Invalidity dossier
US 6410231
SNP detection
Current assignee: Incyte Corp
Added 9/26/2026, 8:12:38 AM
Active provider: DeepSeek · deepseek-flash
Patent summary
Title, assignee, inventors, filing/issue dates, abstract, and a plain-language overview of the claims.
I'll search for this patent number and any 2026 CAFC docket activity.
Let me check for litigation/docket activity and confirm the full claim set.
US Patent 6,410,231 — Summary
Bottom line up front: I confirmed the bibliographic data from the full patent text and corroborating databases. I found no litigation, PTAB, or CAFC docket activity in 2026 (or any year) involving US 6,410,231. I did find a 2026 Incyte case in the District of New Jersey, but the patents in that case relate to ruxolitinib, not this patent. Uncertainty details are flagged at the end.
Bibliographic data
| Field | Value |
|---|---|
| Patent number | US 6,410,231 B1 (interpreted literally; no other number substituted) |
| Title | "SNP detection" |
| Inventors | Lyle Arnold; Thomas Theriault; Tod Bedilion |
| Original assignee | Incyte Genomics Inc (assignment recorded 1999-02-26 to Incyte Pharmaceuticals, Inc.) |
| Current assignee (as listed) | Incyte Corp — Google Patents notes listed assignees may be inaccurate |
| Application no. | US 09/259,898 |
| Filing / priority date | 1999-02-26 |
| Issue date | 2002-06-25 |
| Legal status | Expired – Fee Related; anticipated expiration 2019-02-26 |
| PCT / foreign family | PCT/US2000/004876 → WO 2000050869 A2; EP 1166076 A4; AU 755398 B2; CA 2362619 A1; JP 2002537780 A |
| Later family member | Continuation US 10/178,318 → US 2003/0059813 A1 |
| Classifications | C12Q 1/6827 (hybridisation assays for mutation/polymorphism); C12Q 1/6837 (probe arrays/chips) |
Abstract (as published)
The invention provides methods, compositions and systems for detecting multiple single nucleotide polymorphisms (SNPs) in a population of target polynucleotides in parallel in a sandwich assay employing SNP probes, capture polynucleotides and, optionally, auxiliary polynucleotides. The relative affinities of the SNP probes for the corresponding SNP regions can be increased with reagents which normalize the melting temperatures of the probes and/or by positionally facilitating interactions between the SNP probe, the SNP region, the capture polynucleotide and/or the auxiliary polynucleotides, such as through a minor groove binder. The probes may comprise a degenerate set of all possible same-sized polynucleotides and the capture polynucleotides are generally immobilized and arrayed at corresponding discrete elements in high density.
Independent claims — plain language
The patent as retrieved (FreePatentsOnline) carries claims 1–17, with two independent claims (1 and 16); claims 2–15 and 17 are dependent.
Claim 1 — the core "sandwich" SNP-detection method
A method of detecting multiple SNPs in parallel by mixing three things together in one reaction:
- Target polynucleotides (from a sample) — each has (i) a capture region and (ii) a SNP region containing the SNP of interest;
- Capture polynucleotides — each is immobilized at its own discrete spot on a substrate (an array) and is complementary to a corresponding capture region, so each target gets "caught" at its own address on the array; and
- SNP probes — each complementary to a corresponding SNP region and able to hybridize selectively.
Then you detect where the SNP probes landed on the substrate. Signal from a given probe at a given spot = that SNP is present in the corresponding target. In other words: array-capture the target, then allele-specifically label it with a probe, and read the array.
Claim 16 — the two-probe-pair / quantitative-discrimination version
A parallel multiplex SNP method using assay probe pairs — a "first" SNP probe perfectly complementary to the SNP region, and a "second" SNP probe with a single-base mismatch to the same region. The capture step provides a "first discrimination" of the sample; then the discriminating conditions — either (a) a reagent that normalizes melting temperatures of the probes, and/or (b) the SNP probe interacting with the capture polynucleotide or an auxiliary probe — provide a "second discrimination." The claim requires the match:mismatch hybridization ratio to increase at least 2-fold under those conditions.
Notable dependent claims (context, not independent scope):
- 2/11: SNP probes are a degenerate set of all possible same-sized polynucleotides (the "universal detector set")
- 3/12: sample is fragmented genomic DNA
- 4/13: captures are from a segregated, arrayed cDNA library
- 5/14: high-density arraying of capture polynucleotides
- 6/15: SNP probes carry a label
- 7: enhanced discrimination between the true SNP region and other regions
- 8: melting-temperature-normalizing reagent
- 9: interaction with the capture or an auxiliary probe
- 10: the interaction is via a minor groove binder (MGB) tethered to the SNP probe, capture polynucleotide, or auxiliary probe
- 17: (as retrieved) "The method of claim 10, wherein the assay probes comprise a degenerate set…" — see caveat below
Technical context (from the specification)
- The MGB workhorse exemplified is CDPI₃ (1,2-dihydro(3H)-pyrrolo[3,2-e]indole-7-carboxylate, Lukhtanov et al., Bioconjugate Chem. 1995, 6, 418–426); other MGBs named are netropsin, distamycin, CC-1065.
- Examples use ApoE polymorphic sites 858 (A/G) and 448 (T/C); cyanine dyes Cy3/Cy5 (and Cy2/Cy7 in the universal set) as differential labels.
- Example 3 reports the MGB-conjugated 11-mer probes increased the Cy3:Cy5 (match:mismatch) ratio at least 10-fold versus the 15-mer probes of Example 1.
- Modifications A and B address spurious universal-detector binding on the non-SNP side: (A) 2′-O-methyl ribonucleotides at the capture terminus distal to the SNP, which block MGB binding; (B) designing the capture/target hybrid to be blunt-ended away from the SNP.
Litigation / docket check (USPTO + CAFC 2026)
- USPTO: No assignment or post-grant activity beyond ordinary prosecution/assignment was surfaced. Status is Expired – Fee Related (lapsed at the 2019-02-26 anticipated expiration).
- CAFC 2026 dockets: I found no Federal Circuit docket, appeal, or oral-argument listing involving 6,410,231. Searches returned unrelated hits that merely contain the digit string (e.g., a Brazilian court document index number, a Canadian chart correction ID, a drone telemetry latitude reading).
- 2026 Incyte district-court activity (NOT this patent):
Incyte Corp. et al. v. Zydus Lifesciences Ltd., D.N.J. 2:26-cv-06562, filed 2026-06-04; andIncyte Corp. et al. v. Alkem Laboratories Ltd. et al., 1:26-cv-02338. These are Incyte patent-enforcement actions, but the reported patents-in-suit are the ruxolitinib/JAK-inhibitor family (e.g., US 7,598,257; 8,415,362; 8,722,693; 8,822,481; 8,829,013) — not US 6,410,231. I found no pleading in these or any other case asserting 6,410,231. - Citation footprint instead of litigation: 6,410,231 is widely cited as prior art/background by later patents, e.g. EP 1506316 B1 [0072], EP 1718770 B1 [0076], EP 3277836 B1 [0064], EP 3052656 B1 [0002], and WO 2005121359 A1, which cites the WO 00/50869 family member as "X" art against claims 1–9, 12, 20–22, 27, 29, 30.
Uncertainty and caveats
- Claim count/dependency: The authoritative full text supplied to me omits the claims section. My claims summary is drawn from FreePatentsOnline's rendering. Claim 17 there reads "The method of claim 10…", which is anomalous for a claim immediately following independent claim 16 and may be an OCR/transcription artifact (it may in fact depend from claim 16). I have not auto-corrected it; treat claim 17's dependency as unverified.
- Assignee: "Current Assignee: Incyte Corp" is Google Patents' listing, which explicitly disclaims accuracy; the recorded original assignee is Incyte Genomics Inc, with the 1999-02-26 assignment to Incyte Pharmaceuticals, Inc.
- No litigation found ≠ no litigation exists. PACER/CAFC docket coverage for very old, expired patents is often not indexed by general web search. I could not access PACER or the CAFC docket system directly, so I cannot rule out a docket I did not surface. If you need a definitive negative, a direct PACER/RECAP and CAFC CM/ECF query on the exact string "6,410,231" is required.
Generated 9/27/2026, 10:31:58 PM
Cases on file (0)
Specific litigation cases in our database that name US patent 6410231. The free-form analysis below may also discuss cases beyond this list.
No cases on file mention this patent. Upload a CSV or add a case manually in Admin → Manage litigation cases.
Litigation summary
Past and pending lawsuits — plaintiffs, defendants, jurisdictions, outcomes, and notable rulings.
I'll research litigation involving US patent 6410231. Let me run several searches.
Let me search litigation-specific databases.
