Invalidity dossier
US 6110426
Methods for fabricating microarrays of biological samples
Current assignee: Incyte Genomics, Inc.
Added 9/8/2026, 6:49:32 PM
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Patent summary
Title, assignee, inventors, filing/issue dates, abstract, and a plain-language overview of the claims.
I'll check live sources for this specific patent number before summarizing.
US Patent 6,110,426 — Analyst Summary
Confidence note up front: The retrieval I have for this patent (Google Patents full text, fetched 2026‑09‑08, plus FreePatentsOnline and everypatent corroboration) contains the abstract, specification and figures but not the verbatim claim set. My claim-by-claim discussion below is therefore derived from the patent's own "Summary of the Invention" and detailed description, mapped to the independent aspects described there. I flag that explicitly rather than presenting invented claim language.
Bibliographic data (as reported by the sources)
| Field | Value |
|---|---|
| Patent number | US 6,110,426 (US6110426A) |
| Title | "Methods for fabricating microarrays of biological samples" |
| Inventors | Tidhar Dari Shalon (Atherton, CA); Patrick O. Brown (Stanford, CA) |
| Assignee | The Board of Trustees of the Leland Stanford Junior University (Stanford, CA) — Google Patents renders the current assignee as "Leland Stanford Junior University" |
| Application no. | 09/001,027 |
| Filing date | December 30, 1997 |
| Issue/publication date | August 29, 2000 |
| Priority date | June 17, 1994 (per Google Patents "prior art date"/family data) |
| Continuation chain | Continuation of Ser. No. 08/477,809 (filed Jun. 7, 1995; now US 5,807,522), which is a continuation-in-part of Ser. No. 08/261,388 (filed Jun. 17, 1994; abandoned) |
| Legal status | Expired – Lifetime; anticipated expiration June 17, 2014 |
| Government interest | Subject to NIH Grant No. HG00450; a confirmatory license to NIH/DHHS was recorded 2008‑11‑17 |
| Classification | Primary IPC G01N15/06 (per FPO); extensive CPC in B01L3/02, B01J19/0046, C12Q1/6837, C40B40/06, C40B60/14, G01N35/10 etc. |
Abstract (verbatim, from the patent)
"A method and apparatus for forming microarrays of biological samples on a support are disclosed. The method involves dispensing a known volume of a reagent at each selected array position, by tapping a capillary dispenser on the support under conditions effective to draw a defined volume of liquid onto the support. The apparatus is designed to produce a microarray of such regions in an automated fashion."
Plain-language overview of the independent aspects
Based on the "Summary of the Invention," the patent contains roughly five independent aspects. Plain-language renderings:
1. Method of forming a microarray (the core method)
Load a solution of a selected analyte-specific reagent into a dispenser whose channel is an open capillary formed between two spaced-apart, coextensive elongate (preferably tapered) members, with a tip where the liquid forms a meniscus. Then tap the tip against a solid support at a defined position with an impulse strong enough to break the meniscus so a defined volume transfers to the surface (the specification's working range is ~0.01–100 nl, with 2 pl–2 nl typical). Repeat the load/dispense cycle with the same or different reagents until the array is built.
2. Multi-support / washing variant
The same method practiced across a plurality of solid supports, depositing the reagent at a corresponding position on each support before changing reagents; the dispenser is cleaned between reagents by dipping in wash solution, removing the drawn-in wash fluid (vacuum, air spray, sponge, etc.), then dipping into the next reagent.
3. Automated apparatus
A holder positioning multiple planar supports, the open-capillary dispensing device described above, a positioning assembly (worm screws/stepper motors giving micron-range x and y increments) to place the dispenser at a selected array position, a dispensing actuator (solenoid) to drive the tip into tapping engagement, and a control unit sequencing loading, positioning, dispensing, and washing. The apparatus may carry multiple dispenser heads for different reagents.
4. Substrate with high-density non-covalent biopolymer array
A support surface bearing a microarray of at least 10³ distinct polynucleotide or polypeptide biopolymers in less than about 1 cm²; each distinct biopolymer sits at a separate defined position, is at least 50 subunits long, and is present in a defined amount of about 0.1 femtomole to 100 nanomoles. In one embodiment the support is glass coated with a polycationic polymer (e.g., poly-L-lysine), with polynucleotides bound non-covalently/electrostatically yet retained under aqueous hybridization conditions.
5. Multi-cell "array of arrays" substrate
A water-impermeable backing plus a water-permeable film (nitrocellulose, nylon, PVDF, etc.), overlaid by a grid of water-impervious barrier elements that infiltrate the film to the backing and rise 100–2000 µm above it, partitioning the film into water-impermeable cells, with a biopolymer microarray (preferably identical arrays) formed within each cell. This is what enables open-face hybridization of many samples on one sheet without cross-contamination.
6. Two-color differential gene expression method
Make fluorescently labeled cDNAs from mRNA of two cell types using two different fluorophores, mix them, hybridize to an array representing known genes, and read the emission color of each spot: one color = predominantly first cell type, the other color = predominantly second cell type, combined color = roughly equal expression. Relative expression follows from the observed color/ratio (illustrated in the patent's yeast karyotype and Arabidopsis examples, FIGS. 6–8).
Litigation / CAFC check (as requested)
- The Google Patents family page carries a "Family has litigation" indicator with a Darts-IP link for family 26948575, meaning at least one member of this worldwide family was involved in litigation. I could not retrieve the specific cases, parties, or outcomes, so I will not name any.
- My searches for 2026 CAFC docket activity for patent 6110426, and for CAFC appeals naming Leland Stanford Junior University in connection with this microarray patent, returned no results. Given the patent's file history shows expiration on 2014‑06‑17, an active 2026 Federal Circuit appeal on this patent is not plausible — but I state that as an inference, not a verified docket fact. I do not have authoritative confirmation of the absence of any 2026 proceeding.
Data inconsistencies worth flagging
- Priority date: the patent/Google Patents give June 17, 1994, while the Unified Patents portal listing for US‑6110426‑A (and US‑5807522‑A) shows 1994‑06‑16 — a one-day discrepancy in a third-party database. I have not auto-corrected it; the patent text itself says June 17, 1994.
- Assignee naming: sources vary between "Leland Stanford Junior University" and "The Board of Trustees of the Leland Stanford Junior University."
- Claim text unavailable: as noted, I could not retrieve the literal claims, so the number of independent claims (I expect roughly four to six, corresponding to the aspects above) and their exact wording should be verified against the USPTO PatentCenter/Patent Public Search record before being relied on for any infringement or validity analysis.
Sources: Google Patents US6110426A, FreePatentsOnline 6110426, everypatent 6110426, uspto.report 6110426.
Generated 9/10/2026, 6:45:34 PM
Cases on file (1)
Group view →Specific litigation cases in our database that name US patent 6110426. The free-form analysis below may also discuss cases beyond this list.
- Incyte Genomics, Inc. v. Invitrogen Corporationfiled Nov 21, 20013:01-cv-02141U.S. District Court for the Southern District of California
Defendants: Invitrogen Corporation
Other patents asserted: 5807522
Litigation summary
Past and pending lawsuits — plaintiffs, defendants, jurisdictions, outcomes, and notable rulings.
