US 6291170

I'll search for authoritative information on this patent number, including any 2026 litigation activity.

Let me search further for litigation and docket information, and confirm the assignee details.

Let me run a couple more targeted searches to check for any litigation or PTAB proceedings.

US 6,291,170 B1 — Summary

Caveat on scope of search: I was able to retrieve the patent document itself (authoritative text supplied, corroborated by Google Patents and FreePatentsOnline). I was not able to verify any active USPTO proceeding or any 2026 CAFC docket involving this patent. Targeted searches for litigation/CAFC activity returned no matching results (one query returned an empty result set). The Google Patents family page does carry a "Family has litigation / First worldwide family litigation filed" flag pointing to a Darts‑IP family record, but I could not resolve that to a specific case from the available results. Treat the litigation/docket point as unconfirmed.

Bibliographic data

Continuity (per the "Related Applications" paragraph): this patent is a continuation of Ser. No. 08/922,965 (now US 5,891,636), itself a continuation of 08/636,748 (now US 5,716,785), a continuation of 07/957,647 (now US 5,545,522), a continuation of 07/411,370 filed 1989-09-22 (abandoned). A later continuation, application 09/713,545, issued as US 7,049,102 B1 ("Multi-gene expression profile").

Abstract (as printed)

"This invention relates to the use of promoters for ribonucleic acid amplification and other genetic manipulations. Processes are provided wherein complementary deoxyribonucleic acid (cDNA) is synthesized from a ribonucleic acid (RNA) sequence using a complementary primer linked to an RNA polymerase promoter region complement and then anti-sense RNA (aRNA) is transcribed from the cDNA by introducing an RNA polymerase capable of binding to the promoter region. Additional processes using the resulting aRNA are also described."

Note the mismatch, which is real and worth flagging: the abstract and the bulk of the specification describe amplification methods (the "aRNA"/Eberwine–Van Gelder subject matter), whereas the granted claims are drafted to a product/assembly framed as an "expression profile."

Independent claims in plain language

Claim 1 — The "profile as an assembly" claim. A multi-gene expression profile of a sample made up of two things: (a) a hybridizing target, and (b) a hybridizing probe. The probe is a collection of amplified specific nucleic acid messages that were amplified in vitro, simultaneously, using an RNA polymerase plus a single primer linked to an RNA polymerase promoter. Each amplified message's relative abundance must qualitatively reflect the relative representation of specific messages in the original sample. The collection hybridizes to the target to form the multi-gene expression profile.

Plain language: it claims, in effect, the hybridization pairing itself — an amplified, promoter/single-primer-derived message population hybridized to a target, where the population's composition is claimed to track the sample's message abundances (qualitatively, not quantitatively).

Claim 4 — The "single cell" version. Same concept but the profile is "of a single cell": a collection of amplified specific nucleic acid messages amplified in vitro simultaneously with an RNA polymerase and a single primer linked to an RNA polymerase promoter, each message's relative abundance qualitatively reflecting the abundance of that message in the sample; plus a hybridizing target; the collection hybridizes to the target to form the profile. Notably, claim 4 recites the "single cell" in the preamble only, and the "sample" in the body is not expressly tied back to the single cell — a potential indefiniteness/antecedent point.

Dependent claims:

• Claim 2 — amplified messages are aRNA (anti-sense RNA).
• Claim 3 — amplified messages are cDNA.
• Claim 5 — "The multi-gene expression profile of claim 1, wherein the single cell is a neural cell." This is internally inconsistent as printed: claim 1 never recites a single cell, so "the single cell" in claim 5 lacks antecedent basis; it appears intended to depend from claim 4. I am reporting the text literally rather than correcting it.
• Claim 6 — depends from claim 5; the relative level of representation varies as a function of arousal state, behavior, drug treatment or development.

Points of uncertainty / things I could not confirm

1. No verified 2026 CAFC docket. I found no Federal Circuit appeal or USPTO (IPR/PGR/reissue) proceeding for US 6,291,170. Given the patent expired 2009-09-23, an infringement appeal in 2026 would be unusual, though it could theoretically surface in a collateral or declaratory posture.
2. Litigation flag unresolved. Google Patents marks the family as having litigation via a Darts‑IP link; the specific case(s), parties, and forum are not shown in the retrieved text, and my searches did not surface them.
3. Assignee naming varies between sources ("Leland Stanford Junior University" vs. "Board of Trustees of Leland Stanford University").
4. The two independent claims are product-by-assembly claims ("a hybridizing target; and a hybridizing probe …") rather than method claims — their validity/scope would turn on how the "qualitatively reflects" limitation is construed, which no retrieved source addresses.

If you want, I can attempt a further pass specifically on the Darts‑IP family ID 23628663 and the sibling patents (5,545,522 / 5,716,785 / 5,891,636 / 7,049,102) to pin down the litigation history.

I'll research litigation involving US patent 6,291,170. Let me run several targeted searches.

Let me try more specific queries against litigation databases.

Litigation Search — U.S. Patent No. 6,291,170

Summary answer

I could not verify, by name and case number, any specific federal court or ITC action asserting or challenging U.S. Patent No. 6,291,170 ("Multi-genes expression profile"). My searches did not return any docket, complaint, PTAB proceeding, or CAFC appeal that names this patent. However, I did find a litigation flag on the patent's own family record, which indicates that some litigation exists somewhere in this patent family. I cannot responsibly convert that flag into a case citation without the underlying docket. Details and limits below.

What I verified about the patent itself (grounding)

From the Google Patents record for US 6,291,170 B1 (source: https://patents.google.com/patent/US6291170/en) and FreePatentsOnline (https://FreePatentsOnline.com/6291170.html):

The one litigation signal I found — and its limits

The Google Patents page carries an event entry reading "Family has litigation — First worldwide family litigation filed," hyperlinked to Darts-ip (family ID 23628663, https://patents.darts-ip.com/?family=23628663). The same page also links USPTO PatentCenter, Assignment, and Espacenet records.

What this does and does not tell us:

• It tells us at least one litigation proceeding has been docketed involving a member of this patent family (a Darts-ip "first worldwide family litigation filed" event).
• It does not tell us the plaintiff, defendant, court, case number, or outcome — and, critically, it does not establish that the asserted (or challenged) patent was 6,291,170 rather than a sibling/ancestor (e.g., 5,545,522; 5,716,785; 5,891,636; 7,049,102). The flag is family-level, not patent-level.
• I therefore cannot list a case for 6,291,170 without attributing to it litigation that may name a different family member. I am declining to do that.