Litigation Search: U.S. Patent No. 6,410,231
Bottom line
I found no litigation — district court, Federal Circuit, PTAB, or ITC — in which U.S. Patent No. 6,410,231 ("SNP detection") was asserted or challenged. Searches of the sources available to me (Google Patents legal-events tab, Unified Patents litigation portal queries, Justia/Docket Alarm/UniCourt dockets, CourtListener, and general web searches for the patent number as an asserted patent) returned no case records tied to this patent. I cannot produce a plaintiff/defendant/case-number table because no such case appears in the records I could reach.
Patent identification (confirmed literal)
- Patent: US 6,410,231 B1 — "SNP detection"
- Inventors: Lyle Arnold; Thomas Theriault; Tod Bedilion
- Original assignee: Incyte Genomics, Inc. (assignment recorded 1999‑02‑26 to Incyte Pharmaceuticals, Inc.)
- Current/last assignee of record: Incyte Corp.
- Application: US 09/259,898
- Priority/filing date: 1999‑02‑26
- Grant date: 2002‑06‑25
- Family: EP 1166076 A4; AU 755398 B2; JP 2002537780 A; CA 2362619 A1; PCT/US2000/004876 (WO 2000050869 A2); continuation US 2003/0059813 A1 (from US 10/178,318, filed 2002‑06‑24)
- Status: Expired – Fee Related; anticipated expiration 2019‑02‑26
Important negative-evidence context (not this patent)
Searches surfaced adjacent Incyte/Affymetrix litigation, but the patents in suit there were not the '231 patent. I flag these only to preempt confusion — they should not be reported as '231 litigation:
- Affymetrix v. Synteni/Incyte (D. Del.) — transfer/venue opinion referencing the '994, '305, and '992 patents and the GEM array. The '231 patent is not referenced as a patent in suit.
- Incyte Genomics–Affymetrix settlement (Dec. 21, 2001) — the announcement states the second suit involved Incyte's RNA amplification patents U.S. 5,716,785 and 5,891,636, with a broad cross-license. The '231 patent issued June 25, 2002 — after that settlement — and is not named.
- Numerous Incyte v. generic manufacturers (D.N.J.) ANDA cases (e.g., Zydus, Hikma, Alkem, Apotex, Sun Pharma) concern Incyte's later small-molecule/API patents (e.g., ruxolitinib and deuruxolitinib families), not the '231 SNP-detection patent.
Caveats on completeness
- The patent's classification (C12Q 1/6827 – hybridisation assays for mutation/polymorphism) and its expiration-for-nonpayment status make it an unlikely assertion candidate, which is consistent with the empty result.
- I was not able to load a dedicated Unified Patents case-list page filtered to this patent, nor Docket Navigator or RPX Insight directly. Recommend confirming on those paid/portal sources before treating this as conclusive.
- Under the operating rule to interpret identifiers literally: none of the non-patent hits for the string "6410231" (a Brazilian TRF‑1 administrative order, a Czech contract-registry entry, a Chinese utility-model listing, an FDA MAUDE device sequence number, a PMID, etc.) are litigation involving U.S. Patent 6,410,231.
Suggested verification steps
- Unified Patents litigation portal — filter patents to "6410231" (
https://portal.unifiedpatents.com/litigation/caselist?patents=6410231). - RPX Insight / Docket Navigator — search by patent number.
- PACER Case Locator — search "6,410,231" across district courts.
- USPTO Patent Center / Global Dossier — verify no recorded litigation or assignment of a cause of action.
If you need, I can attempt a more targeted portal query once a working endpoint is available.
Generated 9/27/2026, 10:31:53 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.
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.
PTAB / AIA Trial Review — U.S. Patent No. 6,410,231 ("SNP detection")
Data provenance note: The canonical source for this section is the structured "PTAB proceedings on file" block supplied in this prompt, which reflects the USPTO Open Data Portal (ODP) / PTAB API ingest. That block returns no AIA trial proceedings for US 6,410,231. I independently searched for petitioner filings, claim-level outcomes, FWDs, settlements, and CAFC appeals (see searches listed in the Recommended Next Steps section) and surfaced nothing connecting this patent to any IPR, PGR, or CBM. The sections below therefore report the absence, and — importantly for a defendant — the near-miss patent numbers that a careless search will surface and that you must not conflate with this patent.
Proceedings overview
Total AIA trial proceedings on file: 0 — 0 active, 0 claims invalidated, 0 claims sustained, 0 settled, 0 institution denials; the patent's bottom-line defensive posture is therefore unusual and stronger than any PTAB outcome: US 6,410,231 is a pre-AIA patent that expired on 2019-02-26 for failure to pay maintenance fees ("Expired – Fee Related"), so no PTAB challenge was ever needed and any demand letter citing it today is asserting an expired, unenforceable-in-practice right whose § 286 damages lookback window (six years before filing) falls entirely after the patent's expiration date.
Proceedings (most-impactful first)
None. There is no AIA trial proceeding to list.
No IPR, PGR, or CBM petition number, institution decision, Final Written Decision, termination, or Federal Circuit appeal exists for this patent on the record available to me. I will not invent a proceeding number to fill this slot. For completeness, the adjacent USPTO record is:
- Patent: US 6,410,231 B1, "SNP detection"
- Inventors: Lyle Arnold, Thomas Theriault, Tod Bedilion
- Original assignee: Incyte Genomics, Inc. (assignment recorded 1999-02-26 to Incyte Pharmaceuticals, Inc.; current assignee listed as Incyte Corp)
- Application 09/259,898; filed 1999-02-26; granted 2002-06-25; 20 claims
- Family: PCT/US2000/004876 → WO 2000/050869 A2 (published 2000-08-31); EP 1166076 A4; CA 2362619 A1; JP 2002-537780 A; AU 755398 B2; continuation US 10/178,318 → US 2003/0059813 A1
- Legal status: Expired – Fee Related; anticipated expiration 2019-02-26 (20 years from the 1999-02-26 filing date)
- Technology classification: C12Q 1/6827 (hybridisation assays for detection of mutation or polymorphism); C12Q 1/6837 (probe arrays/chips)
Source: Google Patents — US6410231B1.
Strategic summary
Claim status. All claims 1–20 stand exactly as granted — not because they survived a PTAB attack, but because they were never attacked. There are no CANCELED claims and no claims narrowed by certificate. Claim 1 (the "first discrimination / second discrimination" sandwich-assay method) and claim 16 (the probe-pair embodiment requiring at least a 2-fold matched:mismatch hybridization ratio) are the two independent claims; claims 2–15 depend from claim 1 (claims 7–15 depending from claim 7) and claims 17–20 depend from claim 10. This is what the printed patent says — there is no FWD to quote, because none exists. The real limiting fact is temporal, not adjudicative: the patent term ran out on 2019-02-26.
Estoppel landscape. Because no IPR/PGR was ever instituted, 35 U.S.C. § 315(e)(2) estoppel is completely absent. No petitioner, real party in interest, or privy is barred from anything. Every prior-art ground — patents, printed publications, § 102(a)/(b)/(e)/(g) art, public use, on-sale, § 112 written description/enablement, and § 101 eligibility — remains fully available in district court, and every patent-or-printed-publication ground remains available in a fresh IPR. Note the flip side for a defendant: this patent's own specification was published as WO 2000/050869 A2 on 2000-08-31, and that publication is already being cited as prior art (X and A citations) against other parties' later applications — e.g., the EPO/KIPO search reports in the results above cite "WO 0050869 A2 (INCYTE PHARMA. INC.), 31 August 2000 … claims 1 to 4, and figure 1" against unrelated later filings, with "US 6410231 B1, 25 June 2002" listed as a family member. In other words, the disclosure here is a usable prior-art weapon in both directions.
Pattern signals. None of the classic patterns are present: there is no serial petitioner, no patent-owner PTAB-appeal campaign, and no defensive aggregator (no Unified Patents, RPX, or similar entity) in the chain. The patent owner's historical enforcement activity was the 1998–2001 Affymetrix/Synteni/Incyte microarray litigation, which settled by a comprehensive cross-license announced 2001-12-21 involving Affymetrix patents (U.S. 5,445,934; 5,744,305; 5,800,992; 5,871,928; 6,040,193) and Incyte's RNA-amplification patents (U.S. 5,716,785; 5,891,636) — 6,410,231 was not one of the asserted patents, and the Affymetrix litigation had already concluded before this patent issued on 2002-06-25. See Incyte press release, "Affymetrix and Incyte Genomics Settle All Patent Infringement Litigation," 2001-12-21.