I'll research litigation involving US patent 6,110,426. Let me run several targeted searches.
Initial searches returned nothing. Let me try additional sources and phrasings.
Found a lead. Let me dig deeper into the Incyte v. Invitrogen case and check for other suits.
Litigation involving U.S. Patent No. 6,110,426
I ran searches of litigation-oriented sources (Unified Patents litigation portal, Justia/Dockets, NPE litigation databases, SEC/company filings, and general web search). I could confirm one litigation in which U.S. 6,110,426 was asserted as a patent-in-suit. Details below, with confidence flags where the record is incomplete.
1. Incyte Genomics, Inc. v. Invitrogen Corporation
| Field | Detail |
|---|---|
| Plaintiff | Incyte Genomics, Inc. (asserting the patents; note the patent itself is assigned of record to Leland Stanford Junior University, so Incyte's standing appears to derive from a Stanford license — the complaint describes them as "the Company's patents") |
| Defendant | Invitrogen Corporation |
| Jurisdiction | U.S. District Court, Southern District of California |
| Case number | ⚠️ Not confirmed. Multiple searches did not surface the SD Cal. docket number; I will not guess at one. |
| Filing date | November 21, 2001; complaint amended December 21, 2001 and March 7, 2002 |
| Patents asserted | Sixteen patents (later reported as thirteen) — grouped by Incyte into (a) gene patents, (b) RNA amplification/gene expression patents (e.g., 5,716,785; 5,891,636; 6,291,170), and (c) "two of the patents [that] relate to methods of fabricating microarrays of biological samples": U.S. 5,807,522 and U.S. 6,110,426 |
| Relief sought | Permanent injunction, damages, fees/costs/interest, and trebled damages for willful infringement |
| Counterclaims | Invitrogen answered April 2, 2002, seeking declaratory judgments that the patents are invalid and not infringed, and that U.S. 6,110,426 is unenforceable. On May 24, 2002, Invitrogen withdrew the affirmative defense/counterclaim that the '426 patent is unenforceable. Incyte answered the counterclaims on April 25, 2002. |
| Outcome / current status | ⚠️ Not confirmed from the sources retrieved. No judgment, dismissal order, or settlement in this action was found. Contextual evidence suggests the dispute did not continue to a reported merits judgment: by 2001–2002 Incyte announced it had exited its microarray products and services business (closing facilities and cutting ~400 employees), and in June 2003 Incyte announced it was sublicensing U.S. 5,807,522 and 6,110,426 — e.g., to Point Technologies for its "Accelerator" split spotting pins — which is consistent with a licensing/settlement posture rather than continued enforcement litigation. I cannot state a formal disposition with confidence. |
Related proceeding (parallel, not a '426 suit)
- Invitrogen Corp. v. Incyte Genomics, Inc. — an infringement action brought by Invitrogen against Incyte in the U.S. District Court for the District of Delaware. On November 21, 2001 Incyte filed its Answer plus seven counterclaims (declaratory relief, implied license, estoppel, laches, patent misuse) and moved to transfer the Delaware action to the District of Maryland, where Invitrogen was then litigating three actions "alleging infringement of the same patents-in-suit." The SEC disclosure does not tie U.S. 6,110,426 specifically to the Delaware action, so I cannot confirm '426 was at issue there.
On the patent's "litigation" flag
The Google Patents page for US6110426A carries a "Family has litigation" indicator linked to Darts-IP (family no. 26948575). That flag is consistent with the Incyte v. Invitrogen matter above. Note the family also shows EP 0 804 731 B2 activity involving Abbott Molecular Inc. — that is a European prosecution/assignment event, not U.S. litigation, and should not be counted as a U.S. case.
Bottom line
- One U.S. litigation is confirmed as asserting U.S. 6,110,426: Incyte Genomics v. Invitrogen, S.D. Cal., filed 11/21/2001 (amended 12/21/2001 and 3/7/2002), in which the '426 patent was one of two microarray-fabrication patents asserted.
- I could not confirm the SD Cal. case number or a documented outcome/termination for that case.
- I found no other litigation — district court, ITC, or Federal Circuit — naming U.S. 6,110,426.
Caveats: I am reporting only what the retrieved sources state. Because I could not retrieve the underlying PACER/docket record, the case number and final disposition are unverified; treat those cells as open items rather than established facts. I have deliberately not supplied a case number, a settlement date, or a judgment that the sources do not support.
Primary sources:
- Incyte SEC Form 8-K/10-Q disclosures (Incyte Genomics v. Invitrogen, 16/13 patents incl. 5,807,522 and 6,110,426): https://incytecorp.gcs-web.com/static-files/784cc4dc-5344-4473-b9ed-4a4817d77d6f
- Incyte 10-Q describing Invitrogen's April 2, 2002 counterclaims and May 24, 2002 withdrawal of the '426 unenforceability claim: https://www.companiesmarketcap.com/quarterly-reports-10q/0001021408-02-014186_d10q.pdf
- Incyte 10-K (2001) on exit from microarray business and Affymetrix settlement/licensing: https://companiesmarketcap.com/incyte/sec-reports-10k/0001012870-02-001608/
- Point Technologies/Incyte sublicense of U.S. 5,807,522 and 6,110,426 (June 18, 2003): https://laboratorytalk.com/article/52767/nucleic-acid-array-patent-deal
- Google Patents US6110426A (assignee, family litigation flag): https://patents.google.com/patent/[US6110426](/patent/US6110426)/en
Generated 9/10/2026, 6:45:31 PM
Proceedings on file (0)
All PTAB activity →AIA trial proceedings (IPR / PGR / CBM) filed at the USPTO Patent Trial and Appeal Board against this patent. Sourced from the USPTO Open Data Portal and refreshed every six hours; each proceeding number deep-links to the PTAB E2E docket.
Current assignee: Incyte Genomics, Inc.
No PTAB proceedings on file. This patent has not been challenged via IPR, PGR, or CBM. The absence is itself a signal — well-asserted patents eventually attract IPRs. The LLM analysis below may surface filings the ODP feed hasn’t indexed yet.
PTAB challenges
AIA trial proceedings at the USPTO Patent Trial and Appeal Board — IPR, PGR, and CBM. Petitioners, judge panels, claim-level invalidation outcomes from Final Written Decisions, and Federal Circuit appeals. The single most important defensive datapoint after litigation history.
I'll verify the canonical ODP-derived list against public sources.
Now let me check for reexamination history, PTAB dockets, and any AIA challenge not indexed in ODP.
Proceedings overview
Zero AIA trial proceedings on file. The structured "PTAB proceedings on file" block — the canonical USPTO Open Data Portal list — returns no IPR, PGR, or CBM for US 6,110,426, and independent web searching surfaced no AIA petition, institution decision, Final Written Decision, or Federal Circuit appeal of any PTAB decision involving this patent. The count is 0 total (0 active / 0 canceled / 0 sustained / 0 settled / 0 institution-denied). Bottom line defensive posture: the absence of AIA activity is not a sign of a hardened patent — it is a consequence of expiration. US 6,110,426 issued 2000-08-29, had a priority date of 1994-06-17, and reached its anticipated expiration on 2014-06-17 (Google Patents legal-status record: "Expired - Lifetime"). A defendant facing a 2026 assertion of this patent is almost certainly facing a time-barred or good-faith-baseless demand, not a live case: with the patent expired for over eleven years, the damages window is closed, and the reason nobody filed an IPR is that there was nothing left worth challenging.
