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.

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.

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 US Patent 7,371,580 and its cited prior art references. Let me search for the patent's bibliographic data and citation information.

Let me search for the specific citation list on the patent's front page and in USPTO records.

I need the examiner-cited references printed on the patent's front page. Let me look at the Google Patents citation page and USPTO records more directly.

Identification of the patent

The searched patent is US 7,371,580 B2 — "Use of unstructured nucleic acids in assaying nucleic acid molecules." I confirmed the number is literal (not 7,371,580D, not a foreign-family equivalent such as EP 1 288 313 B1 or DE 602 08 278 T2, which are related family members, not the U.S. patent itself).

Important evidentiary caveat

I was not able to retrieve the complete front-page "References Cited" section (the examiner-applied U.S. patents / "Other Publications" list) from USPTO or Google Patents within the search limits. The Google Patents full-text snapshot you supplied contains the specification's description-cited references, not necessarily the complete examiner citation list. In addition, the full claims text was not present in the excerpt provided. Accordingly, my claim-level § 102 analysis below is a best-effort mapping based on (i) the claimed subject matter as described in the Abstract/Summary/Description and (ii) the references affirmatively identifiable in the patent text. Where I lack confidence, I say so rather than fabricate a claim-by-claim rejection history.

Claimed subject matter (for mapping purposes)

Based on the Abstract and Summary, the claims are directed to:

• System claims: (a) a first plurality of nucleic acid probes ("anti-tags") comprising unstructured nucleotides (UNAs) having a reduced ability to hybridize to complementary unstructured nucleotides, and (b) a second plurality of "intermediary" nucleic acid molecules each having a first tag region complementary to an anti-tag and a second anti-target region complementary to a target nucleic acid, where the anti-target region also comprises UNAs — the UNA/UNA pairing suppressing anti-tag/anti-target cross-hybridization while preserving anti-tag/tag and anti-target/target hybridization.
• Method claims: assaying/sorting/detecting target nucleic acids with reduced cross-hybridization and reduced intramolecular secondary structure.
• Kit claims.
• Specific UNA chemistries: e.g., 2-aminoadenosine (D) paired opposite natural T, 2-thiothymidine (2-thioT/S) paired opposite natural A, inosine (I) opposite C, pyrrolo-pyrimidine (P) opposite G, and the "disallowed" D/S and I/P self-pairings; enzymatic generation via modified dNTPs (dDTP, 2-thioTTP, dITP, dPTP, 2-thio-dCTP).

Prior art identifiable from the patent record

A. U.S. patents/publications referenced in the specification (most relevant)

1. Sampson, U.S. Ser. No. 09/358,141 (incorporated by reference as teaching "enzymatic synthesis of UNAs using modified nucleotides and DNA polymerases")

   • Co-pending at the filing date; if it issued/published with an earlier effective date it would be 35 U.S.C. § 102(e) art.
   • Disclosure: polymerase-mediated incorporation of the modified triphosphates (dDTP, 2-thioTTP, dITP, dPTP) into long polynucleotides.
   • § 102 relevance: reads on method claims directed to generating UNA-containing anti-targets/anti-tags enzymatically. It does not by itself disclose the two-part tag/anti-tag + anti-target assay architecture, so it would most plausibly be applied against method steps of UNA synthesis rather than the full system claim.

2. U.S. Pat. No. 5,948,902 (peptide nucleic acids / PNA; hybridize sequence-specifically)

   • 1999 issue date (prior art under § 102(a)/(b) for an Aug. 24, 2001 filing).
   • Disclosure: backbone-modified nucleic acid analogs that hybridize in a sequence-specific manner.
   • § 102 relevance: background only. PNA is not a "UNA" as defined (modified base-pair hydrogen bonding, not backbone modification). Low anticipation potential against the UNA-reciting claims; would be a secondary reference.

3. U.S. Pat. No. 5,847,105 (in situ synthesis of oligonucleotide probe arrays, per WO 95/25116)

   • 1998 issue date.
   • Disclosure: spatially addressable probe arrays made by in situ synthesis.
   • § 102 relevance: against elements reciting "anti-tag molecules immobilized on a solid support in a spatially addressable array." Does not disclose UNAs or tag/anti-target intermediates.

4. U.S. Pat. Nos. 5,424,186; 5,445,934; 6,022,963 (photocleavable protecting groups for array synthesis)

   • 1995–2000 issue dates.
   • § 102 relevance: array-manufacturing background; not anticipatory of the UNA system/method claims.

5. U.S. Pat. No. 5,908,926 (3′-photoremovable protecting groups; 5′→3′ in situ synthesis)

   • 1999 issue date.
   • § 102 relevance: same as above — probe-array construction only.

6. U.S. Pat. No. 5,508,178 (signal-producing system / labels)

   • § 102 relevance: label/detection background only; not anticipatory of the hybridizing-system claims.

7. WO 95/25116 (in situ oligonucleotide array synthesis; U.S. national-phase counterpart of the '105 patent family)

   • § 102 relevance: array background only.

B. Non-patent literature referenced in the specification (chronological)

1. Solas/Pease et al., Proc. Natl. Acad. Sci. USA 91:5022–5026 (1994) — light-directed in situ synthesis of oligonucleotide arrays; array background, not UNA disclosure.