⚠️ Near-miss numbers — do not conflate. Generic searches for "the '231 patent" return a large volume of unrelated PTAB and CAFC material that does not involve US 6,410,231. I verified each of the following is a different patent, and none of them should appear in a clearance memo about this patent:
| Look-alike | What it actually is |
|---|---|
| U.S. 6,232,231 | Semiconductor trench/polishing patent, subject of IPR2020-00603 |
| U.S. 8,664,231 | Methotrexate formulation patent, subject of IPR2016-01370 |
| U.S. 10,301,231 | MicroSource/related patent; claims 1–4 held obvious on SJ in N.D. Iowa |
| U.S. 6,611,231 | XR Communications (Vivato) wireless patent; claims 1–9, 12 held indefinite by N.D. Cal., aff'd, Fed. Cir. 2022-1125/2022-1141 (2023-05-18) |
| U.S. 10,548,641 | Bone-anchor patent cited in a double-patenting rejection |
Source for the consolidated look-alike check: USPTO PTAB petition documents at ptacts.uspto.gov (e.g., petitions 1533479, 1555287, 1558397) plus Fed. Cir. opinion text in the search results; each identified the patent under review by full number, confirming none is 6,410,231.
Recommended next steps
1. If you are a defendant facing an assertion of US 6,410,231 — lead with expiration, not invalidity.
The patent's legal status is "Expired – Fee Related," with anticipated expiration 2019-02-26. Because the exclusive right ended in 2019 and 35 U.S.C. § 286 caps damages at six years before suit, a complaint filed on or after 2025-02-26 has no reachable infringement period at all. Pull the maintenance-fee history and any 37 C.F.R. § 1.362 expiration notice from USPTO Patent Center and confirm no petition to revive was granted (revival after § 1.362 expiration is not available for an unintentionally-lapsed patent whose term has run). Then confirm the current owner of record via USPTO Assignment — Google Patents lists the current assignee as Incyte Corp and the original assignee as Incyte Genomics Inc, so a demand letter from anyone else needs a recorded chain of title.
2. There is no FWD to cite, so don't pretend there is.
I searched for a Final Written Decision, institution decision, termination, or CAFC appeal and found none. If opposing counsel asserts that "the PTAB already invalidated" any claim of this patent, that representation is false as to US 6,410,231 — make them produce the proceeding number. I can state this affirmatively because the ODP-sourced canonical list returns zero proceedings, and no web source contradicts it.
3. If your real interest is the technology (SNP sandwich assays, MGB-tethered detectors, universal detector sets), treat the specification as art, not as a threat.
WO 2000/050869 A2 published 2000-08-31, and the patent itself issued 2002-06-25. Either is § 102(b) art against later-filed applications claiming array-based SNP detection with minor-groove-binder stabilization (CDPI₃, netropsin, distamycin, CC-1065) or degenerate "universal detector" probe sets. The searches above show the EPO and KIPO have already used this family exactly that way.
4. Residual risk to close out.
Two things I could not fully exclude, and you should verify directly rather than rely on my searches:
- An ex parte reexamination (90/xxxxxx) or pre-AIA inter partes reexamination filed against this patent between 2002 and 2012. My searches for a reexamination control number tied to 6,410,231 returned nothing, but ex parte reexam is anonymous and is not part of the AIA-trial data set — check the "Child Continuity Data" tab in Patent Center.
- A recently filed proceeding not yet indexed by ODP. The API ingest lags live filings. Search PTAB E2E and the PTAB Decisions database by patent number before you rely on the zero count in a brief or an opinion letter.
Bottom line for the defendant: no AIA trial proceeding exists, and the absence here is not the usual "not-yet-challenged" signal — it is the signal of a patent that reached its 2019-02-26 expiry without ever being worth an IPR. Litigation-grade validity risk and § 315(e)(2) estoppel do not apply; expiration and § 286 do.
Generated 9/27/2026, 10:32:09 PM
Ownership chain (1)
Asserters network →Structured records extracted from the assignment-history narrative below. Each entity links to its full ownership-network profile.
1999-02-26 · Assignment
Lyle Arnold; Tod Bedilion; Thomas TheriaultINCYTE PHARMACEUTICALS, INC.
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 start by pulling the assignment-side data for this patent from the sources available.
The assignment records aren't surfacing in generic search. Let me probe the assignment databases and Incyte's corporate history directly.
Good corporate-history context. Now let me look for litigation/assertion activity and any post-2003 transfers involving this patent.
Data-access caveat (read first)
I could not retrieve reel/frame-level records for US 6,410,231. assignmentcenter.uspto.gov and assignment.uspto.gov are JavaScript-driven and were not queryable through the research tools available to me, and no indexed page surfaced the reel/frame numbers, recording dates, or correspondent of record for this patent. No reel/frame numbers, execution dates, or correspondent names are asserted below unless they appear in a source I actually retrieved. Anything I could not verify is labeled as a gap rather than filled in. Verification link: https://assignment.uspto.gov/patent/index.html#/patent/search/results?q=[6410231](/patent/6410231)
Inventors
| Inventor | Employer at filing | Basis |
|---|---|---|
| Lyle Arnold | Incyte Pharmaceuticals, Inc. (Palo Alto, CA) | Named as assignor to Incyte Pharmaceuticals, Inc. in the recorded assignment-of-interest event dated 1999-02-26 |
| Thomas Theriault | Incyte Pharmaceuticals, Inc. | Same |
| Tod Bedilion | Incyte Pharmaceuticals, Inc. | Same |
All three executed the assignment to Incyte Pharmaceuticals, Inc. on the filing date (1999-02-26), i.e. an at-filing, employer-assignment — the normal pattern for a corporate genomics R&D shop, not a founder-retained portfolio.
Unusual-pattern check: Not determinable. The premise I'd look for — all inventors leaving the assignee within 12 months of filing as a precursor to a portfolio sale — cannot be assessed: I found no inventor-departure records, and for the relevant period Incyte was expanding its genomics headcount (it built the Incyte Genetics unit in Aug 1998 and ramped SNP-discovery programs through 1999). The one verifiable personnel change is at the executive level: Incyte replaced senior management with a drug-development team in November 2001, and shut the Palo Alto site and laid off 257 employees, including patent staff, in February 2004 (Winston & Strawn case-study deck, The Case of Incyte Genomics, Sept 2005). Those are organizational exits, not inventor exits, and they post-date this patent by 2–5 years.
Original assignee
On the issued face: Incyte Genomics, Inc. (per Google Patents "Original Assignee" and FreePatentsOnline's assignee block for US 6,410,231). The assignment actually recorded at filing ran to Incyte Pharmaceuticals, Inc., which is the same company: Incyte Pharmaceuticals, Inc. → Incyte Genomics, Inc. (name change effective 2000-07-07; the WSGR deck and an Incyte 10-Q header dated 2001-05-08 read "INCYTE GENOMICS, INC. (Formerly Incyte Pharmaceuticals, Inc.)").
- Primary line of business: Incyte was an operating genomics/bioinformatics company — it synthesized and sold proprietary sequence databases (LifeSeq, ZooSeq, BioKnowledge), ran microarray gene-expression services (GEM, via its January 1998 Synteni acquisition), sold clones and reagents, and licensed its patent estate. The 2002 10-K explicitly describes "revenues from licenses to a range of intellectual property… including… microarray fabrication and gene expression" and "licensing of our extensive gene patent portfolio for use by genomic 'tool' and service providers."
- Product embodying the claims: Partly. Incyte commercially offered array-based hybridization/expression services and licensed array-related patents; the claimed sandwich SNP-genotyping assay itself was not sold as a commercial kit. Incyte's own 1999–2001 SNP work sat inside the Incyte Genetics unit that was recombined into the main business in Feb 1999, not spun out.
- Assertion posture: Incyte was not solely a licensor — it was a litigating operating company. Incyte sued Invitrogen on 2001-11-21 in S.D. Cal. asserting thirteen of Incyte's own patents and seeking treble damages; it settled microarray litigation with Affymetrix on 2001-12-21; and it licensed array patents to Agilent (announced 2002-03-18). I could not confirm that US 6,410,231 was among the thirteen patents asserted against Invitrogen — that requires the complaint docket, which I did not retrieve.
- Current status: Operating. Incyte Genomics, Inc. renamed to Incyte Corporation (effective 2003-03-15) and the company remains an active NASDAQ-listed drug developer (INCY) as of 2026. No dissolution, no bankruptcy, no wind-up.
Assignment timeline
What I can substantiate at the patent level is a single recorded assignment, plus corporate name changes that are documented in SEC filings but not confirmed as separately recorded against this patent:
1999-02-26 (executed) / recorded 1999-02-26 per Google Patents legal events — Reel/Frame not retrieved
- Conveyance: Assignment of assignors' interest (the assignment-of-interest record, per "ASSIGNMENT OF ASSIGNORS' INTEREST (SEE DOCUMENT FOR DETAILS)" on the legal-events timeline)
- Assignor: Lyle Arnold; Tod Bedilion; Thomas Theriault
- Assignee: Incyte Pharmaceuticals, Inc.
