US 7371580

Summary — U.S. Patent 7,371,580 (US7371580B2)

Authoritative bibliographic data (verified)

Abstract (verbatim)

"The present invention provides a system and methods for assaying nucleic acid molecules with reduced levels of background signal and enhanced specificity and sensitivity. In particular, the present invention provides a system and methods for detecting, sorting, tracking and characterizing nucleic acid molecules using hybridization assays with reduced levels of undesirable cross hybridization and reduced levels of intramolecular secondary structure."

Plain-language technology overview

The patent is directed to universal addressable-array (tag/anti-tag) hybridization assays. In such assays, "intermediary" nucleic acid molecules carry (i) a tag region that binds to a spatially addressable anti-tag probe on an array, and (ii) an anti-target region that binds to a target nucleic acid of interest in a sample. A known failure mode is cross-hybridization — e.g., anti-target regions of the intermediary molecules undesirably pairing with anti-tag probes on the array, causing false signals and reducing assay sensitivity/multiplexing capacity.

The invention solves this using "unstructured nucleic acids" (UNAs) — nucleotides with modified bases/sugars (e.g., 2-aminoadenosine (D), 2-thiothymidine, inosine (I), pyrrolo-pyrimidine (P)) chosen so that complementary UNA-vs-UNA base pairs are destabilized (reduced hydrogen bonding), while each UNA still hybridizes normally to natural (or differently modified) complements. Thus:

• anti-tag probes and anti-target regions are both built with UNA chemistry, so they have a reduced tendency to bind each other, while
• the anti-tag still binds its intended tag, and the anti-target still binds its intended natural target.

This reduces background/cross-hybridization and permits a smaller set of anti-tags and higher multiplexing in universal array, bead, or tag assays. The specification also describes enzymatic synthesis of UNA polynucleotides via polymerase extension using modified nucleoside triphosphates.

Independent claims

⚠️ Important caveat — no authoritative claim text was retrievable in my searches. The full patent text I was provided contains the specification and abstract but not the claims section, and the live search snippets (Google Patents, Justia, etc.) likewise did not surface the verbatim claim language. I will therefore not fabricate claim-by-claim language. Based only on the specification's summary of the invention, the patent appears to provide claims directed to at least:

1. A system comprising a first plurality of anti-tag probes comprising unstructured nucleotides (reduced ability to hybridize to other UNA-containing complements) and a second plurality of intermediary nucleic acid molecules each having a tag region (complementary to an anti-tag) and an anti-target region (complementary to a target, comprising unstructured nucleotides) — reducing cross-hybridization between anti-target and anti-tag sequences;
2. A method of assaying target nucleic acid molecules with reduced background signal/enhanced sensitivity (contacting target, intermediary molecules, and anti-tags; hybridizing; detecting); and possibly
3. A kit for such assays.

Please treat that categorization as provisional — the exact scope, number, and wording of the independent claims could not be verified from available sources.

CAFC / litigation docket check

Searches of CAFC dockets for 2026 using the exact identifier 7371580 (and variants "7,371,580," combined with "Agilent," "unstructured nucleic acids," "infringement," and "appeal") returned no results. I found no publicly indexed CAFC 2026 appeal or district-court/PTAB proceeding tied to this patent number. Given the patent's expired status (2022) and its age, this negative result is unsurprising, but it is a negative finding from my searches only — I cannot rule out a docket not indexed by the search tools I used. If you need certainty on pending litigation, I'd recommend checking the USPTO Patent Center/PTAB docket search and the CAFC's own e-Docket system directly (the CAFC public docket search was not directly accessible to me in this session).

Other points of uncertainty

• The claims text (item above) is the main gap; it should be pulled from USPTO Patent Center or Google Patents' "Claims" tab for authoritative language.
• Google Patents' assignee field is flagged as potentially inaccurate; the record shows assignment to Agilent Technologies, Inc. (recorded May 7, 2002), which I treat as reliable.
• One third-party page (wiki.golden.com) lists only two inventor names in its table, but the USPTO record and Google Patents both list all three: Yakhini, Sampson, and Myerson — I rely on the USPTO/Google Patents listing.

Based on my searches of litigation-focused databases and general web sources, I found no known litigation involving US Patent 7,371,580 as of today's date (April 26, 2026).

Search Results Summary

The searches I performed returned only non-litigation references to the patent:

1. WO2010021702A1 (patents.google.com) — Cites US Patent 7371580 as background literature regarding "binding properties" of certain nucleotides. This is a scientific/technical citation, not a court proceeding.

2. US Patent 10,384,189 and US Patent 11,407,837 (patents.justia.com) — Both list 7371580 ("Yakhini et al., May 13, 2008") in their prior-art citation fields. Again, these are patent-examination citations, not litigation.

3. A search for docket/PACER/defendant/plaintiff terms combined with the patent number returned no results, and a site-restricted search of Unified Patents' litigation portal returned nothing.

Conclusion

No litigation involving US Patent 7,371,580 is known.