Searches performed and results

Important non-match to flag: the result Board of Trustees of Leland Stanford Junior University v. Roche Molecular Systems, Inc., No. 08-1509 (Fed. Cir. Sept. 30, 2009) concerns Stanford's HIV-treatment monitoring patents (inventor Mark Holodniy) and an ownership/standing dispute — not US 6,291,170. It should not be cited as litigation over this patent.

Why "no plaintiff/defendant/case number" is the correct present answer

The Google Patents record shows no "Cited By" or "Family" litigation entries naming a court or party for 6,291,170 itself, and the Darts-ip-linked flag is the only adversarial-proceeding indicator present. Because the patent expired 2009-09-23, any asserted infringement action would necessarily have been filed before that date (subject to the 35 U.S.C. § 286 six-year damages look-back), which further narrows the window I would search in paid dockets. Searching free sources alone did not surface a docket.

Recommended next steps to close the gap (would require sources I could not reach)

1. Darts-ip family ID 23628663 — the exact record Google Patents points to; this should name the case(s), parties, and forum.
2. USPTO PatentCenter / Assignment for 09/286,533 — check for recorded licenses or assignments that often accompany enforcement campaigns.
3. PACER / CourtListener (RECAP) — full-text docket search restricted to "6,291,170" (not the family), and to "6291170."
4. CAFC docket search for appeals naming Leland Stanford Junior University and this patent.
5. PTAB (AIA) search for IPR/PGR/CBM/dissemination of 6,291,170 — the patent expired in 2009, so AIA trials (post-2012) are unlikely, but pre-AIA inter partes reexamination requests should be checked.
6. Unified Patents portal litigation case list (https://portal.unifiedpatents.com/litigation/caselist) and their patent page for US-6291170-B1, which I was unable to load within this session.

Bottom line

Based strictly on what I could verify: no specific litigation naming US 6,291,170 can be reported — I have no plaintiff, defendant, jurisdiction, case number, filing date, or outcome to give you, and I will not invent them. The defensible finding is that the family (Darts-ip ID 23628663) shows a "first worldwide family litigation filed" event, which should be verified against Darts-ip or PACER before any assertion that 6,291,170 itself was litigated.

I'll start by verifying the canonical representation and then probe for any proceedings the ODP may not have indexed.

Let me run a few more targeted checks before concluding.

Proceedings overview

Total AIA trial proceedings on file for US 6,291,170: 0. The canonical structured block ("PTAB proceedings on file") states that the USPTO Open Data Portal returns no AIA trial proceedings for this patent, and my independent web checks corroborate that — I found no IPR, PGR, or CBM naming the '170 patent or any of its four family members (US 5,545,522; US 5,716,785; US 5,891,636; US 7,049,102). Breakdown by status is therefore: active 0 / claims invalidated 0 / claims sustained 0 / settled 0 / institution denied 0.

The bottom line for a defendant is not "the patent has survived two IPRs and is hardened." It is closer to the opposite: the claims are untested at the PTAB and can never be tested there again, because the patent expired on 2009-09-23 — roughly three years before the AIA's post-grant provisions (IPR/CBM/PGR, effective 2012-09-16) even existed. There is no IPR record to mine for cancellation, but there is also no live enforcement tail: the statutory term ran out nearly 17 years ago. Any demand letter citing the '170 patent today is asserting an expired patent.

Caveat on one data point: the Google Patents record shows a "Family has litigation" indicator with a first-worldwide-family-litigation entry (Darts-IP family 23628663, https://patents.darts-ip.com/?family=23628663). That is a litigation flag, not a PTAB flag. I could not verify the parties, venue, or dates within my search budget, and I will not guess at them. It is flagged as a lead only.

Proceedings overview — detail

No proceedings to enumerate. For completeness, here is the negative result and the surrounding record:

No AIA trial proceeding identified — USPTO ODP / PTAB E2E / web search

• Type: N/A (no IPR, PGR, or CBM on file)
• Filed: N/A
• Status: No proceeding. Patent legal status is "Expired - Lifetime," adjusted expiration 2009-09-23 (per the structured block and the Google Patents record).
• Judge panel: N/A
• Petition grounds: N/A
• Institution decision: N/A
• Final Written Decision: None issued
• Settlement / termination: N/A
• Appeal: No FWD, so no CAFC appeal of one
• Defensive value: The absence of IPR art is not a "hardened patent" signal here — it is a timing artifact. The '170 patent issued 2001-09-18 and expired 2009-09-23; the AIA trial regime did not open until 2012-09-16. A defendant facing assertion should lead with expiry and the resulting inability to recover post-expiration damages, not with an invalidity theory built on a nonexistent IPR record. If you nonetheless want an administrative bite at the family, note the Board can institute IPR against expired claims (patent owner simply cannot amend) — but there is little practical upside once the term is over and no injunctive relief is available.

Strategic summary

Canceled vs. sustained vs. untested. None of claims 1–6 of US 6,291,170 has been canceled, sustained, or even construed by the PTAB, because no AIA trial was ever filed. All six claims are technically untested in post-grant proceedings. Practically, they are also unenforceable going forward: the patent's adjusted expiration was 2009-09-23, so damages can only reach pre-expiration conduct, and the six-year § 286 lookback from today (2026-09-11) reaches back only to 2020 — after expiry. Subject to laches/§ 286 and any state-law tolling arguments, a damages case on the '170 patent is essentially time-barred by arithmetic.

Estoppel landscape. § 315(e)(2) estoppel is not a factor — no petitioner ever instituted an IPR or PGR, so there is no petitioner or privy carrying estoppel, and no ground was "raised or reasonably could have been raised" in an AIA trial. Practically this cuts both ways: a defendant is not boxed in by anyone else's IPR, but also cannot free-ride on an earlier cancellation. Any invalidity position must be built in district court (or not at all), on § 102/§ 103/§ 112 grounds of your own choosing, against a 1989-priority patent.

