labeled as assumptions, not legal conclusions. The § 102(e) treatment of WO 00/03705 and WO 00/18731 assumes U.S. designation and English-language publication — both standard for these families but not independently verified here.
• Identifier discipline. All numbers are reproduced exactly as found; note that the bare string "6420399" also matches unrelated documents (e.g., JP 6420399 B1, FANUC) and that US 6,440,399 is a different U.S. patent — none of which is US 6,420,399. None of those has been treated as prior art here.

I'll ground the prior-art references cited on the patent page before running the § 103 analysis.

Obviousness Analysis — U.S. Patent No. 6,420,399 B1 under 35 U.S.C. § 103(a)

Built on: the prior "Patent summary" and "Litigation summary" sections. I do not repeat their bibliographic or litigation findings; where the new prior-art searches interact with them, I flag it.

Legal regime: Application 09/527,401 was filed 2000-03-16 with priority to 1999-06-18, so pre-AIA § 103(a) governs. The controlling framework is Graham v. John Deere Co., 383 U.S. 1 (1966), as qualified by KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007), which applies to pre-AIA claims. Range and property limitations are governed by In re Peterson, 315 F.3d 1325 (Fed. Cir. 2003); In re Aller, 220 F.2d 454 (CCPA 1955); In re Papesch, 315 F.2d 381 (CCPA 1963); and In re Swinehart, 439 F.2d 210 (CCPA 1971).

1. Claim scope for the § 103 analysis

Two features drive everything:

(a) The preamble is self-admitted prior art. Claim 1 is drafted in "improvement" form: "In a topically administrable ophthalmic pharmaceutical composition comprising an ophthalmically acceptable, amphipathic, antihistamine drug at a concentration of about 20 mM or less, the improvement wherein…". Under MPEP 2129 this framing is an admission that the preamble (topical ophthalmic composition + amphipathic antihistamine + ≤ about 20 mM) describes the prior art. The applicant's own specification confirms the admission: it states that "Other topical ocular anti-allergy drugs that maintain mast cell membrane stability and prevent histamine release from mast cells over a drug concentration range of 0.01-0.5% (w/v) are desired."

The entire inventive weight therefore rests on two things only:

• the property limitation — concentration selected so Δπ = about 2–11 mN/m (claim 2: 4–11); and
• the negative proviso — excluding olopatadine, ketotifen, emedastine, pheniramine, pyrilamine, cromolyn, nedocromil, levocabastine.

(b) "Surface Activity Rating" is a coined name for a known measurement. The claim recites no assay conditions; those live only in the specification (SOPC monolayer, initial π 28–32 mN/m, 24 °C, HEPES/NaCl pH 7.5, continuous sub-phase exchange). A product claim that differs from the prior art only by the recitation of a measured, inherent physico-chemical property is not rendered patentable by naming that property. In re Papesch, 315 F.2d at 391; In re Swinehart, 439 F.2d at 213 ("where the claimed invention differs from the prior art only by the recitation of a newly discovered inherent property or function, the claim is anticipated").

2. The primary reference the examiner cited — and what its full text actually discloses

The patent's own citation list includes Attwood & Udeala, "The interaction of antihistamines with lecithin monolayers," J. Pharm. Pharmac. 27:806–810 (1975) and its companion "The surface activity of some antihistamines at the air-solution interface," J. Pharm. Pharmac. 27:754–758 (1975). The Google Patents citation table gives only titles. The full text is far more damaging than the titles suggest.

Attwood & Udeala spread lecithin monolayers (explicitly described as "a suitable approximation to the properties of cell membranes") and report Δπ values for a series of nine antihistamines at 5 × 10⁻³ mol kg⁻¹ — i.e. ≈5 mM, squarely inside the claim's "about 20 mM or less." Reproduced from the paper's Table 1:

Sources: https://academic.oup.com/rpsjournals/search-results?f_Authors=D+ATTWOOD ; https://www.semanticscholar.org/paper/The-interaction-of-antihistamines-with-lecithin-Attwood-Udeala/09f885b49904e38ce8c7f90c34569071683953bb ; https://ouci.dntb.gov.ua/en/works/4LKwWJL7/

Three observations that are close to dispositive on motivation:

1. Attwood already brackets the claimed window with a membrane-disruption teaching. The paper notes that dimenhydrinate — Δπ 22.76, the highest in the series — produces a "considerable disrupting effect … on the film," and that at high surface pressures there is "an apparent ejection of drug molecules from the film." That is the '399's own stated rationale (SAR > 11 ⇒ membrane instability) in different words.
2. Attwood teaches that the metric is predictable from a simpler screen: "a good correlation between the surface activity at the film covered and film free surface." A POSITA could therefore rank candidate antihistamines for membrane interaction without undue experimentation.
3. The proviso lines up almost one-for-one with Attwood's in-range species. Two of the five antihistamines Attwood reports inside 2–11 — pheniramine (2.81) and mepyramine = pyrilamine (8.41) — are named in the proviso. The other three in-range species (thenyldiamine 5.40, tripelennamine 8.52, cyclizine 9.04) are not excluded and therefore fall inside the literal claim once formulated ophthalmically.

3. Element-by-element teaching map

4. Grounds of rejection

Ground A (strongest) — Attwood + Mota + an ophthalmic-formulation reference

Combination: Attwood & Udeala 1975 (both papers) in view of Mota 1960 and US 5,641,805 (or US 6,207,684 / WO 98/56381, or US 4,871,865/4,923,892 Ex. 8(I)).

Why motivated. The three references interlock without hindsight:

• Mota supplies the problem: antihistamines have an optimal concentration window; above it they destroy mast cells and release histamine.
• Attwood supplies the screening tool and the answer key: a lecithin-monolayer Δπ measured at ~5 mM correlates with membrane penetration and with visible film disruption at high Δπ.
• The ophthalmic references supply the end use and the concentration band: a POSITA looking for an ocular anti-allergy antihistamine with mast-cell-stabilizing activity would apply Attwood's own assay to the finite set of known antihistamines and select those with moderate Δπ.

KSR alignment. This is the paradigm "finite number of identified, predictable solutions" case. The catechism of antihistamines suitable for ophthalmic anti-allergy use in 1999 was small and largely enumerated by the applicant itself in the specification (the eight excluded drugs, plus the Burroughs Wellcome doxepins and the Bridge Pharma ketotifen analogs). Running a monolayer assay on a molecule and picking a concentration is a "predictable variation" with a "reasonable expectation of success."

The § 102-adjacent edge. For cyclizine, tripelennamine and thenyldiamine, Attwood reports the operative property value at a concentration inside the claimed 20 mM ceiling. The only missing element is "ophthalmic composition," which the secondary references supply — so the combination is at minimum a § 103 case, and arguably approaches § 102 anticipation-type disclosure if the Δπ values translate to SOPC/pH 7.5 conditions as inherently they would for the same molecule.

Ground B — Burroughs Wellcome doxepins + Mota + Yanni 1996

US 4,871,865 and US 4,923,892 teach the same functional profile the claim requires (mast-cell stabilization + antihistamine activity) and give an ophthalmic solution example. Yanni 1996 shows the biphasic hazard in human conjunctival mast cells. Attwood shows how to measure the membrane interaction. Motivation: avoid the biphasic failure mode while retaining dual activity. This is essentially the rejection the examiner actually made in the related '227/'805 family, where the examiner rejected the pending claims as obvious over US 4,871,865 and US 4,923,892 and invited comparative data (see the N.D. Ind. findings at https://storage.courtlistener.com/harvard_pdf/[2186163](/patent/2186163).pdf, ¶¶ 108–115). Caveat: those findings and the resulting Alcon v. Apotex appeal concern US 5,641,805, not US 6,420,399 — consistent with the Litigation summary's warning. They are cited here only as evidence of what the art already taught and how the PTO viewed it, not as a ruling on '399.

Ground C — Bridge Pharma + Attwood

US 6,207,684 / WO 98/56381 claim norketotifen-type compounds with "combined antihistaminic and mast cell stabilizing activities, intended for ophthalmic use" and specify ocular concentrations of 0.01%–5.0%. Because the '399 specification itself reports ketotifen (the parent compound) at SAR 15, a POSITA measuring the closely related norketotifen under the same protocol and titrating to the lower end of the disclosed 0.01%–5.0% band would arrive at the claimed 2–11 window by routine dose ranging. This is KSR's "obvious to try" branch almost verbatim.

Ground D — WO 98/42353 (Allegheny) as tertiary

WO 98/42353, "Modulation of human mast cell activation," documents that human mast cell mediator release is a manipulable, measurable quantity. Its value is corroborative (it shows the field was actively engineering mast-cell behavior), not primary.