Important caveats:

• The patent is assigned to Agilent Technologies Inc. and expired from its statutory term (adjusted expiration listed as November 17, 2022, status "Expired - Lifetime").
• An expired patent can still be litigated for pre-expiration damages within the statute of limitations, but I found no evidence of any such suit.
• My searches covered general web, Google Patents, Justia, and a Unified Patents portal query. I did not directly access PACER or the full CAFC opinion database (which require separate access), so the absence of results is strong but not an absolute guarantee that no case exists in a non-indexed forum. If you need absolute certainty, a paid docket search (PACER, DocketNavigator, or LexisNexis/Reuters CourtLink) against the patent number would be the definitive next step.

Proceedings overview

Zero AIA trial proceedings on file. The USPTO Open Data Portal returns no IPR/PGR/CBM cases for US 7371580, and independent web searching (USPTO PTAB, Google Patents, FreePatentsOnline, Justia, golden.com, PTACTS) surfaced no petition, institution decision, settlement, or Federal Circuit appeal referencing this patent. There is nothing to rank by impact — no claims have been invalidated, sustained, or settled through the PTAB, and no institution has ever been denied. Bottom line for a defendant: the PTAB record is a blank slate — but that is almost beside the point, because the patent expired on 2022-11-17 (status: "Expired – Lifetime") and is no longer enforceable. No proceeding-specific sections follow because there are no proceedings to report; the strategic picture is set out below.

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Strategic summary

Claims: CANCELED vs. SUSTAINED vs. UNTESTED. Every claim of US 7371580 is UNTESTED in AIA trial proceedings. No IPR, PGR, or CBM petition has ever been filed, so no claim has been canceled and no claim has been sustained by a PTAB Final Written Decision. The claims remain exactly as granted on 2008-05-13 — but that is a purely academic point, because the statutory term has run.

The controlling fact is expiration, not PTAB. Per the USPTO/Google Patents legal-status record, US 7371580 was "Expired – Lifetime" with an adjusted expiration date of 2022-11-17 — more than three years before today's date (2026-09-05). A patent that has expired cannot support an injunction, and infringement damages cease at expiration (35 U.S.C. § 154; see generally Brulotte-style post-expiration enforcement limits). If a demand letter cites this patent today, the most powerful response is not prior art — it is that the patent is dead by operation of law. This also explains the absence of PTAB activity: there was no economic incentive for a defendant or a defensive aggregator (no Unified Patents, RPX, or other challenger appears anywhere in the search results) to spend IPR costs on a patent already nearing or past its natural end.

Estoppel landscape — § 315(e)(2). Because no IPR/PGR was ever instituted, no § 315(e)(2) estoppel exists against anyone. No petitioner is barred from raising any ground, and no prior-art ground has been "used up." If the patent were somehow still relevant (it is not, post-expiration), every § 102/§ 103 ground — including art never vetted in any tribunal — would remain fully available to any defendant. The search also surfaced related Agilent UNA-family applications (e.g., US 2004/0086880, US 2002/0197618) and the sibling publication US 2003/0211474 A1 — a reminder that while this patent is expired, Agilent's broader "unstructured nucleic acid" portfolio may contain other still-in-force members worth checking by family tree before assuming the whole technology space is clear.

Pattern signals. No repeat petitioner, no patent-owner PTAB advocacy pattern, and no defensive-aggregator involvement — because there has never been a proceeding. The single meaningful signal is the patent's maintenance history: "Expired – Lifetime" rather than "Expired – Fee Related" indicates the patent ran to the end of its adjusted term rather than being abandoned for non-payment, and the ~15-month term adjustment (filed 2001-08-24; 20-year baseline 2021-08-24; adjusted expiry 2022-11-17) is consistent with ordinary PTO prosecution delay.

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Recommended next steps

• Lead with expiration. If you are a defendant facing assertion of US 7371580, your first affirmative defense is that the patent expired 2022-11-17 — confirmed on the USPTO assignment/status record and on Google Patents (https://patents.google.com/patent/US7371580/en, "Legal status: Expired – Lifetime"). No post-expiration damages or injunctive relief are available. If the demand seeks royalties for post-expiration conduct, that is a legal nullity.
• Confirm the exact expiration basis before litigating. Pull the USPTO Patent Center / Patent Term Extension records for US 09/938,937 to verify the 2022-11-17 adjusted expiration and confirm no terminal-disclaimer or reissue complications exist. If the letter asserts pre-expiration conduct, the statute of limitations on damages (35 U.S.C. § 286, six years) also cuts off anything before late 2016 — worth checking against the alleged acts.
• Do not file an IPR on this patent. With the patent expired, the PTAB would have no viable purpose: there are no prospective damages to estop and no injunction to dissolve, and the Board generally declines to expend resources where the patent can no longer be enforced. Any counsel proposing an IPR here should be challenged on strategy.
• Watch the sibling portfolio. No PTAB activity exists on the '580 patent, but related Agilent applications/publications in the UNA family (e.g., US 2004/0086880 A1, US 2002/0197618 A1, US 2003/0211474 A1) may have later-issued, still-in-force counterparts. Run a full family and maintenance-fee screen before concluding the entire technology space is free to practice.
• If the goal is a global license defense, pivot to validity on paper. Because no estoppel attaches anywhere, a defendant who needs leverage in a broader Agilent portfolio negotiation can still assemble § 102/§ 103 challenges to the UNA claims using the pre-2001 art (e.g., the Gamper, Woo, Ben-Dor, and Southern references cited in the specification) without any PTAB filter — but the cleanest and cheapest answer to a demand on this patent remains: it expired in 2022; there is nothing to license.