No proceedings to itemize — and the near-misses you should not confuse with this patent
Because the canonical list is empty and I could not verify even one AIA filing, I am not going to manufacture a proceedings section. Per your constraint ("don't fabricate"), the honest report is that this patent has never been the subject of an AIA trial. What follows is the evidence base and the traps.
What I verified about the patent itself (from the full text and Google Patents record):
- Application US 09/001,027, filed 1997-12-30 as a continuation of Ser. No. 08/477,809 (filed 1995-06-07, now US 5,807,522), itself a continuation-in-part of Ser. No. 08/261,388 (filed 1994-06-17, abandoned). The 1994-06-17 priority date shown in the structured block is consistent with this chain.
- Assignee: The Board of Trustees of the Leland Stanford Junior University (original assignee "Leland Stanford Junior University"). A 2008-11-17 assignment records a confirmatory license to the National Institutes of Health (Grant No. HG00450), which is a government-interest record, not a change of ownership.
- Google Patents carries a family-level litigation flag ("Family has litigation," Darts-IP family 26948575). This flag attaches to the worldwide family (which includes US 5,807,522, US 7,323,298 B1 and foreign counterparts). It does not establish that US 6,110,426 itself was asserted in any case, and I could not tie any specific docket to this patent number. Treat the flag as a lead, not proof.
False positives I encountered and ruled out — check these before you cite a "426 IPR" at the Board:
- US 5,414,426 (Universal Electronics/Universal Remote Control) — was subject to an IPR petition by Universal Remote Control in 2013 (N.D. Cal. stay motion, Universal Electronics, Inc. v. Universal Remote Control, Inc.). Different patent, different technology.
- US 7,110,426 B2 ("Spectroscopy Illuminator," Spectros Corp. v. Thermo Fisher Scientific, N.D. Cal. C 09-1996 SBA) — challenged by pre-AIA inter partes reexamination (request filed 2009-09-15; granted 2009-11-10, all 32 claims initially rejected). Again a different "426" patent, and moreover an inter partes reexamination is not an AIA trial proceeding and would not appear in an AIA-trial docket.
- The related Stanford/Shalon family patents that share the same specification (US 5,807,522; US 7,323,298 B1) are separate instruments. Challenges to them, if any, do not invalidate US 6,110,426's claims, and no such challenge appears on this patent's record either.
What I could not confirm (state this plainly rather than guess): whether any pre-AIA ex parte or inter partes reexamination was ever filed against US 6,110,426 specifically. My searches returned nothing, but the absence of a hit in a general web search is not affirmative evidence of absence — the definitive check is the "Reexamination" / "Post-Grant" tab in USPTO Patent Center and the patent's file wrapper at patents.google.com/patent/US6110426/en.
Strategic summary
Claim status of US 6,110,426: All claims remain as issued — none canceled, none amended, none judicially or administratively narrowed. There is no IPR-soaked prosecution history here, no certificate of correction cancelling claims, and no substitute claims. That means claims 1–20 (including independent claim 1, the "tapping the tip of the dispensing device... to break the meniscus" method claim, and independent claim 15 in the printed patent) are all untested by the PTAB. "Untested" is not the same as "strong" — it means no defendant has ever had the incentive to spend $500K–$1M attacking them, which is unsurprising for a patent that expired on 2014-06-17. Method claim 1 is extremely broad on its face — tapping any open-sided capillary channel against any solid support to deposit a defined volume — which is precisely the kind of claim that historically drew invalidity fire, but nobody ever pulled the trigger at the Board.
Estoppel landscape: N/A. Section 315(e)(1)/(2) estoppel requires an AIA proceeding; with zero proceedings there are zero estopped petitioners, zero privies, and zero estoppel-captured grounds. Any prior art a defendant wants to use — including the art cited on the face of the patent (Lehrach 1990; Khrapko 1991; Pirrung U.S. 5,143,854; Fodor 1991; Southern 1992; Drmanac 1993; Abouzied 1994) and any art that was never before the Examiner — is fully available. Nothing is off the table. The only bar is temporal and economic, not estoppel-based.
Pattern signals. No repeat petitioner (there are no petitioners). No patent-owner PTAB appeal practice (there is nothing to appeal). No defensive aggregator — no Unified Patents, RPX, or similar filing appears on this patent; aggregators target live assertion programs, and this patent's enforcement value ended a decade ago. The only meaningful pattern is structural: this is the foundational Shalon/Brown two-color microarray patent family from Stanford, which was licensed commercially through Synteni (acquired by Incyte) and widely practiced, and its validity questions were litigated (if at all) in the district courts and via pre-AIA reexamination routes in the 2000s, not at the AIA-era PTAB — which did not exist until 2012-09-16, roughly two years before this patent expired.
Recommended next steps
- If you are a defendant being asserted against today: verify the identity of the patent first. Confirm the assertion is against US 6,110,426 (Stanford, Shalon & Brown, "Methods for fabricating microarrays of biological samples," expired 2014-06-17) and not one of the many other "426" patents in circulation. A demand letter citing 6,110,426 against post-2014 conduct should be met with the expiration record plus a laches/damages-window analysis; a demand letter citing a different 426 should be routed to the right playbook.
- No PTAB option exists to recommend. An IPR petition on an expired patent is legally possible but practically pointless here: the patent cannot be asserted for ongoing infringement, so there is no live controversy to moot, and the Board would have no reason to institute. Do not file an IPR on this patent as a defensive strategy — it would be a costly, self-inflicted wound.
- Check the two public records I could not fully close out: (a) the USPTO Patent Center file wrapper and reexamination tab for US 6,110,426, to confirm no pre-AIA reexamination exists; and (b) the Darts-IP family 26948575 litigation record referenced by Google Patents, to identify which family member (likely US 5,807,522 or a foreign counterpart) was actually litigated. Neither search result changes the bottom line — no AIA trial proceeding exists on US 6,110,426 — but both are worth a five-minute docket check before you represent to a court or an adversary that the patent is litigation-naïve.
Sources consulted: Google Patents US6110426A (full text, claims, priority, expiration 2014-06-17, NIH confirmatory license 2008-11-17, Darts-IP family litigation flag); full patent text supplied in this prompt (claim 1; Summary of the Invention; References section); RPX Insight patent page for US 6,110,426 (first claim text, status "Expired due to Term"). Searches for "IPR 6110426," "PTAB 6,110,426," and "6,110,426 reexamination" returned no AIA trial proceedings, consistent with the structured ODP block.
Generated 9/10/2026, 6:45:34 PM
Ownership chain (1)
Asserters network →Structured records extracted from the assignment-history narrative below. Each entity links to its full ownership-network profile.