Pattern signals. No repeat-petitioner pattern (no petitioners at all). No defensive aggregator (e.g., Unified Patents) appears anywhere in the record for this patent or its family. The patent owner — the Board of Trustees of Leland Stanford Junior University — has not needed to defend the '170 patent at the PTAB, which is unsurprising for a university-owned research-tool patent that expired before the AIA trial regime matured. The one trace of contested history is the family's Darts-IP litigation flag noted above; it is a litigation signal, not a post-grant one, and I have not verified it.

A practitioner note on the claims themselves. If you are forced to litigate (e.g., on a pre-expiration contract or license theory), the claim set has a visible drafting weakness that no tribunal has ever addressed: claim 5 depends from claim 1 and recites "the single cell is a neural cell," but claim 1 is not limited to a single cell — claim 4 is the single-cell profile. Claim 6 in turn depends from claim 5. That antecedent-basis/§ 112 gap has never been litigated and is a candidate for a district-court indefiniteness or improper-dependent-claim attack, but it is untested and I would not treat it as a certainty.

Recommended next steps

• No PTAB activity exists, and none can now arise in a practical sense. State that plainly in any client memo: the '170 patent has never been challenged in an AIA trial, the family members (US 5,545,522; US 5,716,785; US 5,891,636; US 7,049,102) have never been challenged either, and the '170 patent expired 2009-09-23 — before IPR/PGR/CBM existed.
• Lead with expiry, not invalidity. Confirm the expiration date against the USPTO Patent Center maintenance-fee record and the face of the patent, then map any asserted conduct to its date. If all accused conduct postdates 2009-09-23, there is no infringement remedy for that conduct.
• Verify the Darts-IP litigation lead before relying on anything. Pull Darts-IP family 23628663 and the corresponding district-court docket (CourtListener / PACER) to identify the parties, forum, and outcome. If the family litigation involved a licensee or a predecessor entity, it may bear on ownership, standing, or license defenses. I could not confirm these details and am not asserting them.
• If you want an administrative challenge for family-mates, note that US 7,049,102 (granted 2006-05-23) is the youngest family member and also expired around the same 2009 term; check its exact expiration before spending on a petition. Filing an IPR against expired claims is legally possible (the Board has instituted such trials; the patent owner just cannot amend), but a trial that cannot produce injunctive or forward-looking relief rarely justifies the cost — especially where a § 286 damages bar likely resolves the case first.
• Primary sources to cite in a memo: the patent's Google Patents record (https://patents.google.com/patent/US6291170/en) for term, assignee, and claim text; USPTO PTAB E2E (https://e2e.uspto.gov) and the PTAB Decisions page to confirm the empty proceeding list; CourtListener (https://www.courtlistener.com) for any CAFC or district-court docket once you resolve the Darts-IP lead.

Accuracy note: I did not find, and have not invented, any proceeding number, panel, FWD, or appeal for this patent. Everything above is drawn from the structured "PTAB proceedings on file" block and the Google Patents record supplied, plus web searches that returned no AIA proceeding for US 6,291,170 or its family. The Darts-IP litigation indicator is the one unverified item, and it is flagged as such.

I'll research the assignment record and litigation history for US 6291170 before building the report.

Ownership & Assignment Analysis — US 6,291,170 B1 ("Multi-genes expression profile")

Data-retrieval note (read first): I could not complete a live pull of the USPTO Patent Assignment Center record set for this patent within this session — the searches I ran returned no indexed reel/frame entries, and my queries against assignment-center indexes were cut short. I therefore have no verified reel/frame numbers to cite. Per the operating rules, I will not invent them. Everything below is limited to what is verifiable from the patent document itself, Google Patents legal events, and public corporate/litigation context; unretrieved items are marked unverified.

Inventors

All four were Stanford personnel at the 1989-09-22 priority date; the aRNA method traces to Eberwine et al., PNAS (1992), "Analysis of gene expression in single live neurons." The MO/NY addresses are the post-1989 (issue-era) correspondents' addresses, not filing addresses — a common artifact of long-lived continuations.

Unusual pattern check: All four inventors left Stanford within roughly 2–5 years of filing (Barchas → Cornell, ~1991; Eberwine → Penn, ~1991; Von Zastrow → UCSF, ~1993; Van Gelder → WashU, ~1994). This is normal academic migration, not the "all inventors exit within 12 months" precursor to a portfolio fire-sale — and critically, Stanford retained title, which it could not have done in a fire-sale scenario.

Original assignee

The Board of Trustees of the Leland Stanford Junior University (Stanford, CA) — listed as both original and current assignee on Google Patents.

• Product: None. Stanford does not manufacture or sell a product embodying the claims. The technology was commercialized by licensees (the aRNA/T7-amplification chemistry is a foundational input to GeneChip-style amplification, NuGEN, and similar kits), with licensing handled by Stanford's Office of Technology Licensing (OTL).
• Primary line of business: Higher education / academic research; patent licensing as an ancillary function.
• Current status: Operating. Not acquired, not dissolved, not in bankruptcy.

Assignment timeline

The Assignment Center record set could not be retrieved in this session. What is verifiable:

• The issued patent's front page names Board of Trustees of Leland Stanford University as assignee, so title was with Stanford at issuance (2001-09-18). An inventor→Stanford "Assignment of Assignors' Interest" against the original 1989 application and/or its continuations is expected as a matter of standard university practice, but I cannot cite reel/frame for it, and I am not going to guess a recording.
• Google Patents legal events for US 6,291,170 list no post-issuance assignment whatsoever. The only events are: application filed by Leland Stanford Junior University → priority claim → application granted (2001-09-18) → publication → adjusted expiration (2009-09-23). There is no "Assigned to" event transferring the patent away from Stanford.
• The related continuation US 7,049,102 (filed 2000-11-15, granted 2006-05-23) likewise shows Stanford as assignee.

Net finding: there is no evidence of any post-issuance ownership change. On the available record, Stanford owned this patent from issuance to expiry (adjusted expiration 2009-09-23).

If you need the reel/frame confirmed, search "6291170" at https://assignmentcenter.uspto.gov/ (or https://assignment.uspto.gov/patent/index.html) — the only record you should expect to find is an inventor→Stanford assignment plus, possibly, a later confirmatory assignment for the 09/286,533 continuation.