No PTAB proceeding exists — I am stating that plainly rather than filling the space with speculation. The USPTO ODP record is empty, and my web searches confirmed no older or recently-filed IPR/PGR/CBM that ODP has not yet indexed. The absence of PTAB activity is itself the signal: this is an expired Agilent patent that never attracted a single AIA challenge.

Based on the available records, here is the ownership-chain reconstruction for US 7371580 B2.

Note on verification limits: Live queries of the USPTO Assignment Center (assignmentcenter.uspto.gov / assignment.uspto.gov) and the RPX/Unified Patents directories could not be completed within this session. The findings below rest on the Google Patents legal-event feed (which mirrors the recorded USPTO assignment index), the authoritative patent text provided, and public corporate records. No reel/frame numbers could be independently confirmed from a live USPTO query, and none are fabricated here.

Inventors

Pattern: All three were Agilent employees at filing; no evidence of mass departure or portfolio fire-sale around the filing date.

Original assignee

• Agilent Technologies, Inc. (named on the issued patent and as assignee in the recorded original assignment).
• Line of business: diversified life-sciences, diagnostics and applied-chemicals instrumentation company (NYSE: A); its genomics business has sold DNA microarray products and consumables since the early 2000s.
• Whether Agilent ever shipped a product embodying the UNA/unstructured-nucleic-acid claims of this specific patent is unclear — the UNA (2-aminoadenosine / 2-thiothymidine / inosine / pyrrolo-pyrimidine) chemistry described here was largely research-stage at Agilent Labs, and no commercial UNA-based universal-array product could be confirmed.
• Current status: Operating (publicly traded, still active in genomics instruments and arrays). This patent, however, is expired (status "Expired – Lifetime," adjusted expiration 2022-11-17).

Assignment timeline

Per the Google Patents legal-event record (indexed from USPTO assignment data), the only conveyance of record is the original assignment from the inventors to Agilent:

• 2002-05-07 (recorded; execution date not separately shown in the indexed record) — Reel/frame not retrievable in this session; do not rely on an unverified number
  • Conveyance: Assignment of Assignors' Interest ("ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS)")
  • Assignor: Joel Myerson; Jeffrey R. Sampson; Zohar Yakhini
  • Assignee: Agilent Technologies, Inc.
  • Correspondent: Not disclosed in the indexed legal-event feed; cannot be verified. (No recurrence signal assessable.)
  • Context: Routine original assignment from employee-inventors to their employer at filing.

No post-issuance assignments, mergers, security agreements, name changes, or releases appear in the indexed record. The chain of title appears to have remained at Agilent Technologies, Inc. for the life of the patent, which then expired at term (adjusted expiration 2022-11-17).

If you can run the USPTO Assignment Center search yourself (https://assignmentcenter.uspto.gov/ — patent number 7371580 or application 09/938,937), you should see only the single 2002 conveyance described above; please treat that live query as authoritative over this reconstruction.

Timeline diagram

timeline
    title Ownership of US 7371580
    2001 : Filed by Agilent Technologies
    2002 : Inventors assign to Agilent
    2008 : Patent granted
    2022 : Patent expired

NPE / troll-pattern signals

1. Shell-entity transfer — not present. No transfer from Agilent to any LLC, "IP Holdings," licensing, or registered-agent entity appears in the indexed record.
2. Known asserter in the chain — not present. The only assignee is Agilent Technologies, Inc., an operating company, not an entity on Acacia/Marathon/IV/RPX/Unified Patents asserter lists.
3. Repeat correspondent across the chain — not present / unassessable. Only one conveyance exists; no correspondent recurrence can be evaluated from the available record.
4. Cascading transfers — not present. No chain of chained LLC assignments exists.
5. Pre-litigation transfer — not present. No assignment dated within six months of any infringement suit exists; no assertion litigation naming this patent was identified.
6. Bankruptcy fire-sale — not present. Agilent never sold this patent in bankruptcy.
7. Privateering — not present. No transfer to an NPE asserting on Agilent's behalf is recorded or reported.
8. Defensive aggregator (anti-NPE) — not present. No transfer to RPX, AST, LOT, Unified Patents, or OIN. The patent was instead neutralized by natural expiration (2022-11-17), not by aggregation.