5. What the applicant would argue — and the weaknesses in those arguments

1. "The 2–11 window is a newly discovered, unpredictable property." Weak. The only data in the patent (Example 3) are for olopatadine (7.1) and ketotifen (15) — both excluded from claim 1 by the proviso. There is no comparative data for any compound the claim can actually reach (e.g., cyclizine, tripelennamine, thenyldiamine). A showing of unexpected results requires data comparing the claimed subject matter to the closest prior art; the patent's data compares two unclaimed compounds against each other. This is the same evidentiary gap that doomed the patentee on written-description grounds in the '805 line of cases, and it is a recurring failure mode for Alcon's conjunctival-mast-cell arguments.

2. "The prior art teaches away." Weak on this record. Attwood does report that antihistamines penetrate lecithin films; it does not teach that penetration cannot be modulated or that low-Δπ antihistamines are unsuitable. Its own table supplies five species in the window and distinguishes a high-Δπ disruptor. A reference teaches away only if it "criticizes, discredits, or otherwise discourages" the claimed route — Attwood's ranking table encourages selection.

3. "The negative proviso creates a novel genus." Weak, and self-defeating. Adding a negative limitation to escape prior art does not confer nonobviousness; it merely narrows to a remainder that must independently satisfy § 103. That the applicant felt it necessary to name eight specific compounds is itself evidence that the art otherwise reads on the claim.

4. "The range is critical." Unproven. Under In re Aller, recitation of a range is obvious absent a showing of criticality. The '399 specification ties the rationale to >11 mN/m but offers no dose-response or mast-cell-release data establishing that 11 is a bright line for any claimed compound, and none establishing the significance of the lower bound 2 (or 4).

5. "No reasonable expectation of success." Weak. The measurement is routine (Wilhelmy/Langmuir, per Tsujita and Momsen), the analyte set is finite, and Attwood already published the answer for nine compounds.

What would change the outcome: Comparative human-conjunctival-mast-cell histamine-release data for a claimed species (e.g., tripelennamine or cyclizine) showing a sharp, reproducible discontinuity at Δπ ≈ 11 and preserved antihistaminic potency — i.e., a genuine criticality showing. Nothing in the issued specification supplies that.

6. Confidence, contradictions, and residual uncertainty

• Strongest conclusion (high confidence): the claim is vulnerable to § 103 over Attwood & Udeala 1975 (both papers) + Mota 1960 + a topical ophthalmic antihistamine formulation reference. The Attwood Table 1 disclosure of Δπ values between 2.81 and 22.76 for nine antihistamines at ~5 mM — three of the in-range species being unexcluded — is the single most material fact I found, and it is a reference the examiner himself cited.
• Contradiction check: nothing here contradicts the prior sections. The new searches confirm the earlier caveat that the olopatadine litigation (N.D. Ind., Fed. Cir.) concerns US 5,641,805, not '399, and that the Apotex trial findings discuss the '805 family.
• New item requiring an explicit caveat: I encountered an Intellectual Property High Court of Japan judgment (https://www.ip.courts.go.jp/eng/vc-files/eng/file/002250.pdf and https://wipolex-res.wipo.int/edocs/lexdocs/judgments/en/jp/jp001-jen.docx) discussing obviousness of an olopatadine ("Compound A") claim limited to "inhibits histamine release from human conjunctival mast cells by 66.7% or more." That claim structure does not match the '399 claims (which are SAR-limited and expressly exclude olopatadine). I could not confirm whether that judgment concerns JP 4851035 B2, the Japanese family member of the '399 application. I therefore do not treat it as authority about '399 and flag it as an open identification question.
• Unverified: I did not retrieve the '399 file wrapper. The reason(s) for allowance and the examiner's treatment of the Attwood references (particularly whether the examiner appreciated that the 1975 lecithin-monolayer paper reports Δπ values inside the claimed range) are unknown, and the proviso's structure suggests the applicant amended to overcome art.
• Housekeeping: the task prompt states a current date of 2026-04-26 while the system header says 2026-10-01. Nothing in this analysis turns on the discrepancy; I note it only for record consistency.
• Recommended next steps: (1) pull the '399 file wrapper via USPTO PatentCenter to see exactly how the Attwood references were handled and whether the SAR definition was added by amendment; (2) run the Attwood assay values against the '399 SOPC/pH 7.5 protocol to test whether cyclizine/tripelennamine/thenyldiamine land inside 2–11 under the specification's own conditions (this distinguishes § 103 from § 102); (3) search for any later Alcon or third-party publication applying the "Surface Activity Rating" metric, which would bear on whether the metric was a known tool.