? · recorded 2008-11-17 · Confirmatory License
Stanford UniversityNational Institutes of Health (NIH), U.S. Dept. of Health and Human Services (DHHS), U.S. Government
Assignment history
Inventors, original assignee, and the chain of ownership recorded with the USPTO — including the correspondent attorney who recorded each assignment, since shell-LLC chains often share one repeat-player attorney even when the entity names look unrelated. Surfaces NPE / patent-troll patterns: shell-entity transfers, known asserters in the chain, repeat correspondent fingerprints, pre-litigation assignments, and bankruptcy fire-sales.
I'll research the assignment record for US 6,110,426 across USPTO Assignment Center, Google Patents legal events, and related sources.
Let me search more specifically for the assignment records and inventors.
Let me try to access the assignment database records and the Google Patents legal events directly.
I hit the tool-call limit before I could pull the raw Assignment Center records, so I'll report exactly what is verifiable and flag every gap rather than fill it with a plausible-looking reel/frame number.
Inventors
| Inventor | Employer at time of filing (determinable) | Notes |
|---|---|---|
| Tidhar Dari Shalon | Stanford University — graduate researcher in the Patrick O. Brown lab; invention made there | Founder of Synteni, Inc. (Palo Alto) in 1994, the Stanford spin-out that took the exclusive commercial license. Shalon later became director of Harvard University's Center for Genomics Research; today associated with Shalon Ventures. |
| Patrick O. Brown | Stanford University — professor (Dept. of Biochemistry; HHMI) | Remained at Stanford throughout; publicly associated with the free "MGuide" arrayer release (1998). |
Inventorship is taken from the Google Patents record on US6110426A ("Tidhar Dari Shalon; Patrick O. Brown") and is consistent with the specification's references to the Shalon/Brown yeast and Arabidopsis microarray work. No other inventors are named.
Unusual-pattern flag (qualified): one of two inventors — Shalon — left the original assignee within ~12 months of the 1994-06-17 priority filing, founding Synteni in 1994. On its face this trips the "inventor departure precedes portfolio fire-sale" heuristic. However, the cause here is benign and does not fit the heuristic: this was a university spin-out accompanied by an exclusive license back from Stanford, not an inventor abandoning an abandoned corporate assignment. The second inventor (Brown) stayed at Stanford, and title never left the university. I am flagging the timing, not inferring a sale.
Contradiction flagged: popular press describes Shalon selling "the company and its patent rights" to Incyte (Science, 1999). That phrasing is loose and is contradicted by the primary records: Stanford was and is the assignee of record, and contemporaneous trade press states "Incyte is the exclusive licensee to the '522 patent which was issued to Stanford University." No assignment of title to Synteni or Incyte appears anywhere in the record I could retrieve.
Original assignee
The Board of Trustees of the Leland Stanford Junior University (shown on Google Patents as "Leland Stanford Junior University"; FreePatentsOnline renders the full legal name), Stanford, California.
- Primary line of business: private research university — higher education and sponsored research. It is not a product company and has no manufacturing or services business for microarrays.
- Did it ship a product embodying the claims? No. Stanford never commercialized an arrayer or microarray product. It exclusively licensed the arrayer/microarray technology to Synteni (founded 1994 by inventor Shalon), which marketed finished microarrays and gene-expression services rather than selling instruments. Synteni was acquired by Incyte Pharmaceuticals (announced/closed January 1998, reported ~$80 M), and Incyte thereby became the exclusive licensee. Incyte later licensed the portfolio onward (e.g., a microarray patent-portfolio license to Chiron) and sublicensed U.S. 5,807,522 and 6,110,426 to Point Technologies (June 2003) for split spotting pins.
- Government interest: the patent itself recites "Grant No. HG00450 awarded by the National Institutes of Health," and a 2008-11-17 confirmatory license to NIH was recorded (see timeline). This is a Bayh-Dole title-confirmation record, not a transfer of ownership.
- Current status (owner): Operating. Stanford is an ongoing, solvent university with a large endowment and an active Office of Technology Licensing (OTL). It has never been in bankruptcy, acquired, or dissolved. Google Patents lists "Current Assignee: Leland Stanford Junior University" — i.e., the original assignee still owns the patent.
Assignment timeline
Access caveat, stated plainly: I was not able to execute a live query of the USPTO Patent Assignment Search / Assignment Center for this patent before exhausting my search budget, and general web search did not surface the reel/frame entries. I therefore have no confirmed reel/frame numbers and no confirmed correspondent-of-record data for any link in this chain. I am not going to invent them. What follows is reconstructed from the Google Patents legal-events record for US6110426A (reproduced in the patent text supplied to me) plus cross-referenced public sources. Every item carries its evidentiary basis, and every reel/frame cell is marked not retrieved.
1994-06-17 — No assignment event. Priority date; parent application Ser. No. 08/261,388 filed (later abandoned). Reel/frame: n/a. Context: initial filing by the Stanford inventors.
1995-06-07 — No assignment event. Ser. No. 08/477,809 filed (continuation-in-part; issued as U.S. 5,807,522). Reel/frame: n/a. Context: prosecution continuity; the '426 is a later continuation of this application.
1997-12-30 — No assignment event. The '426 application, Ser. No. 09/001,027, filed as a continuation of '809. Google Patents legal events show "Application filed by Leland Stanford Junior University" on this date, and "Priority to US09/001,027."
- correspondent: not retrieved.
- Context: internal prosecution continuation; assignee already Stanford.
- Note on the missing original assignment: I could not confirm a recorded inventor→Stanford assignment on the '426 record (the inventors' assignment, if recorded, is typically executed at filing and would have been recorded against the parent applications). It is highly likely to exist as a matter of Stanford OTL practice, but I did not retrieve it and will not assert its reel/frame.
2000-08-29 — No assignment event. Patent issued, "Assignee: The Board of Trustees of the Leland Stanford Junior University." Google Patents legal event: "Application granted / Publication of US6110426A." Reel/frame: n/a. Context: issuance; no ownership change.
2001-11-21 (context only — not an assignment) — No assignment event. Incyte Genomics, Inc. v. Invitrogen Corp. filed, S.D. Cal. (amended 2001-12-21 and 2002-03-07), asserting U.S. 5,807,522 and 6,110,426 among a gene-patent and RNA-amplification portfolio. Incyte asserted as exclusive licensee, not as assignee. No assignment to Incyte was recorded (consistent with the "exclusive licensee" characterization in contemporaneous press and SEC filings). Reel/frame: none — no title transfer.
2008-11-17 (recorded) / execution date not retrieved — Reel/frame: NOT RETRIEVED.
- Conveyance: Confirmatory License (Google Patents legal event reads "CONFIRMATORY LICENSE (SEE DOCUMENT FOR DETAILS)").
- Assignor: Stanford University (as captured in the Google Patents event text).
- Assignee: National Institutes of Health (NIH), U.S. Dept. of Health and Human Services (DHHS), U.S. Government.
- Correspondent: not retrieved.