Verdict

Insufficient data

Only the original 2002 assignment from the three inventors to Agilent Technologies, Inc. is of record, and no downstream chain, shell-entity transfer, litigation transfer, or defensive-aggregator acquisition exists in the indexed data. The most probable reading is that Agilent — an operating company — owned this patent for its entire life and never asserted it, but because the USPTO reel/frame entries and correspondent details could not be verified live in this session, and no commercial embodiment could be confirmed, the evidence supports a plain "no NPE activity observed" conclusion rather than a high-confidence classification. Verification link: https://assignmentcenter.uspto.gov/ (search patent number 7371580).

I'll research the prior-art citations for US 7371580. Let me run several targeted searches.

Let me pull the actual front-page citation lists from the patent databases.

Prior Art Analysis — US Patent 7,371,580 ("Use of unstructured nucleic acids in assaying nucleic acid molecules")

Scope note: Every identifier below was searched and interpreted literally as US 7,371,580 B2 / application 09/938,937 (Agilent Technologies; filed 2001-08-24; granted 2008-05-13). Near-match numbers surfaced by the search engine were discarded and are not reported here.

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1. Verification status of the citation lists (read first)

I could not retrieve the complete face-of-patent "(56) References Cited" section for 7371580. Specifically:

• The full patent text provided to me (authoritative per instructions) contains the abstract, description, classifications, and legal events — but not the front-page (56) citation block and not the claims.
• A direct Google Patents "Citations" scrape did not return the reference list (the indexed snippet returned only description text).
• The only front-page-style citation list I was able to retrieve comes from Justia's page for 7371580 (https://patents.justia.com/patent/7371580), reproduced in Section 2. That retrieval appears possibly incomplete (only six documents, with a bare gap between 1993 and 2000 — unusually sparse for a patent with a ~7-year prosecution), and it contains a date-inconsistency I flag explicitly in Section 4.2. Treat Section 2 as provisional pending a USPTO Patent Center / Google Patents file-wrapper pull.

By contrast, the references cited inside the 7371580 specification itself (Section 3) are taken from the full patent text supplied to me and are therefore reliable as citations contained in the patent, even though I cannot confirm which of them also appear on the printed front page.

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2. Documents cited on the face of US 7,371,580 (as retrieved)

Other (non-patent) references listed: Ben-Dor et al., J. Comput. Biol. 7(3/4), 2000; Wang et al., Science 280:1077–1082 (1998); Chee et al., Science 274:610–614 (1996); Blanchard & Hood, Nat. Biotechnol. 14:1649 (1996); DeRisi et al., Science 278:680–686 (1997); Pease et al., PNAS 91:5022–5026 (1994).

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3. References cited within the 7,371,580 specification (from the provided full text)

These are quoted/incorporated in the description and are reliable citations, though I cannot confirm which appear on the printed front page:

Patent documents expressly named in the description:

• U.S. Pat. No. 5,847,105 and WO 95/25116 — in situ synthesis of oligonucleotide probe arrays.
• U.S. Pat. Nos. 5,424,186; 5,445,934; 6,022,963 — photocleavable protecting groups for in situ array synthesis.
• U.S. Pat. No. 5,908,926 — 5′→3′ in-situ synthesis using 3′-photoremovable protecting groups.
• U.S. Pat. No. 5,948,902 — peptide nucleic acids (PNA).
• U.S. Pat. No. 5,508,178 — labels / reporter molecules / signal-producing systems.
• Sampson, U.S. Ser. No. 09/358,141 — expressly incorporated by reference; "teaches the enzymatic synthesis of UNAs using modified nucleotides and DNA polymerases."
• Others cited only in truncated run-on text in the fetched copy (the text breaks mid-sentence at "U.S. Pat. Nos." more than once), so I will not guess at those numbers.

Non-patent literature expressly named: Ben-Dor et al. (2000); Chee et al. (1996); Shalon/Solas et al., PNAS 91:5022–5026 (1994); Blanchard & Hood (1996); DeRisi et al. (1997); Wang et al., Science 280:1077–1082; Perou et al. (1999); Golub et al. (1999); Bittner et al. (2000); Pastinen et al., Genome Res. 7:606–614 (1997); Ross et al., Nat. Biotechnol. 16:1347–1351 (1998); Hacia, Nat. Genet. 21:42–47 (1999); Guo et al., NAR 22:5456–65 (1994); Maskos & Southern, NAR 20:1679–84 (1992); Southern et al., NAR 22:1368–73 (1994); Schena et al., Science 270:467–70 (1995); Strother et al., NAR 28(18):3535–3541 (2000); Zammatteo et al., Anal. Biochem. 280(1):143–150 (2000); Beier et al., NAR 27(9):1970–1977 (1999); O'Donnell et al., Anal. Chem. 69(13):2438–2443 (1997); Beaucage et al. (1981); Matteucci et al. (1981); Caruthers et al. (1987); Narang et al. (1979); Garegg et al. (1985); Brown & Brown (1991); Messing (1983); Sambrook et al. (1989); Agrawal (1999); Zon et al. (1991); and the modified-base hybridization work cited only as "Gampers et al. (supra)" and "Woo et al. (supra)."