2. Chee et al., Science 274:610–614 (1996) — high-density array hybridization; background.

3. Blanchard & Hood, Nature Biotechnology 14:1649 (1996) — array-based hybridization; background.

4. DeRisi et al., Science 278:680–686 (1997) — cDNA microarray gene-expression monitoring; background for simultaneous assays.

5. Pastinen et al., Genome Research 7:606–614 (1997) — array-based single-nucleotide primer extension/genotyping; background.

6. Ross et al., Nature Biotechnology 16:1347–1351 (1998) — multiplex genotyping with DNA arrays + mass spectrometry; background.

7. Hacia, Nature Genetics 21:42–47 (1999) — resequencing/mutational analysis with oligonucleotide arrays; background.

8. Perou et al., PNAS USA 96:9212–9217 (1999); Golub et al., Science 286:531–537 (1999); Bittner et al., Nature 406:536–540 (2000) — large-scale expression profiling using arrays; background.

9. Ben-Dor et al., J. Comput. Biol. 7(3–4):503–519 (2000) — the closest prior-art teaching of the universal tag/anti-tag architecture (design of tag and anti-tag oligonucleotide sets for universal arrays; minimizing multiple tag-to-anti-tag combinations).

   • § 102 relevance: reads on the structural backbone of the system/method claims — intermediary molecules with tag regions hybridizing to arrayed anti-tags and anti-target regions hybridizing to targets. Critically, the specification itself states that Ben-Dor "does not address the problem of cross hybridization between anti-target sequences ... and anti-tag sequences" — i.e., it lacks the UNA modification feature that is the point of novelty. Therefore it is the best single reference for the preamble/structural elements but is unlikely to fully anticipate the UNA-reciting claims.

10. Agrawal, Biochim. Biophys. Acta 1489:53–68 (1999) and Zon et al., Anticancer Drug Des. 6:539–568 (1991) — phosphorothioate backbone modifications for nuclease stability; background for backbone modification generally, not UNA base-pair chemistry.

11. Guo et al., Nucleic Acids Res. 22:5456–5465 (1994); Maskos & Southern, Nucleic Acids Res. 20:1679–1684 (1992); Southern et al., Nucleic Acids Res. 22:1368–1373 (1994); Schena et al., Science 270:467–470 (1995) — surface derivatization and immobilization of oligonucleotide arrays; substrate/probe-immobilization background.

12. Beaucage et al., Tetrahedron Lett. 22:1859 (1981); Matteucci et al., J. Am. Chem. Soc. 103:3185 (1981); Caruthers et al., Methods Enzymol. 154:287 (1987); Narang et al., Methods Enzymol. 68:90 (1979); Garegg et al., Chem. Scripta 25:280–282 (1985); Froehler (H-phosphonate) — chemical oligonucleotide synthesis methods; background.

13. Strother et al., Nucleic Acids Res. 28:3535–3541 (2000); Zammatteo et al., Anal. Biochem. 280:143–150 (2000); Beier et al., Nucleic Acids Res. 27:1970–1977 (1999); O'Donnell et al., Anal. Chem. 69:2438–2443 (1997) — covalent attachment chemistries of oligonucleotides to array surfaces; background.

14. "Gampers et al. (supra)" and "Woo et al. (supra)" — cited in the specification for chemical synthesis of complementary oligonucleotides containing modified nucleotides that show reduced ability to hybridize to each other. These are incomplete/in-line citations (no full bibliographic data given in the patent text I possess), so I cannot provide reliable full citations for them — and I flag them as "do not know with high confidence."

15. Wang et al., Science 280:1077–1082 (1998) — referenced in background for target-specific arrays (SNP detection); background.

C. Foreign/related documents (not anticipatory U.S. § 102 art)

• EP 1 288 313 B1 / EP 02 255 908 A and DE 602 08 278 T2 — family members claiming priority from the same U.S. application; not prior art against US 7,371,580.

Assessment of most relevant prior art and § 102 potential

• Highest relevance to the claimed combination: Ben-Dor et al. (2000) for the universal tag/anti-tag sorting system, combined with Sampson U.S. Ser. No. 09/358,141 for enzymatic UNA synthesis. Neither alone discloses the complete claimed system (UNAs in both anti-tag and anti-target moieties to suppress cross-hybridization), which is consistent with the claims having been allowed.
• Single-reference § 102 anticipation: I have not found any single reference in the accessible record that discloses every element of the UNA-based system/method claims (anti-tags with unstructured nucleotides + intermediary molecules with tag and UNA-containing anti-target regions + preservation of intended hybridization). The specification's own statements — that fragmentation was the prior approach to cross-hybridization and that Ben-Dor did not address anti-target/anti-tag cross-hybridization — support this.
• If you need the exact examiner-applied references and the prosecution-history § 103/§ 102 rejections, the authoritative source is the USPTO file wrapper for Application 09/938,937 (Patent Center/PAIR), which I could not fully retrieve in the searches run here. The claim-number mapping you requested is best done against that record plus the issued claims, which were not included in the excerpt provided.

Would you like me to (1) attempt retrieval of the issued claims text, or (2) pull the file-wrapper "References Cited" / Notice of References Cited from USPTO Patent Center in a fresh search round?

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.

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.

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).

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).

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.

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.

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).

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.