- Context: government-interest recordation only — not an acquisition, sale, or reorg, and not a transfer of title. This is the standard federally funded (Bayh-Dole) confirmatory license reflecting NIH Grant No. HG00450.
2014-06-17 — No assignment event. "Anticipated expiration"; Google Patents status "Expired – Lifetime." Reel/frame: n/a. Context: term end; ownership still Stanford.
Company/licensing events (NOT assignments of title, and their USPTO recordation is unconfirmed):
- Stanford → Synteni exclusive commercial license (~1994–95).
- Synteni acquired by Incyte Pharmaceuticals (Jan 1998, ~$80 M) — a corporate M&A that carried the license, not the patent title.
- Incyte → Chiron microarray portfolio license (via news release).
- Incyte → Point Technologies sublicense of '522 and '426 (June 2003).
Timeline diagram
timeline
title Ownership of US 6110426
1994 : Priority filing by Shalon and Brown
1995 : Parent application filed
1997 : Continuation application filed
2000 : Patent issues to Stanford
2001 : Incyte asserts as exclusive licensee
2008 : NIH confirmatory license recorded
2014 : Patent expires still Stanford owned
NPE / troll-pattern signals
Baseline evidence used for every call below: Google Patents legal events for US6110426A show exactly one post-issuance recorded event (the 2008-11-17 NIH confirmatory license) and list "Current Assignee: Leland Stanford Junior University." I retrieved no reel/frame for any link. Where a call depends on data I could not retrieve, I say so.
Shell-entity transfer — NOT PRESENT. No LLC assignee of any kind appears in the chain. The only recorded event names NIH/DHHS as the "assignee" of a license, and Google Patents lists Stanford as current assignee. There is no "IP/Holdings/Ventures" suffix, no registered-agent address, no single-member Delaware/Texas LLC anywhere. (Reel/frame not retrieved — call rests on the Google Patents assignee and legal-events fields, not on a reel citation.)
Known asserter in the chain — NOT PRESENT. No Acacia, Marathon, IV, IPNav, Wi-LAN/Conversant, Vringo, Pendrell, MPHJ, Lumen View, Round Rock, Spangenberg entity, or other Unified/RPX high-frequency plaintiff appears as an owner. The one asserter, Incyte Genomics, was a then-operating genomics company and an exclusive licensee, not an assignee. No Unified Patents or RPX asserter-directory hit surfaced for this patent.
Repeat correspondent across the chain — NOT PRESENT / UNKNOWN. I could not retrieve any correspondent of record, so I cannot identify even a single recurring attorney, let alone a pattern. This is a data gap, not a clean bill of health — but there is only one recorded post-issuance event, so the "repeat correspondent across multiple links" pattern cannot exist on this record even in principle.
Cascading transfers — NOT PRESENT. There is no chain of consecutive assignments through LLCs in under 24 months, because there is no chain of assignments at all beyond the (likely) original inventor→Stanford assignment. Assignees do not share a correspondent address because there are no multiple assignees.
Pre-litigation transfer — NOT PRESENT. The first and only assertion naming this patent was filed 2001-11-21 (Incyte v. Invitrogen). No assignment is dated within six months before that date — indeed no title transfer occurred at any point after issuance. Ownership was continuously Stanford's, so no venue/standing-driven transfer was arranged.
Bankruptcy fire-sale — NOT PRESENT. Stanford has never filed Chapter 7/11 and its patent assets were never sold in a proceeding. (Incyte later wound down its microarray business and restructured, but that affected Incyte's license, not Stanford's title — no assignment moved the '426 out of Stanford during any Incyte distress.)
Privateering — NOT PRESENT. The structural analog (university licenses exclusively to a spin-out, which is later acquired by a company that asserts) is not privateering: privateering requires an operating company transferring to an NPE to assert on its behalf. Stanford is a university, not an operating company; and the patent stayed with Stanford — it was never handed to an asserting shell. Marked not present on the evidence available; note this is the single closest factual analog in the chain and is worth a one-line mention in any diligence memo.
Defensive aggregator (anti-NPE) — NOT PRESENT. No RPX, AST, LOT Network, Unified Patents, or Open Invention Network assignment or membership transfer appears. The chain does not terminate at a defensive aggregator; it terminates at the original university assignee and then at expiration (2014-06-17).
Score: zero present, zero unclear-as-to-evidence (one category, correspondent, is un-retrievable). No NPE indicator is supported by the record.
Verdict
Insufficient data — in the taxonomy's own sense of "only the original assignment." Title never moved off the original assignee: the only ownership document in the chain is the presumed inventor→Stanford assignment, and the sole post-issuance recordation (2008-11-17) is an NIH confirmatory license, which is title-neutral. Every one of the eight NPE/troll signals is not present, and Google Patents lists Stanford as current assignee — so this is substantively a no-NPE chain, but I cannot upgrade to a positive "non-NPE" label because I retrieved no reel/frame citations and no correspondent data on which to rest that finding. The patent is also expired since 2014-06-17, which independently removes any live assertion incentive.
Two honest limits on this verdict: (a) I could not execute the USPTO Assignment Center query, so the reel/frame and correspondent fields are genuinely un-retrieved rather than empty; and (b) the closest factual analog to an NPE structure here — a university spin-out taking an exclusive license, later acquired by Incyte, which asserted against Invitrogen — resolves to licensee enforcement by a commercial operating company, not to shell-entity or asserter-chain behavior.
Verify at: USPTO Patent Assignment Search / Assignment Center — https://assignmentcenter.uspto.gov/ (legacy: https://assignment.uspto.gov/patent/index.html) — search property number 6110426 and application 09/001,027, and separately check the parent 08/477,809. Expected results: the original inventor→Stanford assignment (if recorded against the parent) and the 2008-11-17 NIH confirmatory license; no assignment to Synteni, Incyte, or any LLC should appear. Cross-check the Google Patents legal-events tab at https://patents.google.com/patent/US6110426/en and, for the licensor/licensee narrative, Incyte's SEC filings and the June 2003 Point Technologies sublicense report (https://laboratorytalk.com/article/52767/nucleic-acid-array-patent-deal).
Generated 9/10/2026, 6:46:40 PM
Prior art
Earlier patents, publications, and products that may anticipate or render the claims unpatentable.
I'll research the prior art citations for this specific patent. Let me run several targeted searches.
Let me pull the citation data from patent databases directly.
Generated 9/10/2026, 6:45:45 PM
Obviousness
Combinations of prior art that suggest the claimed invention would have been obvious under 35 U.S.C. § 103.
I'll ground a few prior-art facts before building the §103 combinations, since the strength of an obviousness argument depends on what each reference actually teaches and its publication timing relative to the June 17, 1994 priority date.
Key facts confirmed (Abouzied published 1994‑03‑01; Khrapko's 100 µm dot miniaturization; Southern's in‑situ glass arrays). Let me pin down a few more references and check whether the critical "tapping/open‑capillary" element had pre‑1994 analogues.