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4. Reference-by-reference analysis

A1 — US 5,200,313 (Carrico), granted 1993-04-06

• Full citation: U.S. Patent 5,200,313, "nucleic acid hybridization assay" (Carrico), issued April 6, 1993.
• Description: A detection/hybridization-assay patent of the early-1990s sandwich-hybridization generation. I could not verify the exact title/abstract text in this session — I am characterizing it by its citation context (a hybridization-assay reference cited for general background on hybridizing labeled nucleic acids to probes).
• § 102 analysis: Does not anticipate any claim. The claims of 7,371,580 (as reflected in the specification: anti-tag probes and anti-target regions comprising unstructured nucleotides whose UNA↔UNA pairing is destabilized) require modified-base chemistry that this 1993 reference does not disclose. It is background art at most, and adds nothing to a § 103 combination.
• Caveat: Description unverified. Verify at https://patents.google.com/patent/[US5200313A](/patent/US5200313A)/en.

A2 — US 6,077,674 (Schleifer et al.), granted 2000-06-20

• Full citation: U.S. Patent 6,077,674, Schleifer et al., issued June 20, 2000.
• Description: Cited in the array-fabrication/array-chemistry lineage; consistent with Agilent/Hewlett-Packard array-manufacturing art of that period. I could not verify the exact title or abstract in this session.
• § 102 analysis: Pre-filing, so § 102(b) art is available — but on the subject matter I can attribute to it (array fabrication/use), it does not disclose: (i) anti-tag probes comprising unstructured nucleotides; (ii) intermediary molecules with a tag region plus a UNA-comprising anti-target region; or (iii) the asymmetric two-alphabet architecture that defeats anti-tag/anti-target cross-hybridization. No anticipation of any claim. Relevant only as evidence that array platforms were known.
• Caveat: Verify at https://patents.google.com/patent/[US6077674A](/patent/US6077674A)/en.

A3 — US 6,428,957 (Delenstarr), granted 2002-08-06

• Full citation: U.S. Patent 6,428,957, Delenstarr, issued August 6, 2002 (Agilent).
• Description: Agilent nucleic-acid-array-related subject matter (title unverified in this session). Because it issued after the 2001-08-24 filing, it is not § 102(a)/(b) art; it could only be § 102(e) art if its U.S. filing date predates 2001-08-24, and if commonly owned with 7,371,580 by Agilent, it would be disqualifiable for § 103 purposes under pre-AIA § 103(c).
• § 102 analysis: No anticipation on the record available; its subject matter is array methodology, not unstructured nucleic acids.

A4 — US 7,052,841 (Delenstarr), granted 2006-05-30 — ⚠️ see flag

• § 102 analysis: On its face cannot be § 102(a)/(b) art (granted 2006, five years after the filing). No anticipation.

A5 — US 2006/0246494 A1 (Delenstarr), published 2006-11-02 — ⚠️ see flag

• § 102 analysis: On its face cannot be § 102(a)/(b) art. At most it could be § 102(e) art through an earlier effective U.S. filing date, and even then § 103(c) common-ownership disqualification is likely. No anticipation.

4.2 ⚠️ Explicit contradiction flag

The retrieved Justia list places US 7,052,841 (2006-05-30) and US 2006/0246494 (2006-11-02) in the "Referenced Cited / U.S. Patent Documents" block of a patent filed 2001-08-24. Those two documents cannot be § 102(a) or § 102(b) prior art against that filing date. Two possible explanations, and I cannot resolve which is correct from the sources available:

1. They were cited by the examiner late in the long ~7-year prosecution (possible on timing), but only as § 102(e) art or as background — not as § 102(a)/(b) art; or
2. The Justia block I retrieved mixes front-page (56) references with other citation data, so the list is not a clean face-of-patent record.

Either way, do not treat A4/A5 as § 102(a)/(b) prior art, and verify the actual front-page list before relying on this table.

A6 — EP 1 072 679 (A2/A3), published January 2001 — the single most relevant citation retrieved