Timeline diagram

timeline
    title Ownership of US 6291170
    1989 : Priority application filed Sep 22
         : Inventors assigned rights to Stanford
    1996 : Parent patent US5545522 issues
    1998 : Parent patent US5716785 issues
    1999 : Continuation application filed Apr 5
    2001 : US6291170 issues Sep 18
    2006 : Sibling continuation US7049102 issues
    2009 : Patent expires Sep 23

NPE / troll-pattern signals

Verdict

Insufficient data (no records beyond the original inventor→Stanford assignment).

Justification: the issued patent names The Board of Trustees of the Leland Stanford Junior University as assignee, Google Patents lists no post-issuance assignment event for US 6,291,170, and the patent expired 2009-09-23 — so the record shows a single owner with no shell-entity transfer, no cascading LLC chain, and no NPE in the chain. None of the eight signature troll patterns is made out on the available evidence; the one open item is the family's litigation flag, which I could not resolve to a specific case. Note the taxonomic nuance: Stanford is a non-practicing owner in the literal sense (a university, not a manufacturer), so if the flagged litigation is a Stanford assertion, this is a university-enforcement posture — categorically distinct from the anonymous-LLC asserter pattern this rubric targets, since the enforcer name is not concealed and title never left the university.

Verify at: https://assignmentcenter.uspto.gov/ (search "6291170") · https://assignment.uspto.gov/patent/index.html · https://patents.google.com/patent/US6291170/en (legal events)

Caveats on this analysis

• No reel/frame citations are given because none were retrieved. Treat every "recorded assignment" statement above as absence of evidence in the sources I could reach, not as a certified null result from the Assignment Center.
• The "Family has litigation" flag on Google Patents is a real data point I observed but could not tie to a specific docket or plaintiff; do not rely on my characterization of it as a Stanford assertion without checking PACER/Docket Navigator.
• I did not retrieve SEC filings for any entity here because no public-company assignor or assignee appears in the chain.

I'll search for the specific patent's citation records and prior art.

Scope, sources, and one hard limit (stated up front)

Target confirmed as US 6,291,170 B1 ("Multi-genes expression profile"; App. 09/286,533; filed 1999‑04‑05; granted 2001‑09‑18; assignee Board of Trustees of Leland Stanford Junior University). I retrieved its front‑page "US Patent References" list in partial form from FreePatentsOnline (https://FreePatentsOnline.com/[6291170](/patent/6291170).html) and corroborating family/IDS material from the Unified Patents portal, Google Patents (https://patents.google.com/patent/US6291170/en), and Altmetrics. The FreePatentsOnline citation list was truncated mid‑entry at US 5,132,418, and I was unable to load the complete USPTO front page (PatentCenter/Patent Public Search) within this session. So the table below is complete down to US 5,132,418 and then cuts off. I am flagging this rather than padding the list. Everything below is either directly retrieved or explicitly labelled as inferred.

Non‑matches I deliberately excluded (per your "do not return similar numbers" instruction)

Threshold issue that governs the entire § 102 analysis

US 6,291,170 is the last of a four‑generation continuation chain claiming priority to 1989‑09‑22 (Ser. 07/411,370, abandoned → 07/957,647 → US 5,545,522 → 08/636,748 → US 5,716,785 → 08/922,965 → US 5,891,636 → 09/286,533 → US 6,291,170). Two tracks follow, and they give opposite answers:

Track A — claims take the 1989‑09‑22 priority date. Then every reference in the table below is post‑dated: the earliest is US 5,132,418 (1992‑07‑21) and the non‑patent literature is 1983–1991-at-earliest for the newer items. Nothing published after the invention date can be § 102(a) or § 102(b) art, and § 102(e) art requires the reference's own filing date to predate the applicant's invention — implausible against a 1989 date. Under Track A, none of the cited references is § 102 prior art at all, and the examiner's citations functioned as background/§ 103 context rather than as anticipatory art.

Track B — the priority claim fails for a given claim. The asserted claims are drafted as a product/assembly ("a multi‑gene expression profile … comprising a hybridizing target; and a hybridizing probe"), a formulation that does not appear in the 1989 disclosure, which is entirely directed to methods of producing amplified antisense RNA. If a claim is not supported under § 112(a) by the 1989 parent, its effective date becomes 1999‑04‑05, and every reference below (all issued/published more than one year earlier) becomes § 102(b) prior art. This is, in my assessment, the only route by which the cited art bites — and it is a real one, precisely because claims 1 and 4 are product claims in a patent whose specification is a method disclosure.

I cannot resolve Track A vs. Track B from the record retrieved; no reissue, reexam, IPR, or court construction of these claims was found (consistent with the earlier litigation section's finding that the family carries only an unresolved Darts‑ip litigation flag, family ID 23628663). My § 102 mapping below is therefore analytical inference, not a statement of what the examiner applied.

Table 1 — US Patent References cited on the face of US 6,291,170 (retrieved portion)

Publication dates are the issue dates as listed; the FreePatentsOnline citation listing does not give the cited patents' own filing dates, and I will not invent them.

Also cited within the specification text itself (these are the classic PCR/oligo‑synthesis authorities and are almost certainly the balance of the truncated front‑page list): US 4,683,202 and US 4,683,195 (Mullis et al., PCR — both expressly incorporated by reference in the Background), US 4,458,066 (synthesis of oligonucleotides on a modified solid support), US 4,755,619 (labelling techniques). I flag these as specification‑cited, front‑page status unverified rather than asserting they appear on the face.

Table 2 — Non‑patent literature cited (from the specification and the family IDS)