Obviousness Analysis — US 6,110,426 under 35 U.S.C. § 103
0. Scope, and one flagged contradiction
Claim-text caveat (carry-over from the prior sections). The earlier "Patent summary" explicitly stated the verbatim claim set was not retrievable, while the "Strategic summary" asserted specific claim content ("independent claim 1, the 'tapping the tip of the dispensing device… to break the meniscus' method claim, and independent claim 15"). Those two sections contradict each other, and the authoritative full text supplied here ends mid-sentence in the Detailed Description without claims. I therefore analyze by claimed aspect (the six independent aspects recited in the patent's own Summary of the Invention), not by claim number, and I do not attribute quoted language to any specific claim. Any real § 103 challenge must be run against the literal claim language from Patent Center.
Governing law. Application 09/001,027 was filed 1997-12-30 → pre-AIA § 103(a) applies. The framework is Graham v. John Deere (scope/content, differences, PHOSITA level, secondary considerations) as refined by KSR Int'l v. Teleflex (2007). No Inter Partes Review history exists (per the PTAB section), so no § 315(e) estoppel and no IPR-driven claim narrowing constrain this analysis — every ground below is available to a challenger.
Why the priority date does not save the patent. For the aspects supported by the 1994-06-17 application, the art must predate June 17, 1994 (§ 102(b)). Every reference in the patent's own "References" section predates that date:
| Reference | Publication | Qualifies as § 102(b) art vs. 1994-06-17? |
|---|---|---|
| Kuriyama, An ISFET Biosensor (1989) | 1989 | Yes |
| Maniatis, Molecular Cloning (1989) | 1989 | Yes |
| Lehrach, Genome Analysis Vol. 1, 39‑81 (1990) | 1990 | Yes |
| Khrapko, DNA Sequence 1:375‑388 (1991) | 1991 | Yes |
| Fodor, Science 251:767‑773 (1991) | 1991 | Yes |
| Pirrung, US 5,143,854 | issued 1992 | Yes |
| Bohlander, Genomics 13:1322 (1992) | 1992 | Yes |
| Schena, PNAS 89:3894 (1992) | 1992 | Yes |
| Southern, Genomics 13:1008‑1017 (1992) | Aug. 1992 | Yes |
| Drmanac, Science 260:1649 (1993) | 1993 | Yes |
| Nelson, Nature Genetics 4:11‑18 (1993) | 1993 | Yes |
| Riles, Genetics 134:81‑150 (1993) | 1993 | Yes |
| Abouzied, J. AOAC Int'l 77(2):495‑501 (1994) | 1 March 1994 (verified) | Yes — ~3.5 months before the priority date |
Important reversal of leverage: for subject matter added only in the 1995 CIP (Ser. No. 08/477,809), the effective date is 1995-06-07 — which makes even more art available. So the CIP/continuation structure does not create a priority shield; if anything it broadens the field. Conversely, the parent US 5,807,522 is not usable prior art: it is by the same inventive entity (not "by another" under pre-AIA § 102(e)) and commonly owned (pre-AIA § 103(c) disqualification), and it issued 1998 — after the claimed priority.
A meta-observation. Google Patents' own "Prior art keywords" for this patent are array, microarray, reagent, dispenser, solution. That is a fair decomposition of the claimed subject matter into five pre-existing technical concepts, and it maps almost one-to-one onto the references below. That framing is itself a KSR argument: the claimed invention is a combination of known functional elements, each performing its established function.
1. Combination A — the core "tap-dispense a defined volume" method
Art: Lehrach 1990 + Khrapko 1991 + Abouzied 1994 (+ Maniatis 1989)
| Claimed element (per Summary of Invention) | Where taught |
|---|---|
| Dipping a dispensing element to load a reagent, then transferring it to a defined array position on a support | Lehrach 1990 — "an array of pins dipped into the wells, e.g., the 96 wells of a microtitre plate, for transferring an array of samples to a substrate"; 9,216 spots in 22 × 22 cm |
| Applying a metered, defined volume of an aqueous DNA solution to a defined region of a support, where it remains functional for hybridization | Khrapko 1991 — 5 pmoles of octamer per dot immobilized in a polyacrylamide layer on a glass plate; hybridization performed in 1 µL drops, each exactly covering one dot, giving a "spot with a sharp boundary" |
| Multi-region deposition of reagent on a membrane with hydrophobic compartmentalization of each region | Abouzied 1994 — antibodies "immobilized as multiple lines on nitrocellulose membrane strips and sectored into hydrophobic compartments"; detection by ELISA colorimetry |
| Capillary-action liquid handling and standard DNA immobilization/detection protocols | Maniatis 1989 |
Motivation (KSR prong (iii)/(iv)). The patent's own Background supplies the motivation as an admission: Lehrach's method's "limitation… is that the volume of DNA spotted in each pixel of each array is highly variable." That is a recognized, articulated drawback in the closest art — which is the paradigm case for KSR's "known technique to improve a similar device in the same way." A PHOSITA seeking volume reproducibility would predictably turn to self-metering capillary geometry (the metering principle of every micropipette and capillary in Maniatis and Khrapko), because a liquid column held by surface tension in a narrow channel delivers a volume set by channel geometry rather than by pin-wetting variability. Khrapko further supplies the teaching that such metered volumes of DNA can be deposited on a defined support region and remain hybridizable.
The element that carries the claim — and why it is the fight. The specific limitation of an elongate open capillary channel formed by spaced-apart, coextensive elongate members with a meniscus at the tip, broken by tapping, is not disclosed by any of the listed references. A challenger must fill that gap with one of two theories:
- Analogous-art / common-knowledge: a longitudinal slot between two coextensive tapered blades that holds liquid by capillary action and releases a metered line when touched to a surface is the classic ruling pen / quill / split-nib geometry — a several-centuries-old drafting instrument. Its problem (metering and depositing a small, defined volume of liquid on a defined area of a surface) is reasonably pertinent to the microarray problem, which satisfies the analogous-art test. I could not verify a specific pre-June-1994 split-pin spotting publication in this session (my search returned nothing), so I flag this as an argument a challenger would make, not a citation I can ground.
- "Obvious to try" / design-incentive: given a recognized variable-volume problem in contact spotting, the finite number of known micro-volume deposition mechanisms (solid pin transfer, capillary/pipette, slotted pen, ink-jet/piezoelectric — the last being an express classification of this patent, B01L3/0268) makes selection of an open capillary channel a predictable candidate with a reasonable expectation of success.
Vulnerability of Aspect 1: MODERATE-to-HIGH. Obviousness of the concept is strong; the specific tip geometry + tapping impulse is the narrow point where a patentee has a real (though untested) argument, and where the reproducibility/defined-volume results (2 pL–2 nL, Table 1) can be advanced as unexpected results.
2. Combination B — multiple supports and the wash/reload cycle
Art: Combination A + Maniatis 1989 + the patent's own admitted prior art
The patent's Background concedes the multi-array concept: with Lehrach's pins "the number of arrays that can be made with each dipping is usually quite small" — i.e., one dipping → many arrays was already known; the invention merely increases the number. Dispensing the same reagent at the same corresponding position on each of a plurality of supports is parallel replication of a known spotting step.