- Correspondent: not retrieved — data gap. (Do not read the absence as "no correspondent"; every recorded assignment has one.)
- Context: at-filing employment assignment — inventors conveyed to their employer on the day the application was filed.
2000-07-07 — not confirmed as a recorded assignment; corporate name change only
- Conveyance (if recorded): Change of Name
- Assignor: Incyte Pharmaceuticals, Inc.
- Assignee: Incyte Genomics, Inc.
- Correspondent: not retrieved
- Context: change of name only — no change in beneficial ownership. Confirmed from SEC filings and a corporate name-change table; I did not confirm a US patent-assignment record for this transition on this patent.
2003-03-15 — not confirmed as a recorded assignment; corporate name change only
- Conveyance (if recorded): Change of Name / merger into parent
- Assignor: Incyte Genomics, Inc.
- Assignee: Incyte Corporation
- Correspondent: not retrieved
- Context: change of name only. Google Patents lists "Current Assignee: Incyte Corp" while "Original Assignee: Incyte Genomics Inc" — that divergence is consistent with a later Incyte-side record, but I could not pull reel/frame to confirm whether it is a recorded change-of-name, a merger record, or Google's own corporate-tree inference.
2002-06-24 — not an assignment. Google Patents records "Priority to US10/178,318," which is a continuation application (published as US 2003/0059813 A1, 2003-03-27), not a transfer. No separate assignee is recorded for the continuation in the sources I reached. Family members US 6,410,231 / AU 755398 B2 / CA 2362619 A1 / EP 1166076 A2 / JP 2002-537780 A / WO 00/50869 A2 are prosecution family, not ownership events.
Bottom line on the chain: there is no post-issuance transfer of record that I could verify for US 6,410,231. If the Assignment Center confirms this, the finding is that the original assignee family still owns the patent — and, per Google Patents legal status, the patent is "Expired – Fee Related," i.e. it lapsed for non-payment of maintenance fees (3.5/7.5/11.5-year fees would have fallen due 2005-12-25, 2009-12-25, 2013-12-25 against a 2002-06-25 grant), with the nominal 20-year term ending 2019-02-26. A fee-lapsed patent that was never transferred is about as strong a non-assertion signal as the record can produce.
Non-evidence, flagged to prevent a false correspondent match: Incyte Pharmaceuticals' securities counsel of record on its March 1999 S-3 was Stanton D. Wong, Pillsbury Madison & Sutro LLP, San Francisco. That is an SEC filing contact, not an assignment correspondent, and must not be treated as a correspondent hit for this chain.
Timeline diagram
timeline
title Ownership of US 6410231
1999 : Application filed 26 Feb 1999
: Assigned to Incyte Pharmaceuticals Inc
2000 : Assignee renamed Incyte Genomics Inc
2002 : Patent granted 25 Jun 2002
2003 : Company renamed Incyte Corporation
2004 : Genomics patent program wound down
2019 : Nominal 20 year term ends
NPE / troll-pattern signals
Shell-entity transfer — Not present. No assignment to any "IP / Holdings / Licensing / Ventures" entity appears anywhere in the record I could reach. Current assignee of record remains the Incyte corporate family; there is no single-purpose LLC, no registered-agent-service address, and no Delaware/Texas shell in the chain.
Known asserter in the chain — Not present. No assignee in the chain matches any of the listed NPEs (Acacia, Marathon, IV, IPNav, Wi-LAN, Mosaid/Conversant, Vringo, Pendrell, Innovatio, MPHJ, Lumen View, Round Rock, Document Generation Corp, Spangenberg entities). Neither RPX nor Unified Patents surfaced this patent in any assertion campaign in my searches. The only litigant in the family's history is Incyte itself, and it litigated as a practicing company (Invitrogen, 2001-11-21; Affymetrix settlement, 2001-12-21) while simultaneously selling database subscriptions to 100+ customers.
Repeat correspondent across the chain — Unclear / not assessable. This is the signal I was specifically asked to capture, and I must report it as a data gap: I retrieved no correspondent names for any link, so I cannot test for recurrence. There is only one confirmed recorded link, so even a successful retrieval would likely show a single correspondent at most — recurrence requires ≥2 links, which the record does not appear to have.
Cascading transfers — Not present. No consecutive chained assignments; no two transfers within 24 months; nothing through chained LLCs. The only same-day events are the filing and the initial employment assignment.
Pre-litigation transfer — Not present. The only transfer of record (1999-02-26) precedes the only known Incyte assertion activity (Invitrogen, 2001-11-21) by roughly 33 months, and there is no evidence this patent was in that suit.
Bankruptcy fire-sale — Not present. Incyte never filed Chapter 7/11; it restructured operationally (Nov 2001 management change, Sept 2001 restructuring, Feb 2004 Palo Alto shutdown) and remains a going concern. No Kodak/Nortel/Polaroid-style estate sale appears in the chain.
Privateering — Not present. The opposite pattern is documented: Incyte licensed its own array/genomics patents to Agilent (announced 2002-03-18) and cross-licensed with Affymetrix (2001-12-21) rather than farming enforcement out to an NPE. No operating company → NPE transfer is in the chain.
Defensive aggregator — Not present. The chain does not terminate at RPX, AST, LOT, Unified, or OIN. The inverse signal (neutralization) nonetheless arguably applies in economic effect: the patent lapsed for non-payment and is "Expired – Fee Related," so it is unassertable by anyone today.
Verdict
Insufficient data — the chain consists of only the original at-filing assignment (1999-02-26, inventors → Incyte Pharmaceuticals, Inc.), with no recorded post-issuance transfer that I could verify, and I was unable to retrieve reel/frame or correspondent fields from the Assignment Center. No NPE signal is present on the evidence available; the only corporate events are name changes within the same operating company (Incyte Pharmaceuticals → Incyte Genomics, 2000-07-07; → Incyte Corporation, 2003-03-15). Note the direction of the available evidence: the patent is "Expired – Fee Related," lapsed for non-payment of maintenance fees well before its 2019-02-26 nominal term, which is consistent with a non-asserted asset abandoned as Incyte exited genomics — but that is an inference from the legal-status field, not a reel/frame finding, and it should be confirmed against the maintenance-fee record in USPTO Patent Center. Verify at https://assignment.uspto.gov/patent/index.html#/patent/search/results?q=6410231 and https://patents.google.com/patent/US6410231/en.
Generated 9/27/2026, 10:32:34 PM
Prior art
Earlier patents, publications, and products that may anticipate or render the claims unpatentable.
I'll research the prior art cited for US 6,410,231. Let me run several targeted searches.
Let me get the face-of-patent references and the examiner-cited art.
I have the examiner-cited U.S. references. Let me verify the complete front-page reference list and gather details on each reference.
USPTO database lookup — confirmation of the target document
Searches against the specific number 6,410,231 (and no substitute) returned a single, consistent record. The front-page/issue data I confirmed:
| Field | Value |
|---|---|
| Patent | US 6,410,231 B1 — "SNP Detection" |
| Filed | Feb. 26, 1999, Appl. No. 09/259,898 |
| Granted | Jun. 25, 2002 |
| Assignee | Incyte Genomics, Inc., Palo Alto, CA |
| Inventors | Lyle Arnold; Thomas Theriault; Tod Bedilion |
| Int. Cl.⁷ | C12Q 1/68; C12P 19/34; C07H 21/04 (U.S. CL 435‑6) |
| Primary Examiner / Asst. | W. Gary Jones / Jehanne Souaya |
| Claims | 20 claims (per the USPTO issue gazette, Issue 1259‑4) |
Sources: the issued patent PDF (patentimages US6410231.pdf), the USPTO issue-gazette transcription (webapp1.dlib.indiana.edu/virtual_disk_library/…/us06410231-20020625.html), and the Justia face-page rendering (patents.justia.com/patent/6410231).
⚠️ Contradiction with a previously generated section — flag as required. The earlier "Patent summary" states the patent "carries claims 1–17." The official issue-gazette record reads "20 Claims," and it reproduces claim 1 with the "provide a first discrimination … provide a second discrimination" language. The authoritative issue data control: this patent has 20 claims, not 17. Any downstream analysis built on the "17 claims / two independents (1 and 16)" premise should be re-checked against the 20-claim set.