• Full citation: European Patent Application EP 1 072 679 A2/A3 (Agilent Technologies; Sampson), published January 2001; counterpart of U.S. Ser. No. 09/358,141 (filed 1999-07-20), "Nucleic acid molecules with reduced secondary structure" (the "UNAs" application). Corroborating publications: US 2005/0032053 A1 (divisional of 09/358,141) and US 2002/0197618 A1.
• Description: Defines "unstructured nucleic acids" (UNAs) exactly as 7,371,580 uses the term — nucleic acid molecules with reduced intramolecular secondary structure, whose complementary sequence elements do not form stable base pairs, but which "retain the ability to form intermolecular hydrogen bond base pairs with other nucleic acid molecules." It expressly recites the 2-aminoadenosine (D) / 2-thiothymidine (2-thioT), inosine (I) / pyrrolo-pyrimidine (P), and 2-thiocytidine / G analog systems, teaches enzymatic synthesis by polymerase and the corresponding triphosphates (dDTP, 2-thioTTP, dITP, dPTP), and lists applications including nucleic acid arrays, ligase assays and polymerase extension assays.
• § 102 analysis — claim-by-claim:
  • The system claim(s) (anti-tag plurality + intermediary plurality with tag region and UNA-comprising anti-target region) — NOT anticipated. EP 1 072 679 discloses UNA composition and synthesis, and gestures at array use, but it does not disclose the universal tag/anti-tag architecture: it does not disclose a first plurality of spatially addressable anti-tag probes whose cognate tags are non-UNA, nor the deliberate assignment of a UNA alphabet to the anti-target domain precisely so it cannot cross-react with a UNA anti-tag. The "two non-interacting alphabets" limitation is present only in 7,371,580.
  • Dependent claims reciting specific analog pairs (D/2-thioT; I/P; 2-thioC/G) — these are the closest thing to anticipation in this record, because EP 1 072 679 names the same nucleotide species. But even here, anticipation requires that the reference disclose the claimed combination as arranged in the claim (i.e., those bases within an anti-tag/anti-target assay system). If any dependent claim is drafted narrowly to "an anti-tag probe comprising 2-aminoadenosine and 2-thiothymidine," EP 1 072 679 is a serious § 102 threat; if the claim requires the assay context, it is not.
  • Method and kit claims — NOT anticipated, for the same reason: the reference teaches UNA-making and general array use, not the two-step tag/anti-tag assay flow.
• Bottom line for A6: EP 1 072 679 is almost certainly the reference the examiner used, and it is the strongest § 103 reference in the record (see the Obviousness section already generated, Ground 1). It is not a clean § 102 anticipation of the independent claims.

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5. Non-patent references: § 102 relevance

• Ben-Dor, Karp, Schwikowski & Yakhini, "Universal DNA tag systems: a combinatorial design scheme," J. Comput. Biol. 7(3-4):503–519 (2000) — supplies the tag/anti-tag universal-array architecture and frames cross-hybridization as the limiting error. No anticipation (no UNA disclosure), but it is the essential motivation-to-combine reference for § 103.
• Wang et al. (1998), Chee et al. (1996), Blanchard & Hood (1996), DeRisi et al. (1997), Pease et al. (1994) — high-density array/hybridization background. No anticipation; minimal § 103 weight beyond establishing that array hybridization assays were routine.
• "Gampers et al." and "Woo et al." — per 7,371,580's own text, these taught chemical synthesis of complementary oligonucleotides containing modified nucleotides and demonstrated reduced hybridization between modified complements. As cited, they support obviousness of specific analog pairs, but I could not verify these two references (apparent typographical renderings) in this session; retrieve the actual citations from the patent's own reference list.

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6. Forward citations (patents citing 7,371,580) — not prior art

Surfaced by search and listed only to avoid confusion; all post-date the 2001 filing and therefore cannot anticipate:

• WO 2010/021702 A1 (cites 7371580 as teaching only "binding properties")
• US 10,170,840; US 10,894,242; US 11,484,915; US 11,407,837; US 10,316,352; US 10,829,801; US 12,065,693 (Google Patents "cited by")
• EP 3 227 447 B1 (cites US 7371580 B at [0014]); CN 107250148 B (cites US7371580 for the definition of "UNA")

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7. Conclusion — most relevant prior art and § 102 posture

Answer to the § 102 question: No reference cited by or in US 7,371,580 anticipates its independent claims. The claim scope turns on the asymmetric two-alphabet architecture (UNA anti-tag ↔ non-UNA tag; UNA anti-target ↔ natural target), which no single cited reference discloses. The realistic risk to these claims is § 103, led by EP 1 072 679 in view of Ben-Dor et al. (2000) — consistent with the Obviousness section already generated.

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8. Open items / recommended verification

1. Pull the authoritative (56) list from USPTO Patent Center (application 09/938,937) or the Google Patents "Citations" tab. My Section 2 list is from a third-party page and may be incomplete (the 1993→2000 gap is suspicious) — and it conflicts with the description's own citations to US 5,847,105, 5,424,186, 5,445,934, 6,022,963, 5,908,926, 5,948,902 and 5,508,178, which do not appear in the retrieved Section 2 list.
2. Verify A1–A5 titles/abstracts, which I flagged as unverified rather than guessed.
3. Flagged contradiction (restated): the presence of two 2006 documents in a "references cited" block for a 2001-filed patent is temporally impossible as § 102(a)/(b) art; resolve whether the Justia block conflates sources.
4. Minor discrepancy, already noted in the earlier summary section: wiki.golden.com shows application number "099389370" (ten digits) whereas the authoritative number is 09/938,937; and that page's table shows only some inventor names. Neither changes the identity of the patent.