Verified as cited in the US 6,291,170 specification: Gubler & Hoffman, Gene 25:263‑269 (1983); Frohman et al., PNAS 85:8998‑9002 (1988); Gould et al., PNAS 86:1934‑1938 (1989); Sarkar et al., Science 244:331‑334 (1989); Stoflet et al., Science 239:491 (1988); Melton et al., NAR 12:7035‑7056 (1984); Krieg et al., NAR 12:7057‑7070 (1984); Milligan et al., NAR 15:8783‑8798 (1987); Dunn & Studier, J. Mol. Biol. 166:477‑535 (1983) and 175:111‑112 (1984); Rosenberg et al., Gene 56:125‑135 (1987); Chamberlin & Ryan, in The Enzymes (1982); Duguid et al., PNAS 85:5738‑5742 (1988); Sive & St. John, NAR 16:10937 (1988); Tecott et al., Science 240:1661‑1664 (1988); Eberwine et al., Neuroscience Short Course I 69‑81 (1988); Chirgwin et al., Biochemistry 24:5294‑5299 (1987); Van Ness et al., NAR 10:8061‑8077 (1982); Sutcliffe et al., CSH Symp. Quant. Biol. 48:477‑484 (1983); Nudel et al., NAR 11:1756‑1771 (1983); Jones et al., J. Biol. Chem. 262:14241‑14249 (1987); Gruol et al., J. Neurosci. 7:1271‑1293 (1987); Yool et al., J. Neurosci. 8:1971‑1980 (1988); Wickstrom, J. Biochem. Biophys. Methods 13:97‑102 (1986); Gilman, Ann. Rev. Biochem. 56:615‑649 (1987); Gierschik et al., PNAS 83:2258‑2262 (1986); Largent et al., PNAS 85:2864‑2868 (1988); Beaucage et al., Tet. Lett. 22:1359 (1981); Maniatis et al., Molecular Cloning (1982); Alberts et al., Molecular Biology of the Cell, 2d ed. (1989); Watson et al., Molecular Biology of the Gene, 4th ed.; Varmus, Science 240:1427‑1435 (1988).

Additional family IDS items (retrieved from the Unified Patents records for the siblings US 5,545,522 and US 5,891,636, so attributed to the family, not verified as being on 6,291,170's own face): Hames et al., Nucleic Acid Hybridization, IRL Press (1985); Sargent, Methods in Enzymology vol. 152 (1987) 423‑433; Feinberg & Vogelstein, Anal. Biochem. 132:6‑13 (1983); Belldegrun et al., Cancer Immunol. Immunother. 31:1‑10 (1990); Efstratiadis et al., Cell 7:279‑288 (1976); Berger et al., Biochemistry 22:2365‑2372 (1983); Milner & Sutcliffe, NAR 11:5497‑5521 (1983); Huang & Hershey, Mol. Cell. Biol. 9:3679‑3684 (1989); Harlan, Mol. Neurobiol. 2:183‑200 (1988); Craig et al., Neuron 10:1055‑1068 (1993); Nair et al., J. Neurosci. 18:2685‑2696 (1988); Meyers et al., Cancer 67:2087‑2095 (1991); Davis et al., DNA Cell Biol. 14:833‑839 (1995).

One further NPL item is confirmed as cited by US 6,291,170 B1 per Altmetric: "An improved method for chromosome‑specific labeling of α satellite DNA in situ by using denatured double‑stranded DNA probes as primers in a primed in situ labeling (PRINS) procedure," Genetic Analysis: Biomolecular Engineering, Sept. 1991 (https://www.altmetric.com/details/41519056/patents).

Most relevant prior art, ranked, with § 102 claim mapping

Assuming Track B (priority broken for the product claims), the references that go to the heart of the asserted subject matter are these five:

1. US 5,459,037 — Sutcliffe, "Method for simultaneous identification of differentially expressed mRNAs and measurement of relative concentrations," 1995‑10‑17 (435/6). This is the closest conceptual hit on claims 1 and 4: simultaneous, multi‑transcript readout plus relative‑concentration measurement maps onto "a multi‑gene expression profile" and "each have a relative abundance which qualitatively reflects the relative representation of specific nucleic acid messages within the sample." The only surviving distinction is the claimed assembly framing (an amplified promoter‑primed population paired with a hybridizing target). If § 102 fails on the product/method form, this is the primary § 103 reference.

2. US 5,665,547 — Pardee, "Methods of comparing levels or amounts of mRNAs," 1997‑09‑09 (435/6). Second closest on claims 1 and 4, aimed squarely at comparing mRNA levels — i.e., the "qualitatively reflects the relative representation" limitation.

3. US 5,514,545 — Eberwine, "Method for characterizing single cells based on RNA amplification for diagnostics and therapeutics," 1996‑05‑07 (435/6). Goes directly to claims 4, 5 and (via claim 5) 6 — single‑cell RNA amplification. Note the § 102(c)/(a) wrinkle: Eberwine is a named inventor on US 6,291,170, so this reference is the applicants' own earlier work; it is not "by another" for § 102(a) purposes, and its real bite is as § 102(b) art (issued >1 year before the 1999 filing) or as an obviousness/§ 102(e)‑type reference if the priority chain fails. The prosecution history here would be the thing to check.

4. US 5,554,517 (Davey, 1996‑09‑10) / US 5,409,818 (Davey, 1995‑04‑25) / US 5,399,491 and US 5,888,779 (Kacian, 1995‑03‑21 / 1999‑03‑30) / US 5,437,990 (Burg, 1995‑08‑01) / US 5,783,391, 5,622,820, 5,869,249 (Rossi). This cluster discloses promoter‑driven, RNA‑polymerase‑mediated in vitro amplification, which is the mechanical core of the "amplified in vitro simultaneously with RNA polymerase and a single primer linked to a RNA polymerase promoter" limitation. My assessment: these are § 103 rather than § 102(b) art for claim 1/3, because the NASBA/transcription‑amplification systems of that era (Kacian 5,399,491; Davey 5,540,818/5,554,517) characteristically employ two or more primers, at least one bearing the promoter — so they do not disclose the claimed "single primer linked to a RNA polymerase promoter" combined with a heterogeneous, broad‑class message population. To succeed on § 102 an examiner or challenger would have to show the reference discloses the whole claimed assembly as arranged; that is not apparent from the titles alone, and I have not retrieved full texts.

5. The array/"hybridizing target" family — US 5,143,854 (Pirrung, 1992‑09‑01), US 5,489,678 (Fodor, 1996‑02‑06), US 5,384,261 (Winkler, 1995‑01‑24), US 5,175,209 (Beattie, 1992‑12‑29). These supply the "hybridizing target" element of claims 1 and 4 — i.e., an immobilized/capture target surface. Alone they do not anticipate; combined with any of items 1–4 they are the natural § 103 combination the examiner would have had available for a "profile = probe + target" claim.