Prior art cited on the face of US 6,410,231
The examiner/applicant "References Cited" block comprises eight U.S. patents and one PCT publication (per the Justia face-page rendering; the same list is consistent with the granted PDF). These are the references the Office actually considered.
| # | Reference | Date (grant/pub) | Statutory basis vs. 2/26/1999 filing | Claims potentially affected |
|---|---|---|---|---|
| 1 | US 5,627,032 — Ulanovsky | May 6, 1997 | §102(a)/(b) | 2, 11 (degenerate set) |
| 2 | US 5,633,134 — Shuber | May 27, 1997 | §102(a)/(b) | 1, 6, 7, 15, 16 |
| 3 | US 5,700,637 — Southern | Dec. 23, 1997 | §102(a)/(b) | 1, 5, 14 |
| 4 | US 5,801,155 — Kutyavin et al. | Sep. 1, 1998 | §102(a)/(b) | 8, 9, 10 |
| 5 | US 5,830,645 — Pinkel et al. | Nov. 3, 1998 | §102(a)/(b) | 1(b), 6, 15 |
| 6 | US 5,976,798 — Parker et al. | Nov. 2, 1999 | §102(e) only (post-filing grant) | TBD — see caveats |
| 7 | US 6,017,696 — Heller | Jan. 25, 2000 | §102(e) only | 1, 5, 14 |
| 8 | US 6,051,379 — "Lescallet" et al. | Apr. 18, 2000 | §102(e) only | TBD — see caveats |
| 9 | WO 96/31622 | Oct. 1996 | §102(a)/(b) | TBD — see caveats |
Threshold point on §102(e): References 6–8 granted after the Feb. 26, 1999 filing date, so they cannot be §102(a)/(b) art. They can only be §102(e) art, and only if their effective U.S. filing dates pre-date the applicant's invention date. That determination requires the filing dates, which I have not verified (flagged below).
Per-reference detail
1. US 5,627,032 — Ulanovsky (granted May 6, 1997).
Directed to sequencing by hybridization (SBH) — determining nucleic acid sequence by hybridizing a target against a complete/degenerate set of short oligonucleotide probes (all possible N‑mers), typically in an arrayed or separate format. This is the single most relevant cited art for the degenerate-set limitations: dependent claims 2 and 11 ("assay probes comprise a degenerate set of all possible same-sized polynucleotides") find direct §102-type support here, since SBH by definition enumerates all same-length probes. It does not appear to disclose the SNP-allele-selective sandwich architecture or the two-stage discrimination of independent claim 1.
Confidence: strong as to claims 2/11; weak as to claim 1.
2. US 5,633,134 — Shuber (granted May 27, 1997).
A method of detecting a nucleotide change (point mutation) in nucleic acids. It is expressly cited in the '231 specification's background list of SNP-detection techniques. Potentially bears on the general "detect a SNP with a labeled probe" concept (claims 1, 6, 15) and on discrimination (claim 7), but discloses a solution-phase/amplification-based mutation detection, not the immobilized-capture array sandwich.
Confidence: moderate on the general concept; low on the claim-1 combination.
3. US 5,700,637 — Southern (granted Dec. 23, 1997).
Immobilizing polynucleotides on a solid support and analyzing target sequences by hybridization — the foundational array-hybridization disclosure (Oxford Gene Technology). Directly relevant to claim 1's "capture polynucleotides are immobilized and arrayed at corresponding discrete elements on a substrate" and to the high-density arraying limitations of claims 5 and 14.
Confidence: strong on the arraying/immobilization limitations; not a full anticipation of claim 1.
4. US 5,801,155 — Kutyavin et al. (granted Sep. 1, 1998).
Oligonucleotide probes conjugated to minor groove binders (MGBs) via linkers, to stabilize duplexes, raise Tm, and sharpen mismatch discrimination. The '231 specification cites this exact patent in its MGB discussion. This is the strongest §102 candidate for the MGB-dependent claims: claim 10 (MGB tethered to the SNP probe, capture polynucleotide, or auxiliary probe), claim 9 (SNP probe interacting with capture/auxiliary probe), and claim 8 (reagent normalizing melting temperatures — MGB conjugation equalizes Tm across probe sequences, a point the '231 specification itself concedes).
Confidence: highest of the cited set for claims 8–10; still does not disclose the full arrayed sandwich method of claim 1.
5. US 5,830,645 — Pinkel et al. (granted Nov. 3, 1998).
Comparative genomic hybridization (CGH) — labeled nucleic acids hybridized to target nucleic acids (chromosomes/arrays) and detected. Relevant to the label-and-detect steps (claim 1(b); claims 6, 15), but CGH addresses copy-number imbalance, not single-base allele discrimination.
Confidence: low–moderate.
6. US 5,976,798 — Parker et al. (granted Nov. 2, 1999).
Nucleic-acid hybridization/detection art. Because it granted after the '231 filing date, its §102(e) status depends entirely on its effective filing date. I have not verified its subject matter or filing date.
Confidence: unverified — must be checked before any §102(e) assertion.
7. US 6,017,696 — Heller (granted Jan. 25, 2000).
Nanogen's actively programmable electronic microarray devices — capture probes addressed/immobilized at discrete electrode sites, then hybridized and detected. Relevant to the "immobilized and arrayed at corresponding discrete elements on a substrate" limitation (claim 1) and high-density arraying (claims 5/14). §102(e) basis only.
Confidence: moderate on the immobilization/array limitation; not the SNP discrimination.
8. US 6,051,379 — "Lescallet" et al. (granted Apr. 18, 2000).
Subject matter not verified. §102(e) basis only. Note: the cited surname appears as "Lescallet," which may be an OCR/transcription variant; per my operating rules I have not auto-corrected it, and the identity of this reference should be confirmed against the granted PDF.
Confidence: unverified.
9. WO 96/31622 (published Oct. 1996).
A PCT publication — because October 1996 is more than one year before the Feb. 26, 1999 filing, it qualifies as prior art under both §102(a) and §102(b). I could not verify its subject matter or applicant; treat its §102 exposure as unverified pending retrieval of the document.
References cited in the description (background art, not on the face)
The specification separately cites a broader SNP-detection art set. These are relevant context but were not necessarily examiner-considered:
- Patents: Sapolsky et al. (1999) US 5,858,659; Shuber (1997) US 5,633,134; Dahlberg (1998) US 5,719,028; Mundy US 4,656,127; Kutyavin et al. (1998) US 5,801,155; and arraying patents US 5,807,522; 5,770,151; 5,861,242; 5,858,659; 5,856,174; 5,856,101; 5,837,832; 5,384,261.
- PCT applications: WO 98/30717; WO 97/10366; WO 98/44157; WO 98/20165; WO 95/12607; WO 98/30883; WO 97/31256; WO 98/12355; WO 98/14616; WO 91/02087; WO 92/15712.
- NPL: Lai et al., Genomics 1998; Gu et al., Hum Mutat 1998; Taillon‑Miller et al., Genome Res 1998; Weiss, Genome Res 1998; Zhao et al., Am J Hum Genet 1998; Chen et al., Genome Res 1998; Ross et al., Anal Chem 1997; Hauser et al., Plant J 1998; Landegren et al., Science 1988; Nickerson et al., PNAS 1990; Prezant et al., Hum Mutat 1992; Ugozzoli et al., GATA 1992; Nyrén et al., Anal Biochem 1993; Piner et al., Science Jan. 29, 1999; Lukhtanov et al., Bioconjugate Chem 1995.
Two of these (Sapolsky US 5,858,659, an array-based allele-discrimination reference; and the Piner Science dip‑pen nanolithography paper cited for arraying) are arguably more on-point to claim 1 than several face-of-patent references, and warrant review if a full validity landscape is needed.
Recommended artifacts for a complete §102 picture
- The granted PDF front page (patentimages.storage.googleapis.com/fc/49/32/a71848885cee1b/US6410231.pdf) to capture any foreign patent documents and "Other References" beyond those rendered by Justia.
- File-wrapper / Office actions via USPTO Patent Center for Appl. 09/259,898, to see the examiner's stated §102/§103 grounds and which claims each reference was actually applied against — this is the only way to convert "potentially anticipates" into the examiner's actual position.
- Filing dates for US 5,976,798; 6,017,696; and 6,051,379, to test §102(e) availability.
Caveats (explicit)
- "Potentially anticipates" is analytical, not the Office's holding. US 6,410,231 issued over all nine face-of-patent references; none was applied to invalidate the independent claims as granted. My mappings above are hypothetical §102 exposures by claim, and I have not seen the examiner's rejections.
- Independence requirement: Anticipation under §102 requires every limitation of a claim in a single reference. On the face of it, none of these references individually appears to disclose the full claim-1 combination (arrayed capture polynucleotide → first discrimination → allele-selective SNP probe → second discrimination → element-localized detection). The strongest single-reference exposures are confined to dependent claims: US 5,627,032 (claims 2/11), US 5,700,637 (claims 5/14 arraying), US 5,801,155 (claims 8–10 MGB).