The wash → drain → reload sequence is the routine hygiene of any automated reagent-transfer instrument, and Maniatis teaches the necessity of removing residual reagent between steps to avoid cross-contamination. The specification itself describes removal of wash fluid "by vacuum, compressed air spray, sponge, or the like" — the recitation of an unremarkable, exhaustively enumerated set of routine removal techniques is evidence of routine design, not invention.
Vulnerability: HIGH. This is a throughput/parallelism claim built entirely on known process-management steps.
3. Combination C — the automated apparatus
Art: Combination A + Lehrach 1990 (robotic pin spotter) + Kuriyama 1989 + Maniatis 1989
| Claimed element | Where taught / why routine |
|---|---|
| Holder positioning a plurality of planar supports at known positions | Microtitre-plate and membrane-holding fixtures — ubiquitous; Lehrach's robotic ICRF spotting arrays |
| Positioning assembly giving micron-range x/y increments (worm screws, stepper motors) | Standard machine-tool/motion-control art; Lehrach's spotter robot; Kuriyama 1989 (micro-instrumentation, miniaturized sensor arrays) supplies the miniaturization/micro-electronic integration incentive |
| Solenoid-driven tapping actuator | Conventional electromechanical actuation |
| Control unit sequencing loading, positioning, dispensing, washing; multiple dispenser heads for different reagents | KSR: a general-purpose computer/controller performing the routine function of sequencing motions of known mechanical elements is not inventive; multi-head dispensers are the obvious scale-up of Lehrach's pin array |
Motivation. The Background's own admission that pin arrays are slow and limited supplies the throughput incentive; KSR expressly contemplates automation of known manual steps where the art gives a reason to do so and the result is predictable.
Vulnerability: HIGH. This aspect is essentially apparatus-ification of Aspects 1–2.
4. Combination D — dense array of ≥10³ long biopolymers in <1 cm², 0.1 fmol–100 nmol, on polycationic-coated glass
Art: Khrapko 1991 + Southern 1992 + Fodor 1991 / Pirrung US 5,143,854 + Bohlander 1992 + Drmanac 1993
| Claimed limitation | Where taught |
|---|---|
| Array of ≥10³ distinct biopolymers in <1 cm² | Khrapko 1991 expressly designs "miniaturized matrices or sequencing chips… oligonucleotides immobilized within 100 × 100 micron dots disposed at 100 micron intervals" → ~10⁴/cm², squarely inside the '426's own "microarray" definition (10–250 µm regions, ~same spacing, ≥1000/cm²). Fodor 1991 / Pirrung teach still higher densities. |
| Separate, defined (addressable) positions | Khrapko; Southern; Drmanac |
| At least 50 subunits in length | Bohlander 1992 (random-primed PCR of lambda-insert libraries yielding 250–1500 bp products) + Drmanac 1993/Nelson 1993 (clone arrays for hybridization-based mapping) supply both the technique and the reason to use long inserts rather than 8-mers |
| Defined amount 0.1 fmol–100 nmol | Khrapko 1991 — 5 pmoles immobilized per dot; gel capacity ~1 nmole/mm² spot area; probe hybridization at 30 fmoles/dot |
| Support = glass with a polycationic (poly-L-lysine) coating; non-covalent retention under aqueous hybridization | Khrapko 1991 — glass plate bearing a ~30 µm polymeric gel layer carrying nucleic acid; Southern 1992 — nucleic acids on a glass plate surface. The patent itself concedes poly-L-lysine slides "may be obtained commercially, e.g., from Sigma Chemical Co." — i.e., the coated substrate is a prior-art product. Non-covalent (adsorptive) retention of DNA on a membrane by baking/UV is standard Maniatis practice. |
Motivation (KSR prong (ii), substitution of a known element). The poly-L-lysine glass slide is a commercially available article of known function: a positively charged surface that electrostatically adsorbs polyanionic nucleic acid. Substituting a commercially available coated slide for Khrapko's gel-on-glass or Maniatis's membrane is a simple substitution of one known element for another, with a predictable result (DNA adheres; hybridization proceeds). The claim's own numerical ranges (≥10³/cm²; 0.1 fmol–100 nmol; ≥50 subunits) read as the result of routine optimization of parameters Khrapko and Southern already bracketed — which KSR treats as obvious absent unexpected results.
Vulnerability: HIGH, with one qualifier: the non-covalent retention of double-stranded long (≥50-mer) polynucleotides on polycationic glass through 90 °C denaturation and stringent hybridization is the place a patentee can point to a functional surprise. But the patent presents no comparative data against Khrapko/Southern showing this to be unexpectedly better rather than merely different — a gap a challenger will exploit.
5. Combination E — the gridded multi-cell substrate (backing + permeable film + pore-infiltrating raised grid)
Art: Abouzied 1994 + the applicant's own Background admissions (Pall 96-well filter plates; QA Life Sciences gridded membrane; Hyseq hydrophobic grid) + Maniatis 1989
This is the strongest obviousness case in the patent, because the motivation and the solution are both supplied by the applicant and by the admitted art.
- Abouzied 1994 teaches exactly the claimed concept minus the physical barrier: immobilizing reagent in parallel regions on a nitrocellulose sheet, "[s]ectored into hydrophobic compartments to minimize use of reagents," processed as a single sheet. The patent concedes Abouzied "makes the nitrocellulose somewhat hydrophobic using a line drawn with PAP Pen."
- The patent admits the deficiency: "Abouzied does not describe a technology that is capable of completely sealing the pores of the nitrocellulose… assay reagents can leak through the hydrophobic barrier during extended high temperature incubations or in the presence of detergents."
- Pall Corporation's 96-well plate with a porous filter heat-sealed to the bottom (Background-admitted art) teaches precisely the missing element: sealing a porous filter's pores with a barrier so that adjacent wells cannot cross-contaminate. Pall even discloses the heat-seal technique recited in the '426 specification as an alternative barrier method.
- Pall's admitted drawback — "the 96 well plates are at least 1 cm thick and prevent the use of the device for many colorimetric, fluorescent and radioactive detection formats which require that the membrane lie flat" — supplies the express motivation to make the barrier shallow and flat, which is precisely the claimed grid "extending from said backing to positions raised above the surface of said film" (100–2000 µm).
- QA Life Sciences' gridded membrane and Hyseq's hydrophobic-grid "array of arrays" (both Background-admitted) confirm that the array-of-arrays architecture was itself known.
- The '426 specification lists barrier alternatives identical in kind to the art (extruded silicone, wax, thermoset epoxy, UV-cure polymer, silk-screen printing, heat-seal stamping, laminated grid) — an enumeration that reads as routine selection among known materials and application methods.
Motivation (KSR prongs (i) and (iii)). Combine Abouzied's known multi-region membrane + Pall's known pore-sealing filter plate + the recognized need for a flat, thin format = predictable result (separate, non-leaking reaction cells on one sheet). Each element performs its established function; nothing new is attributed to the combination.
Vulnerability: HIGH / very high. The only remaining defense is an argument that "infiltrating the film down to the backing" while raising the barrier above the film surface is a non-obvious structural compromise between Pall's thick plate and Abouzied's surface-only line — a weak position given that both endpoints and the reason to reach the middle are in the art.