Secondary, single‑claim references: US 5,175,103 (Lee, 1992‑12‑29) → claim 5 ("neural cell"); US 5,569,584 (Augenlicht, 1996‑10‑29) → claim 6 ("state" of tissue); US 5,281,519 (Schechter, 1994‑01‑25) → the thalassemia diagnostic embodiment recited in the specification and echoed in the "quantitative resolution" passages; US 5,348,855 (Dattagupta) and US 5,487,970 (Rowley) → general hybridization‑assay/diagnostic context for claim 1. US 5,221,518, US 5,210,264, US 5,198,368, US 5,174,962, RE 34,069, US 5,132,418, US 4,458,066, US 4,755,619 are oligonucleotide‑synthesis, sequencing‑apparatus and labelling references; they are background, and I see no claim they could anticipate on their own.

What I could not verify (and will not assert)

1. Completeness of the citation list. FreePatentsOnline's "US Patent References" block for 6291170 was retrieved only down to US 5,132,418; entries below that (and the full count) are unknown to me. The three Mullis/organic‑chemistry references above are confirmed only as specification citations.
2. Whether each citation is an examiner or applicant (IDS) citation. The listings I reached do not distinguish these, and the family IDS material I retrieved belongs to the siblings (5,545,522; 5,891,636) as much as to 6,291,170.
3. Filing dates of the cited patents — not present in the retrieved listing, so I have not supplied them.
4. The § 102 subsection actually applied. The front page does not state it; my mapping is an analytical inference keyed to the priority‑date question above.
5. Full texts of the five "most relevant" references. My claim mapping rests on the titles/classifications and family context, not on reading each reference. Before relying on any § 102 conclusion, the full text of US 5,459,037 and US 5,665,547 in particular should be pulled.

Bottom line: The citation set is dominated by (i) transcription/promoter‑based amplification patents (Kacian, Davey, Burg, Rossi), (ii) multi‑message differential‑expression methods (Sutcliffe, Pardee — the closest to claims 1 and 4), (iii) the applicants' own single‑cell RNA‑amplification work (Eberwine US 5,514,545 — the closest to claims 4–6), and (iv) oligonucleotide‑array/"target" chemistry (Pirrung, Fodor, Winkler, Beattie). The single most consequential fact for any § 102 attack is not any individual reference but the 1989‑09‑22 priority chain: if the product‑form claims 1 and 4 are entitled to it, none of these post‑1989 references is anticipatory art, and the entire analysis shifts to whether the "multi‑gene expression profile" claims have § 112(a) support in the 1989 disclosure.

I'll ground the obviousness analysis in the prior-art references identified on this patent's page (cited references in the specification, the "Prior art keywords," and family/citing art) before assembling combinations.

Excellent — key find: the FreePatentsOnline record lists "US Patent References" on this patent's face. Let me pull the full reference list and check the dates of those references, since their post-1989 dates bear directly on the §103 analysis.

§103 Obviousness Analysis — US 6,291,170 B1 ("Multi-genes expression profile")

Building on the earlier summary and litigation sections (which I do not repeat). Where those sections flagged the product-by-assembly claim format and the claim-5 antecedent defect, I cross-reference rather than restate.

0. Two threshold issues that control everything below

0.1 Which prior art universe applies. Google Patents carries a "prior art date" of 1989-09-22 for this document (https://patents.google.com/patent/US6291170/en), and the title page states priority to 1989-09-22. But the actual filing date is 1999-04-05 (app. 09/286,533). The entire §103 answer turns on whether the six granted claims — which are drawn to a "multi-gene expression profile" product/assembly, not to the amplification method the 1989 disclosure describes — are supported under §112(a) by the 1989 parent. If they are, the art cutoff is 1989. If they are not (a real risk, since the word "profile" and the claim architecture appear nowhere in the 1989-lane disclosure), the effective date is 1999-04-05 and a large body of 1990s art becomes available.

Critically, the two-statement difference matters empirically: the FreePatentsOnline record for this patent lists a "US Patent References" set whose members issued between 1994 and 1999 (https://FreePatentsOnline.com/[6291170](/patent/6291170).html), i.e., all after the 1989 priority date:

(FPO's list is truncated in what I could retrieve after US 5,281,519, so there may be more.)

Why this is the crux: references issued 1994–1999 cannot be §102 art against a claim entitled to 1989-09-22. Either the Examiner treated some claims as not entitled to the 1989 date, or these were cited as background/authorities rather than applied art. I could not retrieve the file wrapper to resolve this, and I flag it as an unverified but outcome-determinative question. Note also the internal-consistency point: two of these are the same institution's own later work (Eberwine's 5,514,545; Sutcliffe's 5,459,037) — the sibling-art relationship is worth verifying in PatentCenter.

0.2 Claim construction. Both independent claims (1, 4) recite a made probe population by the process that made it ("amplified in vitro simultaneously with RNA polymerase and a single primer linked to a RNA polymerase promoter") coupled to a functional result ("relative abundance which qualitatively reflects…"). Under In re Thorpe / Abbott v. Sandoz, process limitations in a product claim get patentable weight only to the extent they impart a distinct structural/functional character. Here there is no asserted structural difference over prior-art amplified probe populations — only the provenance of the probe and an inherent consequence of the amplification chemistry. That substantially collapses the gap between the claims and the art.

1. The prior art available (from the patent's own prior-art section, its cited references, and its front-page reference list)

The Google Patents "Prior art keywords" for this document are cdna, rna, nucleic acid, arna, primer (https://patents.google.com/patent/US6291170/en) — i.e., the examiner's own framing of the field. The substantive art falls into three clusters.

Cluster A — promoter-driven transcription (the amplification engine)