- Unverified items: US 5,976,798 (Parker), US 6,051,379 ("Lescallet"), and WO 96/31622 — I did not confirm subject matter, applicant, or filing dates. Do not treat these as characterized.
- Post-filing grants: US 5,976,798; 6,017,696; and 6,051,379 can only be §102(e) art; their usability turns on effective filing dates I have not verified.
- Forward citations are not prior art. The 36 documents listed under Google Patents' "Cited By" (e.g., US 2003/0073122; US 6,844,154) cite this patent and therefore post-date it; they are not §102 art against the '231 and should not be listed as such.
- Family-member nuance: WO 00/50869 A2 / US 2003/0059813 A1 are the '231's own family, and WO 00/50869 was used as "X" art by later examiners against other applications (claims 1–9, 12, 20–22, 27, 29, 30 of the WO 2005121359 applicant) — relevant context, but not prior art against the '231 itself.
Generated 9/27/2026, 10:32:48 PM
Obviousness
Combinations of prior art that suggest the claimed invention would have been obvious under 35 U.S.C. § 103.
I'll ground my obviousness analysis in the actual prior-art references named in this patent's Background section and specification. Let me verify their disclosures.
Strong confirmations obtained. Let me verify the remaining named references in the Background and the array-immobilization art.
Obviousness Analysis — U.S. Patent 6,410,231 ("SNP detection") under 35 U.S.C. § 103
1. Scope, law, and what I used as the prior-art corpus
Governing law. The application was filed 1999‑02‑26, so pre‑AIA § 102/§ 103 applies (AIA first‑inventor‑to‑file governs applications filed on/after 2013‑03‑16). The controlling framework is Graham v. John Deere, 383 U.S. 1 (1966) (scope/content of art; differences; level of ordinary skill; objective indicia), as refined by KSR Int'l v. Teleflex, 550 U.S. 398 (2007), and In re Keller, 642 F.2d 413 (CCPA 1981) (test the combined teachings, not each reference in isolation).
Prior-art corpus. Per your instruction I used the prior-art material on the US 6,410,231 page — i.e., the "Prior art date 1999‑02‑26" and the references the patent itself names in its Background and specification (the page's "Definitions"/concept extraction merely lists those same documents). Two points make this corpus unusually strong:
- The '231 Background expressly cites US 5,858,659 (Sapolsky), US 5,633,134 (Shuber), US 5,719,028 (Dahlberg), US 5,801,155 (Kutyavin), and WO 98/30883 (Cronin) as known SNP-interrogation art. Under In re Fritch / MPEP 2129, an applicant's citation of art in the specification is an admission as to what the art discloses.
- The '231 specification's biological-sample paragraph — the Lench mouthwash cite, Burk & Spitzer, Gasparini, Higuchi, Bianchi, "embryonic cells obtained from biopsied embryos" sequence — is substantially identical text, in the same order, to the corresponding passage of Shuber's US 5,633,134 (confirmed against the Google Patents disclosure of US 5,633,134 and its DE 695 31 831 T2 family member). Same for the ASO-pool optimization language ("approximately the same length," "0.03 pmol," "concentration was doubled," "cystic fibrosis transmembrane regulator gene"). That is textual evidence that the '231 drafter regarded Shuber as describing the same invention space.
Claim set analyzed. Claims 1–17 as retrieved in the prior section: independent claims 1 and 16; dependents 2–15, 17. I carry forward the earlier caveat — the authoritative text supplied to me omits the claims, and retrieved claim 17 anomalously reads "The method of claim 10…." I do not auto-correct it; claim 17's dependency is unverified, and if claim 17 is a dependent of claim 16, my analysis of the MGB/universal-set combination applies to it directly.
2. The prior art, with verified disclosures
| Ref | Status vs. 1999‑02‑26 | What I verified it discloses |
|---|---|---|
| US 5,633,134 (Shuber), "Method for simultaneously detecting multiple mutations in a DNA sample," issued 1997‑05‑27 (Google Patents) | § 102(b) — statutory bar (>1 yr before filing) | Multiplex mutation detection by "hybridizing the sample with multiple allele specific oligonucleotide probes of approximately the same length under stringent conditions in the presence of an appropriate concentration of an agent that eliminates disparities in melting temperature and detecting hybridization." Preferred agent = quaternary ammonium salt (TMAC). ASOs labeled with radioisotopes or fluorochromes; ASO pools of approximately the same length; empirical pool-concentration optimization; the same genomic‑DNA source list the '231 copies. |
| US 5,858,659 (Sapolsky, Affymetrix), "Polymorphism detection," issued 1999‑01‑12 (Google Patents) | § 102(a) | Arrays of oligonucleotide probes for detecting a polymorphism; detection blocks with first/second probes complementary to two variants and third/fourth probes "including all possible monosubstitutions" within n = 0–5 bases; methods of screening genomic material for polymorphisms; claim 1 recites comparing first/second hybridization intensities against an average ± 2 SD and calling the perfect match; claim 4 recites the ratio thresholds (>2 = variant 1; <0.5 = variant 2; 0.5–2.0 = both = heterozygote); 100–3000 detection blocks. |
| WO 98/30883 (Cronin et al., Affymetrix), publ. 1998‑07‑16 (PDF); US counterpart US 6,468,744 | Printed publication / § 102(e) | Tiling arrays of four probe sets differing at an interrogation position; relative specific binding of the four corresponding probes assigns the target nucleotide; "call ratio" of 1.2; express teaching that a chip can "simultaneously detect and quantify proportions of multiple target sequences," including "diagnosis of patients who are heterozygous"; quantitative calibration with seeded mixtures. |
| US 5,801,155 (Kutyavin, Lukhtanov, Gamper, Meyer, Epoch), "Covalently linked oligonucleotide minor groove binder conjugates," issued 1998‑09‑01 (Espacenet; US 6,084,102 PDF) and its EP 0819133 family (EP0819133B1 PDF) | § 102(a) (US '155); EP family published 1998 | Minor groove binder covalently tethered to an oligonucleotide via a linker of ≤ 15 atoms; the exemplified MGB is the CDPI₃ trimer (1,2‑dihydro‑(3H)‑pyrrolo[3,2‑e]indole‑7‑carboxylate). The family disclosure states the conjugates "form unusually stable hybrids," allow 8‑mer probes, and that "MGB conjugation also increases the discriminatory power of short oligonucleotides, providing enhanced detection of nucleotide sequence mismatches," expressly facilitating "detection of single-nucleotide polymorphisms." |
| US 5,719,028 (Dahlberg, Third Wave), "Cleavase fragment length polymorphism," issued 1998‑02‑17 (Google Patents) | § 102(b) | 5′‑nuclease structure‑specific cleavage to "screen for known and unknown mutations, including single base changes"; extensive survey of signal-amplification and mutation-scanning alternatives. |
| Array-fabrication art cited in the '231 specification itself: US 5,807,522; 5,770,151; 5,861,242; 5,858,659; 5,856,174; 5,856,101; 5,837,832; 5,384,261; Piner et al., Science (Jan. 29, 1999) 661–663 | § 102(a)/(b) / admissions | The '231 specification recites contact deposition, photolithography, flow‑path and dip‑pen nanolithography as "known in the art" for "arraying polynucleotides at discrete elements of substrates." This is an admission that high‑density arraying of polynucleotides onto a substrate was routine. |
I did not independently verify the disclosures of WO 98/20165 (Lander), WO 95/12607 (Goelet), WO 98/44157 (Murphy), WO 98/30717 (Murigneux), US 5,719,028's claim scope, or the array-fabrication patents themselves in this session; I rely on them only as background/§ 102(e) candidates. Flagged at § 11.
3. Level of ordinary skill
A POSITA in February 1999 would be a Ph.D. (or M.S. with several years' experience) in molecular biology/biochemistry with working familiarity in (i) allele‑specific oligonucleotide hybridization and its stringency/Tm problems, (ii) microarray fabrication and confocal fluorescence readout of hybridized arrays, and (iii) nucleic acid probe conjugation chemistry. The knowledge required to combine these references is ordinary — the '231 specification itself describes the entire process as conventional, citing Schena 1995, Shalon 1996 and the arraying patents as the operative methods.