Obviousness Analysis — U.S. Patent 7,371,580 ("Use of unstructured nucleic acids in assaying nucleic acid molecules")

Preliminary notes and scope limitations

• No "Prior Art section" was included in the materials provided to me. The fetched Google Patents text contains the abstract, description, and classification data but not the formal "References Cited" (prior-art) portion or the claims text. The prior-art analysis below therefore reconstructs the closest prior-art landscape from (a) references affirmatively cited in the patent's own description, and (b) independent web-verified references, per the operating rule that search results are ground truth where they conflict with training data.
• Because the claim language was not reproduced in the provided text, I analyze the claims as reflected in the specification's "Summary" and figure descriptions (system claims directed to UNA-containing anti-tag probes plus intermediary molecules having a "tag" first region and a UNA-containing "anti-target" second region; method claims for two-step target/tag hybridization; kit claims). The analysis should be validated against the exact claim text before use in any proceeding.
• This is a technical analysis under 35 U.S.C. § 103, not legal advice.

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1. Claimed invention in brief

As disclosed, the invention solves a specific problem in universal (fixed) tag/anti-tag array assays (e.g., SNP genotyping, expression profiling). In such assays, each "intermediary" nucleic acid has:

1. a tag region that hybridizes to a spatially addressed anti-tag probe on the array, and
2. an anti-target region that hybridizes to the biological target to be assayed.

The patent identifies a previously unaddressed cross-hybridization failure mode: anti-target regions of intermediary molecules can cross-hybridize to anti-tag probes on the array (Fig. 1B), consuming both probes and intermediaries and limiting multiplexing. The invention's solution is to build the anti-tag probes and the anti-target regions from "unstructured nucleotides" (UNAs) — modified bases such that UNA↔UNA base pairs are destabilized, while UNA↔natural-complement pairs remain functional. Thus anti-target (UNA) cannot stick to anti-tag (UNA), but each still hybridizes to its natural cognate (target; tag). Specific analog pairs disclosed are 2-aminoadenosine (D)/2-thiothymidine (2-thioT) and inosine (I)/pyrrolo-pyrimidine (P) (and a 2-thiocytidine/G variant), with FIG. 3 rationalizing why D/2-thioT and I/P pairs form only one hydrogen bond or suffer steric clash.

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2. Person of ordinary skill in the art (POSITA)

A POSITA circa August 2001 would be a molecular biologist or nucleic-acid chemist with 3–5 years' experience in hybridization-based assays, microarray probe/tag-set design, and modified-nucleotide chemistry — i.e., someone conversant with both the universal-array literature (Ben-Dor et al.) and the modified-base literature (2-aminoadenosine, 2-thiothymidine, inosine, pyrrolo-pyrimidine).

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3. Key prior-art references (dates verified where possible)

URLs verified during this analysis: Ben-Dor (https://journals.sagepub.com/doi/abs/10.1089/106652700750050916; https://dl.acm.org/doi/abs/10.1145/[332306](/patent/332306).[332346](/patent/332346)); EP 1 072 679 (https://pubchem.ncbi.nlm.nih.gov/patent/EP-[1072679](/patent/1072679)-A3 and https://patents.google.com/patent/EP1072679A2); US 7,371,580 and its family member EP 1 288 313 B1 (https://patents.google.com/patent/EP1288313B1/en); US 2002/0197618 A1 (https://patents.google.com/patent/JP2013532494A5/...); WO 2010/021702 A1 (https://patents.google.com/patent/WO2010021702A1).

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4. Primary § 103 combination

Ground 1 — Sampson (UNAs) in view of Ben-Dor (universal tag/anti-tag arrays) → system claims

Claim element map (inferred from the specification):

Why a POSITA would combine them:

• Ben-Dor supplies the reason to want orthogonal hybridization: the entire paper is an exercise in minimizing unintended probe–probe cross-hybridization in universal arrays, and it explicitly notes that "minimizing experimental errors caused by cross-hybridization" is the design goal.
• Sampson supplies the mechanism: a complete, enabled alphabet of modified bases in which two UNA molecules with complementary sequences form only ~1 hydrogen bond per pair (or sterically clash) and therefore do not stably duplex, while the same UNA strand hybridizes to a natural or differently-modified complement.
• A POSITA facing Ben-Dor's anti-tag/anti-target cross-talk problem, and knowing Sampson's UNA chemistry, would immediately recognize that assigning the UNA alphabet to the two non-cognate partners (anti-tag and anti-target) converts a thermodynamic design problem (sequence screening, as in Ben-Dor) into an orthogonal-alphabet problem — with the obvious, finite, predictable solution of substituting D/2-thioT (or I/P) for A/T (or G/C) in those two domains. The tag region and natural target, which must hybridize to the UNA probes, would correspondingly be built from the natural complements, exactly as Sampson teaches that UNAs "retain the ability to form intermolecular hydrogen bond base pairs with other nucleic acid molecules" that are not UNAs.
• No unexpected result: Sampson already demonstrated both halves of the required behavior (reduced UNA-UNA duplexing and preserved UNA-natural duplexing) and demonstrated enzymatic synthesis of kilobase-scale UNAs, so implementation in an array assay required routine optimization only.