• Melton et al., Nucl. Acids Res. 12(18):7035–7056 (25 Sep 1984) (DOI 10.1093/nar/12.18.7035; PMCID PMC320141). In vitro transcription from a bacteriophage SP6 promoter to make "pure single stranded RNAs of virtually any structure"; expressly teaches that these RNAs are useful as "probes for nucleic acid blot and solution hybridizations," that they have "high specific activity," and that they "significantly increase the sensitivity of nucleic acid hybridization methods." This is the "hybridizing probe" element, verbatim.
• Sarkar & Sommer, Nucl. Acids Res. 16:5197 (1988) — the RAWTS protocol. Its first-strand step is a single oligo-dT primer: "50 µg/ml oligo d(T)12-18 … and 1000 U/ml AMV reverse transcriptase"; the promoter is carried on a primer; transcription with T7 RNA polymerase follows.
• Sarkar & Sommer, Science 244:331–334 (21 Apr 1989) (DOI 10.1126/science.2565599). RAWTS = "cDNA synthesis, PCR with a primer or primers containing a phage promoter, transcription from the phage promoter, and reverse transcriptase-mediated sequencing." It was used to survey four different mRNAs across four different cell types — i.e., a multi-gene/multi-sample expression readout.
• Stoflet, Koeberl, Sarkar & Sommer, Science 239:491–494 (1988) — GAWTS; the parent technique, whose stated advantage includes that "the rate … can be increased by coamplification and cotranscription of multiple regions." That is a direct teaching of multiplexed promoter-based amplification.
• Milligan et al., Nuc. Acids Res. 15:8783–8798 (1987) — T7 RNA polymerase on synthetic DNA templates (cited in the patent itself).
• Chamberlin et al., J. Biol. Chem. 248:2235 (1973); Chamberlin & Ryan, The Enzymes (1982) — T7 specificity for its cognate promoter.
• Rosenberg et al., Gene 56:125–135 (1987) — absence of efficient T7 termination signals ⇒ transcripts from almost any DNA. This is the predictability teaching: broad, unbiased transcription of a heterogeneous template pool.

Cluster B — cDNA synthesis and unbiased priming

• U.S. Pat. Nos. 4,683,202 and 4,683,195 (Mullis) — PCR (cited on the face of the patent as "incorporated herein by reference").
• Gubler & Hoffman, Gene 25:263–269 (1983) — RNase H / E. coli DNA pol I second-strand synthesis, i.e., the routine step that converts the primer-bearing first strand into a double-stranded promoter.
• Frohman et al., PNAS 85:3998–4002 (1988) and Gould et al., PNAS 86:1934–1938 (1989) — homopolymeric tailing and degenerate primers for amplifying sequences without knowing both termini.

Cluster C — expression comparison / differential readout and small-sample sampling

• Duguid et al., PNAS 85:5738–5742 (1988) and Sive & St. John, Nuc. Acids Res. 16:10937 (1988) — labeled RNA populations used as hybridization probes/drivers; subtractive hybridization to find differentially expressed sequences.
• Van Ness et al., Nuc. Acids Res. 10:8061–8077 (1982) — Rot hybridization (relative abundance measurement).
• Tecott et al., Science 240:1661–1664 (1988) — in situ transcription (IST): reverse transcription of mRNAs within fixed tissue sections; the same line of work reports that "[i]ntermediate lobe signal intensities were sensitive to dopaminergic drugs, demonstrating that the method can be used for studies of mRNA regulation" (via the reference list snippet at https://www.semanticscholar.org/paper/…a6f5a5fe0d2d1e3f2a1bbfc40c63cb579f30346d).
• Eberwine et al., Neuroscience Short Course I (Soc. Neurosci.) 69–81 (1988) — IST reaction conditions.
• Largent et al., PNAS 85:2864–2868 (1988) — in situ hybridization showing region-specific G-protein α-subunit mRNA abundance in brain.

Cluster D — post-1989 US patents (available only if the effective date is 1999-04-05)

• Eberwine, US 5,514,545 — characterizing single cells based on RNA amplification.
• Sutcliffe, US 5,459,037 — simultaneous identification of differentially expressed mRNAs and measurement of relative concentrations (i.e., a "multi-gene expression profile" with quantitative readout).
• Pardee, US 5,665,547 — comparing levels/amounts of mRNAs. (Also Pardee US 5,965,409, "System for comparing levels or amounts of mRNAs," 1999-10 — appears in a related citation list; I could not confirm it is on this patent's face.)
• Kacian US 5,399,491 / 5,888,779; Davey US 5,409,818 / 5,554,517; Rossi US 5,622,820 / 5,783,391 / 5,869,249 — transcription-based amplification using a promoter-bearing primer (NASBA/3SR lineage).
• Augenlicht US 5,569,584 — distinguishing tissue state by expression.
• Fodor US 5,489,678; Winkler US 5,384,261 — array/immobilized-probe formats (the physical target for a "profile").

2. Combination A — the dispositive primary combination against claim 1

Sarkar & Sommer 1988/1989 (RAWTS) + Melton et al. 1984 + Gubler & Hoffman 1983 + Mullis 4,683,202

Motivation to combine (rationales cognizable under KSR / MPEP 2143):

1. Same field, same problem, same elements. Melton and Sarkar are both about producing abundant, single-stranded, promoter-driven RNA from DNA templates for hybridization or sequencing; they are from the identical art and combinable with a reasonable expectation of success.
2. Sarkar supplies the promoter-in-primer idea; Melton supplies a better reason to use it than sequencing — probing. Melton expressly teaches that in-vitro-transcribed RNA is the preferred hybridization probe because of high specific activity and increased sensitivity — exactly the claim-1 "hybridizing probe."
3. The patent's own background supplies the motivation to drop PCR. The specification recites, as known art problems: (i) PCR "typically requires that 5′ terminus and 3′ terminus sequence information be known"; (ii) Taq's "low fidelity" propagates misincorporations; (iii) "sequences longer than 3 kilobases create difficulties"; (iv) "PCR provides amplification by DNA replication and not by transcription." These are applicant-admitted deficiencies, and they are legally available to show why a POSITA would replace RAWTS's PCR step with pure transcription-based amplification.
4. The "single primer" limitation is the natural simplification, not an invention. Once the PCR step is recognized as unnecessary (the transcription reaction is itself the amplifier — Melton), the promoter-bearing primer need not be one of a PCR pair; Sarkar's own first strand is already made with a single oligo-dT primer. Under KSR, where there is "a finite number of identified, predictable solutions," the choice of a single promoter-bearing oligo-dT primer is obvious to try.
5. Gubler & Hoffman supplies the routine second-strand step (the patent prints it as the standard technique) needed to convert the first strand into a functional double-stranded promoter.

Conclusion: Claim 1 as a whole would have been obvious over Sarkar + Melton + Gubler & Hoffman in view of Mullis. The only element requiring genuine argument is "a single primer," and the argument is weak given applicant's own admissions and Melton's teaching that transcription alone amplifies.

3. Combination B — the "multi-gene" / "profile" character

Melton 1984 + Stoflet 1988 + Duguid 1988 + Van Ness 1982, optionally + Sutcliffe '037 / Pardee '547 (1999-date theory).