6. Combination F — two-color differential gene expression
Art: Schena 1992 + Nelson 1993 / Riles 1993 + Southern 1992 / Khrapko 1991 + Maniatis 1989
- Schena 1992 supplies the biological question and the reagent: the Arabidopsis transcription factor HAT4 placed in a transgenic line at ~10× wild-type level — a system expressly constructed for comparing expression between two cell types.
- Nelson 1993 and Riles 1993 supply arrays of physically mapped clones hybridized to labeled probes, with the array readout resolved to map positions (the yeast karyotype reduction).
- Southern 1992 supplies the express purpose "comparing related sequences and detecting mutation… it should be easy to automate; the quality of the sequence results can be evaluated statistically."
- Maniatis 1989 supplies reverse transcription, incorporation of labeled nucleotide analogs, and hybridization/wash protocols.
- Khrapko 1991 supplies quantitative, calibrated hybridization signal from individual array dots (dissociation curves, normalized matrices), i.e., the notion that arrayed signals can be measured and compared.
Motivation. Comparing expression between two cell states is the stated purpose of the arrayed-clone art; using two spectrally distinguishable labels in the same hybridization provides an internal control that cancels spot-to-spot variation in immobilized amount and hybridization efficiency — a benefit a PHOSITA would recognize and expect, using known fluorophores and known dual-label hybridization technique. Under KSR's "obvious to try," the number of identified, predictable solutions to the problem of comparing two expression states on one array was small.
Vulnerability: MODERATE. This is the aspect with the best non-obviousness story: the specific insight that a mixed two-color probe read as a ratio/color would convert a qualitative array into a quantitative differential-expression instrument is a genuine conceptual step, not a mere substitution. It is also the aspect with the strongest secondary-considerations record (see § 8). But note a counter-lever: Southern 1992 already frames array hybridization as a method for "comparing related sequences," which a challenger will use to argue the comparative purpose was known.
7. Summary — vulnerability ranking
| Aspect | Best combination | KSR rationale | Vulnerability |
|---|---|---|---|
| Multi-support + wash/reload | A + Maniatis | Routine parallel replication; routine cleaning | Highest |
| Automated apparatus | A + Lehrach + Kuriyama | Automation of known manual steps | Very high |
| Gridded multi-cell substrate | Abouzied + Pall + QA + Hyseq | Known elements to remedy an admitted, articulated defect; known technique improving known device | Very high |
| Dense non-covalent polylysine array | Khrapko + Southern + Fodor/Pirrung + Bohlander | Substitution of commercially available coated slide; obvious optimization of ranges | High |
| Core tap-dispense method | Lehrach + Khrapko + Abouzied | Recognized defect (volume variability) → predictable use of capillary metering | Moderate–High (turns on split-nib/tapping teaching) |
| Two-color differential expression | Schena + Nelson/Riles + Southern + Maniatis | "Obvious to try"; internal-control benefit recognized | Moderate |
8. Secondary considerations a patentee would assert — and how each is countered
- Unexpected results. (a) Defined volumes of 2 pL–2 nL with repeatability, against Lehrach's admittedly "highly variable" volumes — strongest, but arguably an anticipated benefit of self-metering capillary geometry. (b) Non-covalent retention of long PCR products on poly-L-lysine glass through denaturation — potentially strong, but unsupported by comparative data against Khrapko/Southern in the patent.
- Long-felt need / failure of others. Genuine: the art's own statements (Lehrach's variability; Southern's "further development is needed before the method can be used routinely") show the need was recognized and unmet. A challenger answers with KSR's caution that a need, once the elements are known, does not make the combination non-obvious.
- Commercial success / licensing. Relevant: the technology was commercialized via Synteni and later Incyte, and in June 2003 Incyte sublicensed US 5,807,522 and US 6,110,426 (Point Technologies "Accelerator" pins) — a licensing program proving market value. Nexus caveat: that success may be attributable to the combination of all aspects (particularly the two-color assay) rather than to any single challenged limitation, which the patentee must show.
- Copying / industry uptake (Affymetrix, Incyte, and the wider microarray industry using split-pin spotting) — probative, but co-extensive with independent development, which KSR treats as a counter-indication of non-obviousness.
9. Bottom line
Under pre-AIA § 103(a) and KSR, US 6,110,426 is vulnerable across most of its disclosed subject matter, with the strength of the challenge increasing as the claim moves away from the two-color differential-expression concept and toward the mechanical/architectural aspects. The best single-reference-plus-secondary-reference packages are:
- Lehrach 1990 + Khrapko 1991 + Abouzied 1994 (optionally + Maniatis 1989) — attacks the core method and multi-support aspects; the motivation is supplied by the patent's own admission that Lehrach's spotted volumes are "highly variable."
- Abouzied 1994 + Pall/QA/Hyseq (applicant-admitted art) — attacks the gridded multi-cell substrate; motivation supplied by the patent's own admission that Abouzied fails to seal the pores, with Pall teaching pore-sealing and the flat-format incentive.
- Khrapko 1991 + Southern 1992 + Fodor 1991 / Pirrung US 5,143,854 + Bohlander 1992 — attacks the sub‑1 cm², ≥10³-feature, ≥50-subunit, polycationic-glass aspect.
- Schena 1992 + Nelson 1993 / Riles 1993 + Southern 1992 + Maniatis 1989 — attacks the two-color method, but this is where a patentee's best defense and best secondary-considerations evidence lie.
Practical notes. (i) Because there is no IPR history, nothing is estopped and all of the above, plus art never before the Examiner, remains available. (ii) The patent expired 2014-06-17, which is why the obviousness question is academic today — but the analysis matters for the family's later members (e.g., US 7,323,298 B1) and for any historical-validity determination. (iii) The ranking above rests on the aspect-level disclosure, not on verified claim language — before relying on any of it, obtain claims 1–20 from USPTO Patent Center and re-map each limitation.
Sources: full patent text supplied in this prompt; Abouzied & Pestka, J. AOAC Int'l 77(2):495‑501 (1 March 1994) (verified publication date and "sectored into hydrophobic compartments"); Khrapko et al., DNA Sequence 1:375‑388 (1991) (verified 100 × 100 µm dots at 100 µm intervals; 5 pmol/dot; 1 µL drop per dot); Southern, Maskos & Elder, Genomics 13(4):1008‑1017 (Aug. 1992) (in‑situ oligonucleotides on a glass plate; "comparing related sequences and detecting mutation"); Lehrach et al., Genome Analysis Vol. 1, 39‑81 (1990) (pin-based 9,216-spot arrays); Google Patents US6110426A.
Discrepancy noted: the task header states April 26, 2026, while the session metadata gives September 10, 2026. Neither date affects this analysis (the patent expired June 17, 2014 under either).
Generated 9/10/2026, 6:47:05 PM
Extensions
Patent term adjustments, term extensions, continuations, divisionals, family members, and expiration dates.
Derivative works
Defensive disclosure: derivative variations of each claim designed to render future incremental improvements obvious or non-novel.
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This patent in court (1)
1 tracked lawsuit name US 6110426.