4. Ground 1 — Claim 1 is obvious over Shuber '134 in view of Sapolsky '659 (and Cronin WO 98/30883)
Claim chart (independent claim 1)
| Claim 1 limitation | Disclosure in the combination |
|---|---|
| (a) combining target polynucleotides, capture polynucleotides, and SNP probes | Shuber '134: sample DNA + pooled allele‑specific probes in one hybridization reaction. Sapolsky '659: target hybridized to an array of probes. |
| each target comprising a different capture region and a different SNP region | Shuber '134: "The polymorphic site of each probe is generally flanked on both sides by regions common to the different alleles" — i.e., a captured/conserved region distinct from the polymorphic region. |
| capture polynucleotides immobilized and arrayed at corresponding discrete elements on a substrate, each hybridizing a corresponding different capture region | Sapolsky '659: "arrays of oligonucleotide probes," with detection blocks at "separate" array positions; Cronin WO 98/30883: four probe sets arranged at array columns. Arraying onto glass/silicon/nylon at ≥100 elements/cm² was, per the '231 spec's own citations, known. |
| each SNP probe complementary to a corresponding SNP region | Shuber '134: allele‑specific oligos "designed to identify allele specific mutations"; pairs differing by one base, labeled differently. |
| each target immobilized by hybridizing to a capture polynucleotide at a corresponding discrete element | The '231's own "sandwich" architecture = immobilized capture + hybridized target. Shuber '134/i> teaches target may be bound to a solid support and probed with a pool of ASOs. |
| relative affinity of each SNP probe … sufficient to provide selective hybridization | Shuber '134 verbatim: "an appropriate concentration of an agent that eliminates disparities in the melting temperature of the ASOs," TMAC preferred, plus stringent hybridization/washes and same‑length ASOs. |
| (b) detecting the SNP probe on the substrate; presence at an element ⇒ presence of the SNP | Shuber '134: labeled ASOs, detection of hybridization. Sapolsky '659: fluorescent target/probe read-out with a 2‑SD perfect‑match criterion. |
Differences and why they are obvious
The only material difference from Shuber '134 is spatial: partitioning the individual hybridizations into addressable array elements instead of one pool in a single tube. That difference is squarely met by Sapolsky '659, which applies the same allele‑specific‑hybridization chemistry in an addressable array (Sapolsky claim 1: "identifying said first or second hybridization intensity as a perfect hybridization match when said first or second hybridization intensity is greater than two standard deviations of said average …") and by Cronin WO 98/30883's tiling arrays.
Motivation to combine (KSR factors)
- Same field of endeavor / reasonably pertinent. Both are nucleic‑acid‑based polymorphism/mutation scoring for the identical stated purposes (genetic linkage, disease diagnosis). KSR: combining references "addressing the same problem" is obvious.
- Shuber identifies the very deficiency the array cures. Shuber '134 states ASOs can be pooled (>50 per pool) but that the method is "limited by the requirement to perform subsequent multiple individual hybridizations to identify the relevant ASO from the pool." An array that returns the identity of each probe from its address eliminates that step. The prior art itself supplies the "reason to modify."
- Explicit prior-art design incentive for high density/parallelism. Sapolsky '659: "arrays and methods useful in screening large numbers of polymorphic markers in a genome"; Cronin WO 98/30883: chip‑scale analysis of pre‑characterized mutations and heterozygote calling.
- Predictable result. Discretizing a known hybridization reaction onto a substrate with known capture/probe chemistry is a rearrangement of known elements with predictable results (In re Kahr, In re Rose line of reasoning) — nothing in the citations suggests a loss of performance.
- Enabling arraying was admitted conventional. The '231 specification itself lists the arraying patents and Piner 1999 as known.
5. Ground 2 — Claims 7, 8, 16 (two‑probe‑pair / quantitative discrimination) are obvious over Shuber '134 + Sapolsky '659, further in view of Kutyavin '155
Claim 16 requires (i) an assay probe pair — a first probe perfectly complementary to the SNP region and a second probe with a single‑base mismatch; (ii) "discriminating conditions" comprising a Tm‑normalizing reagent and/or SNP‑probe interaction with the capture/auxiliary probe; and (iii) a ≥ 2‑fold increase in the matched:mismatched hybridization ratio.
- Probe pairs, allele‑flanking common regions, one‑base difference, differential labels → Shuber '134 (labeled allele‑specific probe pairs).
- Tm‑normalizing reagent — the literal language of claim 8/16: "a reagent which normalizes the melting temperatures of the assay probes" is Shuber '134's "agent that eliminates disparities in the melting temperature," expressly tetramethylammonium chloride/fluoride and tetraethylammonium salts — precisely the reagents the '231 specification recites.
- Ratio‑based calling and the ~2‑fold threshold → Sapolsky '659 claim 4 ("when said ratio is greater than 2 … said first variant is present … when said ratio is less than 0.5 … second variant … between about 0.5 and 2.0 … both variants present"); Cronin WO 98/30883 (call ratio 1.2; relative specific binding of four probes; heterozygote detection). Choosing a ≥ 2‑fold discrimination threshold is routine optimization of a disclosed parameter (In re Aller: a result‑effective amount obtained by routine experimentation is obvious).
- "Second discrimination" arising from capture‑polynucleotide/auxiliary‑probe interaction → this is the MGB/stacking‑cooperativity concept taught by Kutyavin '155 (see Ground 3) and the known base‑stacking cooperativity of adjacently hybridized probes.
Result: the claim‑16 combination is a re‑arrangement of Shuber's probe pair + Shuber's TMAC + Sapolsky's ratio threshold + Kutyavin's MGB, in a field where all four references address the same problem (reliable discrimination of a one‑base difference in a multiplexed format).
6. Ground 3 — Claim 10 (MGB tether) and claims 2/11/17 (degenerate, universal detector set) are obvious
Claim 10 — MGB tethered to the SNP probe, capture, or auxiliary probe
- Kutyavin '155 teaches, as a composition, an MGB covalently attached to an oligonucleotide through a linker of ≤ 15 atoms, with the MGB being CDPI₃ or equivalent — the identical chemistry the '231 Examples 3–4 use ("CDPI₃ was conjugated to the 3′ end of the oligonucleotide"; "3′‑(MGB)‑NNXNN‑(Label)‑5′").
- Critically, the EP 0819133 family abstract states the MGB conjugate "increases the discriminatory power of short oligonucleotides, providing enhanced detection of nucleotide sequence mismatches" and that the conjugates "facilitate … detection of single‑nucleotide polymorphisms." That is an express, art‑supplied motivation to attach an MGB to a short allele‑specific SNP probe.
- The '231 specification itself concedes the MGB's Tm‑equalization property: "the minor groove binders enable melting temperature equalization between different probes sequences." That statement is an admission of known MGB function, and it is the very function recited in claims 8/16.
- Therefore claim 10 is obvious over Shuber '134 or Sapolsky '659 in view of Kutyavin '155, with the motivation supplied by Kutyavin's own SNP/mismatch statement plus Shuber's express concern with Tm disparities across a multiplexed probe pool.
Claims 2, 11, 17 — degenerate set of "all possible same‑sized polynucleotides" with position‑specific labels
- Sapolsky '659 already claims arrays comprising probe groups "including all possible monosubstitutions of positions in the sequence that are within n bases of a base corresponding to the polymorphism, where n is from 0 to 5" — i.e., an exhaustive degenerate set of same‑length probes spanning the interrogation position, with the perfect match read out.
- Cronin WO 98/30883 tiles four probe sets differing only at the interrogation position, and computes relative binding across the four.
- Combining those with routine labeling of each base identity with a distinguishable fluorophore (Cy2/Cy3/Cy5/Cy7, per the '231 Tables 1–2 and Shuber's label list) yields the "universal detector set." Choosing a five‑mer (5 nt, = 4⁵ = 1024 members) instead of a longer degenerate pool is routine selection of a known working range; Kutyavin '155 teaches MGB conjugates "as short as 8‑mers," providing the reason a short degenerate probe could be made allele‑discriminating.
The declaratory statement in the '231 that this format "provides in essence, a universal detector set" is a statement of intended use/result, not a structural distinction from the Sapolsky/Cronin tiling arrays.
7. Dependent claims 3–6, 12–15
| Claim | Obviousness basis |
|---|---|
| 3 / 12 (sample = fragmented genomic DNA) | Shuber '134 names genomic DNA from blood leukocytes, buccal cells, cervicovaginal cells, urine, hair roots, amniotic fluid, cord blood, CVS, maternal blood, biopsied embryos — the identical list in the '231 specification. |
| 4 / 13 (capture polynucleotides = segregated, arrayed cDNA library) | Routine: arrayed cDNA libraries (Schena 1995, Science 270:467–470; Shalon 1996, Genome Res. 6:639–645 — both cited in the '231) were standard; using a cDNA array as a complexity‑reduction capture was an obvious use of an admitted known tool. |
| 5 / 14 (high‑density arraying, ≥100/cm²) | Trivially met by the photolithographic arrays of the art the '231 cites (e.g., US 5,837,832; US 5,861,242; US 5,858,659 detection blocks "100 to 3000"). |
| 6 / 15 (SNP probe comprises a label) | Shuber '134 non‑isotopic/isotopic labeling; Sapolsky claim 1 (fluorescent label). |
| 7 (enhanced discrimination vs. other SNP regions) | Shuber's stringent conditions + TMAC; Kutyavin's enhanced mismatch discrimination. |
| 9 (interaction with capture/auxiliary probe) | Base‑stacking/cooperativity of adjacently hybridized probes; Kutyavin '155 (MGB in the duplex minor groove). |
8. Motivation‑to‑combine synthesis (the KSR "articulated reasoning")
A POSITA in February 1999, knowing (i) Shuber's multiplex ASO hybridization with Tm‑normalizing quaternary ammonium salts, (ii) Sapolsky's and Cronin's demonstration that the identical allele‑specific hybridization could be read out at addressable array elements with quantitative PM/MM ratios, and (iii) Kutyavin's MGB‑conjugated short probes with enhanced mismatch discrimination, would have had every reason to:
- Replace Shuber's "pool then deconvolute by serial individual hybridizations" workflow with an addressable array, because the array's address is the probe identity — Shuber itself names the deconvolution step as the method's limitation.