Ground 2 — Sampson + Ben-Dor + Woo/Gamper modified-base literature → dependent claims reciting specific analog pairs

The dependent-claim features reciting 2-aminoadenosine/2-thiothymidine and inosine/pyrrolo-pyrimidine (and the 2-thiocytidine variant) are the very nucleotide pairs named in Sampson's EP 1 072 679 disclosure, and the Woo/Gamper references cited in the patent itself are said by the specification to "teach the chemical synthesis of complementary oligonucleotides containing modified nucleotides and demonstrate … a reduced ability to hybridize to each other." Each analog pair's pairing geometry (D/2-thioT steric clash; I/P single hydrogen bond; FIG. 3 of the patent) was thus known and published. Selecting those exact bases for the UNA domains of Ground 1 is an obvious design choice with a documented rationale in the prior art; no claim based solely on the identity of the analog pair adds patentable weight.

Ground 3 — Sampson + universal tag-array literature → method and kit claims

The method claims (contacting a sample with intermediaries whose UNA-containing anti-target regions hybridize to natural targets; hybridizing tag regions to UNA anti-tags; optionally in two steps) merely sequence the two hybridizations that Ben-Dor (2000) and the zip-code literature already performed, substituting the UNA alphabet taught by Sampson. The patent itself states the two-step format is known ("Ben-Dor et al. supra"). Kit claims (UNA anti-tag array + UNA intermediaries) are the commoditized packaging of the same combination.

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5. Motivation-to-combine analysis under the Graham framework

1. Scope and content of prior art: Ben-Dor and the universal-array art establish the tag/anti-tag architecture and the paramount importance of suppressing cross-hybridization. Sampson establishes an enabled UNA alphabet with exactly the orthogonal hybridization properties needed.
2. Differences: Over Ben-Dor alone — the use of UNAs in the anti-tag and anti-target domains. Over Sampson alone — the specific application to a two-domain universal-array assay. Each reference supplies what the other lacks; the combination is a textbook "known technique (UNA chemistry) applied to a known problem (array cross-hybridization) with a predictable result" (KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007)).
3. Level of ordinary skill: As defined above, a POSITA would straddle both fields.
4. Secondary considerations: No litigation is known (per the prior analysis section), which eliminates a jury finding of long-felt need being resolved by this patent in litigation. The concept of "self-avoiding" modified-base systems was already in the air (see WO 2010/021702, which treats 7,371,580 as merely confirming "binding properties"), and later SAMRS-type work built directly on this same modified-base idea — evidence the field regarded the underlying base chemistry, not the assay architecture, as the enabling insight.

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6. Strongest counterarguments (claims that may survive)

• Combination of both UNA domains. Sampson's examples address reducing secondary structure within a single UNA and cross-hybridization between two UNA molecules generally. The specific insight of 737,1580 — that in a two-domain assay the anti-tag and anti-target should share a UNA alphabet so they cannot cross-react, while the tag (anti-tag's cognate) must be natural — requires recognizing that the tag/anti-tag pair and the anti-target/target pair must use different, non-interacting alphabets. If the claims require that specific architecture (rather than merely "UNA probes"), a defendant would need Ben-Dor + Sampson + a reason to assign alphabets asymmetrically; an argument of "teaching away" (Sampson is about reducing self-structure, not about multiplexed assay orthogonalization) could be raised.
• Anti-target UNA ↔ natural target hybridization at assay stringency. Sampson demonstrates UNA/natural duplexing in polymerase extension and hybridization contexts, but a challenger must show that UNA-containing anti-targets retain adequate sensitivity to complex biological targets under array wash stringencies — an empirical question the patent itself addressed with data (FIGS. 4–9).
• Ben-Dor is co-authored by Yakhini (a 737,1580 inventor) — this does not remove it as §102(a)/(b) art, but the common-assignee relationship with Sampson's UNA application could support an inventorship/priority argument that the combination was made by the same team, which cuts against characterizing the combination as obvious but also complicates any §103(c) disqualification analysis (which under the pre-AIA statute as in force in 2001 reaches only §102(e)/(f)/(g) art, not §102(a) publications).

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7. Conclusion

On the available record, independent system claims would most likely be vulnerable under § 103 as an obvious combination of Sampson's UNA alphabet (incorporated by reference into the patent and published before the filing date as EP 1 072 679) with Ben-Dor's universal tag-array architecture. The most defensible claims would be those requiring the full asymmetric two-alphabet architecture, where a non-obviousness argument based on the absence of an explicit motivation in either reference is strongest.

Caveats: This analysis is based on the specification and web-verified references because the formal Prior Art/References-Cited page and the claims text were not included in the materials provided. Before relying on it in any opinion or proceeding, the exact claim language and the file-wrapper "References Cited" list for US 7,371,580 should be retrieved and mapped element-by-element.