• "Multi-gene" is taught by Stoflet's coamplification/cotranscription of multiple regions and by Sarkar 1989's four-mRNA, four-cell-type survey.
• "Expression profile" as a comparative readout is taught by Duguid 1988 (probe populations in subtractive/differential hybridization) and Van Ness 1982 (Rot quantitation of relative representation), with Tecott 1988 and Largent 1988 supplying the neurobiological application.
• If the claims are only entitled to 1999, Sutcliffe '037 is effectively dispositive for the "multi-gene profile" concept (simultaneous identification of differentially expressed mRNAs plus measurement of relative concentrations) and Pardee '547 is dispositive for "comparing levels or amounts of mRNAs." I would expect a validity challenge to lead with these under the later-date theory.
• Motivation: the same as Combination A, plus the patent's own stated research driver — cloning and analyzing low-abundance, spatially restricted messages in brain; array/probe technology (Winkler '261, Fodor '678) supplied the physical target.

4. Combination C — claim 4 (single-cell profile)

Tecott 1988 (IST) + Eberwine 1988 (IST conditions) + Melton 1984 / Sarkar 1988

Tecott teaches making cDNA in situ from fixed tissue, including minute samples, and explicitly frames the method as usable for mRNA regulation studies and drug-sensitive signal changes. Combining that sampling/priming chemistry with Sarkar/Melton's promoter-driven amplification yields an amplified message population from a small/single-cell sample to be hybridized to a target. The patent's own background states the problem — "the identification and cloning of novel regulated messages from discrete cell populations has proven to be a formidable task" — which supplies the motivation.

If the 1999-04-05 date governs, US 5,514,545 (Eberwine, "Method for characterizing single cells based on RNA amplification for diagnostics and therapeutics") stands essentially as a §102/§103 reference against claim 4 and, with Largent 1988 or Tecott 1988, against claim 5 (neural cell). This is the single most important unverified dependency in the analysis.

5. Combination D — claims 5 and 6

• Claim 5 ("the single cell is a neural cell") adds only an intended-tissue limitation. Largent 1988 (in situ hybridization of G-protein α-subunit mRNAs in brain regions), Tecott 1988 (cerebellar/neuroendocrine tissue) and the patent's own background (brain nuclei, granule-cell layer) supply "neural cell." Under MPEP 2111.02, a "wherein" clause that merely states the intended use of the same structure does not patentably distinguish. Note also the antecedent-basis defect already flagged in the summary (claim 5 depends from claim 1, which has no "single cell"); that defect makes claim 5's scope ambiguous and, at minimum, does not rescue it on the merits.
• Claim 6 ("relative level of representation varies as a function of arousal state, behavior, drug treatment or development") is a statement of the use/phenomenon to be observed, not a structural or functional difference in the profile. Tecott 1988 (drug sensitivity of transcription signals) and the patent's own background ("identification of mRNAs which vary as a function of arousal state, behavior, drug treatment, and development … has been hindered") show this was an art-recognized application. Nothing in claim 6 changes the product; it is obvious over Combination A/D plus the admitted state of the art.

6. Why "qualitatively reflects the relative representation" is not a saving limitation

This is the element most likely to be argued, and it is the weakest.

1. Inherency. Melton's transcription is a linear, promoter-initiated, non-replicative process; transcribing a heterogeneous cDNA pool therefore necessarily produces a transcript population whose relative abundances track the cDNA pool, and (through the priming step) the parent RNA. The specification itself says "aRNA production appears to be linear" and that "aRNA abundance is representative of the parent cDNA" — the applicant's own description of the result as an inherent property of the prior-art chemistry. Where the claimed property is inherent in the prior-art product, the burden shifts to the applicant to show unexpected results (In re Best; In re Kratz; MPEP 2112). No unexpected-results evidence appears anywhere in the record I could retrieve (the patent's own data — ~80-fold molar amplification, size distribution matched to parent cDNA, 30% of signal in rRNA bands in proportion to cDNA yield — affirm the expected result).
2. Predictability. In re O'Farrell and KSR: a result that flows predictably from performing known steps is not patentable. Rosenberg 1987 (no termination signals ⇒ transcription of almost any DNA) makes the breadth and representativeness of the transcript pool predictable, not surprising.
3. Mere result / no independent weight. A "profile" that exists only upon hybridization of probe to target adds nothing beyond the expected operation of the two known components.

7. The patentee's best counterarguments, and my assessment

I am not aware of any secondary-consideration evidence (unexpected results, commercial success, nexus, licensing) in the record I could retrieve, and I will not assume any exists.

8. Claim-by-claim verdict (as a technical analyst, not a legal opinion)

9. Things I could not verify (stated explicitly)

1. Prosecution history / file wrapper for 09/286,533 — I could not retrieve the examiner's cited art or any §103 rejection. Everything above is my own reconstruction from the patent's face, its specification citations, and the FPO reference list.
2. The Google Patents "References Cited" block was truncated in the version I retrieved; and the FPO "US Patent References" list is cut off after US 5,281,519. The lists above may be incomplete.
3. Whether the 1994–1999 face references were applied or merely listed — decisive for the priority-date question in §0.1, and unresolved.
4. US 5,965,409 (Pardee) and US 6,255,060 (Eberwine et al.) appeared in a related patent's citation list, not confirmed as on the face of 6,291,170 — I have not treated them as such.
5. Van Gelder et al., PNAS 87(5):1663–1667 (March 1990) — the inventors' own paper disclosing the T7-promoter/oligo-dT/aRNA method — is not prior art here (published after the 1989-09-22 priority date), and must not be used as §103 art. I note it only because the search results confirm the method's 1990 publication, which is relevant if the priority date is ever lost.
6. No secondary-considerations evidence located.

Net assessment: taking the prior-art record at face value, claim 1 (and dependents 2, 3) would have been prima facie obvious over Sarkar + Melton + Gubler & Hoffman, with the "single primer" and "qualitatively reflects" limitations answerable by applicant's own admitted PCR drawbacks, by Rosenberg's teaching of untemplated-termination transcription, and by inherency (In re Best). Claims 4–6 are obvious on the same record with Tecott/Largent, and become far weaker still if the claims are measured against a 1999-04-05 effective date rather than 1989-09-22.