- Keep the Tm‑normalizing reagent, because Shuber teaches it is needed whenever probes of differing sequence are pooled/arrayed and hybridized in one reaction, and because MGB conjugation (Kutyavin) provides the same equalization.
- Use short, MGB‑tethered allele‑specific probes, because Kutyavin expressly teaches that MGB conjugation increases mismatch discrimination and enables shorter probes — which directly serves the '231's stated goal of a ≥ 2‑fold (indeed ≥ 10‑fold) match:mismatch ratio.
- Read genotypes from quantitative ratios, because Sapolsky's claim 4 and Cronin's call‑ratio teaching establish ratio thresholds (>2 / <0.5 / 0.5–2.0) as the accepted way to call homozygous vs. heterozygous.
Each step is a combination of known elements for their known functions, with a reasonable expectation of success, in a predictable art — the KSR standard.
9. Where the obviousness case is weaker (honest counter‑analysis)
I would be doing you a disservice not to flag these:
- The specific architecture of claim 1 is not literally in any single reference. Shuber '134 is a tube‑based pool assay; Sapolsky's array elements are interrogation probes, not non‑allele‑specific capture probes with solution‑phase allele‑specific detectors. A patentee's strongest response is that the "capture the target at a non‑discriminating address, then genotype with a separate labeled probe" architecture is a distinct, non‑suggested rearrangement — a hindsight attack. Expect the patentee to argue In re Kotzab/Metalcraft‑type "the references teach away from separating capture from interrogation."
- The '231 Example 3 data (≥10‑fold Cy3:Cy5 improvement with 11‑mer MGB probes vs. the 15‑mers of Example 1) is the patent's best objective‑indicia hook. But it is substantially undermined by Kutyavin '155, whose family disclosure predicts exactly that outcome ("enhanced detection of nucleotide sequence mismatches by short oligonucleotides"). Under In re Merck / In re Geisler, an improvement that is forecast by the prior art is not a strong unexpected‑results showing.
- No secondary‑consideration record exists. The patent expired for failure to pay maintenance fees (anticipated expiration 2019‑02‑26) and, as established in the prior sections, I found no litigation, no evidence of licensing, no copying, no industry praise attributable to it. That cuts against patentee.
- The genuinely inventive‑looking subject matter is in the Examples, not the claims. Modification A (2′‑O‑methyl ribonucleotides in the capture terminus to block MGB binding), Modification B (blunt‑end design), and Example 5's chimeric 2′‑O‑methyl / 2′‑deoxy capture with a tethered MGB appear, on the claim set I have, to be unclaimed. If a district court finds the printed claims narrower than the specification (e.g., construing "relative affinity … sufficient to provide selective hybridization" as a result‑oriented limitation requiring the MGB cooperativity), invalidity risk shifts, but a non‑limiting construction favors the obviousness case.
- Anticipation is unlikely to be the right theory. Because no single reference appears to disclose "capture polynucleotides arrayed at discrete elements" together with separately‑supplied allele‑specific SNP probes, § 103, not § 102, is the correct attack. If you need a § 102 theory, Sapolsky '659 or Cronin WO 98/30883 may anticipate the universal‑detector dependent claims, but not claim 1.
10. Recommended grounds, ranked by strength
| Rank | Ground | Claims | Confidence |
|---|---|---|---|
| 1 | US 5,633,134 (Shuber) + US 5,858,659 (Sapolsky) — optionally + WO 98/30883 (Cronin) | 1–9, 11–16 | High for the method steps; moderate because of the capture‑vs‑interrogation architecture point |
| 2 | Shuber '134 + Sapolsky '659 + US 5,801,155 (Kutyavin) / EP 0819133 | 10, 16, 17 | High — Kutyavin supplies both the structure (tether) and the express SNP/mismatch motivation |
| 3 | Shuber '134 (TMAC) alone or + Sapolsky | 8 | Very high — near‑verbatim correspondence |
| 4 | Sapolsky '659 + Cronin WO 98/30883 + Shuber '134 | 2, 11, 17 (degenerate "universal" set) | High — Sapolsky's "all possible monosubstitutions" + Cronin's four‑set tiling |
| 5 | Shuber '134 + the admitted arraying art (US 5,807,522; 5,837,832; 5,861,242; 5,384,261; Piner 1999) | 5, 14 (high density) | Very high — applicant's own admission |
| 6 | US 5,719,028 (Dahlberg) | Background only | Low relevance — teaches 5′‑nuclease scanning, not the claimed sandwich read‑out |
11. Caveats and verification gaps
- Claim text. The authoritative full text supplied to me omits the claims. My limitation‑by‑limitation chart for claim 1 and my reading of claims 8, 10, 16 and 17 rest on the FreePatentsOnline rendering summarized in the prior sections. Before filing anything, pull the printed claims from USPTO Patent Public Search or the patent PDF at patents.google.com/patent/US6410231/en. In particular, claim 17's dependency ("The method of claim 10…") is unverified and I have not auto‑corrected it.
- Unverified references. I did not retrieve the text of WO 98/20165 (Lander), WO 95/12607 (Goelet), WO 98/44157 (Murphy), WO 98/30717 (Murigneux), WO 97/10366 (Shuber), WO 97/31256 (Barany), or the array‑fabrication patents (US 5,807,522; 5,770,151; 5,861,242; 5,856,174; 5,856,101; 5,837,832; 5,384,261) in this session. I rely on them only insofar as the '231 specification cites them as known, or as § 102(e) candidates.
- Publication dates. I verified issue dates for US 5,633,134 (1997‑05‑27), US 5,858,659 (1999‑01‑12), US 5,719,028 (1998‑02‑17) and US 5,801,155 (1998‑09‑01) from the retrieved records. The EP 0819133 publication date is inferred from the 1995/1996 priority and 1998 family date; confirm the A1 publication date before relying on EP 0819133 as § 102(b) art. The US '155 (1998‑09‑01) is § 102(a) art regardless.
- "Sandwich hybridization" as general knowledge. The proposition that immobilized‑capture + labeled‑detector "sandwich" hybridization on a solid support was routine before 1999 (e.g., Ranki et al., Gene 21:77–85 (1983)) comes from my training data and was not verified by search in this session. If you intend to assert this as a formal reference, verify it first; otherwise rest Ground 1 on Shuber '134 + Sapolsky '659 + Cronin.
- Pre‑AIA vs. AIA. My analysis uses pre‑AIA § 103. If any claim were ever examined or challenged under AIA standards (it cannot be, given the 1999 filing), the KSR‑based reasoning here would only be easier to sustain.
- No litigation exists to test these grounds. Per the prior sections, US 6,410,231 was never asserted or challenged and lapsed in 2019 for non‑payment. This is therefore a hypothetical validity analysis; no inter partes record (e.g., a PTAB IPR) exists to compare against.
Bottom line: Claims 1–17 of US 6,410,231 present a strong prima facie § 103 case built almost entirely on references the applicant itself cited — Shuber US 5,633,134 (multiplex labeled allele‑specific probes of equal length + Tm‑normalizing quaternary ammonium salt), Sapolsky US 5,858,659 and Cronin WO 98/30883 (addressable array read‑out with quantitative PM/MM ratio calling, including a >2‑fold threshold and heterozygote detection), and Kutyavin US 5,801,155 / EP 0819133 (MGB‑tethered short probes with expressly stated enhanced SNP/mismatch discrimination). The applicant's only meaningful rebuttal is the argument that no reference suggested decoupling the capture function from the interrogation function on an array; the specification's Example 3 "10‑fold improvement" is largely if not entirely foreshadowed by Kutyavin's own statement that MGB conjugation increases the discriminatory power of short oligonucleotides.
Generated 9/27/2026, 10:33:27 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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