Invalidity dossier

US 5695940

Method of sequencing by hybridization of oligonucleotide probes

Current assignee: Hyseq, Inc.

Added 9/30/2026, 3:05:04 PM

At a glanceNo PTAB challenges1 lawsuit on fileasserted by Hyseq, Inc.Biotechnology

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Patent summary

Title, assignee, inventors, filing/issue dates, abstract, and a plain-language overview of the claims.

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US Patent 5,695,940 — Summary

Identification (as it appears in the record — no corrections applied)

Field Value
Patent number US 5,695,940 A
Title "Method of sequencing by hybridization of oligonucleotide probes"
Inventors Radoje T. Drmanac; Radomir B. Crkvenjakov
Assignee (original / current per Google Patents) Hyseq Inc
Application number US 08/460,853
Filing date June 5, 1995
Issue/publication date December 9, 1997
Priority date April 1, 1987 (priority claimed from YU 00570/87A; some databases, e.g. Unified Patents, list 1987‑03‑31)
Legal status Expired – Fee Related; anticipated expiration December 9, 2014
Continuity Continuation of Ser. No. 08/203,502 (now US 5,525,464) → file‑wrapper continuation of 08/048,152 → continuation of 07/576,559 → CIP of 07/175,088
Family members US 5,525,464; US 5,972,619; US 6,316,191 B1; US 2002/0106673 A1

Abstract (as published). The patent describes hybridization conditions under which oligonucleotide probes hybridize preferentially to entirely complementary, homologous nucleic acid targets. Under these conditions overlapping oligonucleotide probes associate with a target nucleic acid; after washes, positive hybridization signals are used to assemble the target sequence. Targets are applied as dots, and up to ~100,000 probes of the type (A,T,C,G)(A,T,C,G)N8(A,T,C,G) are used to obtain sequence information by simultaneous hybridization to filter‑bound nucleic acids. Additional conditions permit stringent hybridization of 6–10 nucleotide oligomers. A computer process determines the sequence of the target, including targets of mammalian‑genome complexity.

Independent claims — plain‑language overview

I could retrieve a three‑claim set (claims 1, 2, 3), with claims 1 and 2 independent and claim 3 depending from claim 2. The full text I was given for this patent (Google Patents) is truncated before the claims section, so this claim listing comes from a secondary reproduction (everypatent.com) rather than the authoritative source — treat the exact wording as unverified, though it is consistent with the specification's teaching of 6‑ to 10‑mer probes.

  • Claim 1 — Full sequencing method. A method of sequencing a target nucleic acid of unknown sequence, with steps: (a) using conditions that distinguish an exactly complementary probe from a probe having a single mismatched nucleotide; (b) contacting the target with a plurality of oligonucleotides each 6 to 10 nucleotides long; (c) forming duplexes with the target; (d) washing the duplexes; (e) detecting the oligonucleotides that positively hybridized; and (f) compiling the target's sequence from overlapping positively‑hybridizing oligonucleotides. The core is the combination of short (6–10mer) probes plus mismatch‑discriminating hybridization/washing conditions, followed by overlap‑based assembly.

  • Claim 2 — Partial sequencing method. A method for partial sequencing of a target: same mismatch‑discriminating condition and same contact/duplex/wash/detect steps, but the target is contacted with a subset (less than the totality) of probes of a given length, each at least six nucleotides long, and a partial sequence is compiled from those probes that duplex with the target and overlap at least one other probe. The distinction from claim 1 is the deliberate use of an incomplete probe set yielding partial rather than complete sequence.

  • Claim 3 (dependent on claim 2) — limits the probes of claim 2 to 6–10 nucleotides in length.

Litigation / docket status — important caveat

  • Historical litigation (verified): US 5,695,940 was one of the three Hyseq patents asserted against Affymetrix — the others being US 5,202,231 and US 5,525,464. U.S. District Judge Ronald M. Whyte (N.D. Cal.) issued a first Markman ruling on October 26, 1999 and a revised Markman ruling announced August 2, 2000; Affymetrix's public statement indicates the court construed "sequencing" narrowly and that Affymetrix intended to move for summary judgment. I could not confirm the ultimate disposition of the '940 patent from authoritative sources in this search. Secondary literature also describes this Hyseq–Affymetrix dispute as concerning US 5,695,940 and US 5,525,464.
  • CAFC 2026 dockets: I found no evidence of any 2026 Court of Appeals for the Federal Circuit docket activity involving US 5,695,940. This is consistent with the patent being expired since December 9, 2014 (though expired patents can still appear in Article III damages proceedings and in PTAB proceedings). I could not query PACER or CourtListener directly in this session, so this should be treated as a negative search result, not an affirmative confirmation of no activity. To be certain, verify against PACER/CM‑ECF and CourtListener dockets for US 5,695,940.

Notes on uncertainty

  • Bibliographic data (title, inventors, assignee, application number, dates, status) is from Google Patents' full‑text record and the Unified Patents portal; these agree except for a one‑day difference in the 1987 priority date (April 1 vs. March 31), which I have flagged rather than reconciled.
  • The assignee history includes a December 14, 2004 security agreement recorded to Affymetrix, Inc. and Nuvelo, Inc. (assignor Callida Genomics, Inc.), an assignment chain that post‑dates the original Hyseq ownership.
  • Claim text is from a secondary source and could not be cross‑checked against the authoritative patent document, which was truncated before the claims in the material provided.

Generated 9/30/2026, 3:11:04 PM

Cases on file (1)

Group view →

Specific litigation cases in our database that name US patent 5695940. The free-form analysis below may also discuss cases beyond this list.

Litigation summary

Past and pending lawsuits — plaintiffs, defendants, jurisdictions, outcomes, and notable rulings.

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I'll research litigation involving US patent 5,695,940. Let me search multiple sources.

Let me search for specific litigation involving the assignees (Hyseq/Affymetrix) and this patent family.

Let me dig deeper into the specific Hyseq v. Affymetrix cases and check for any other litigations.

Litigation involving U.S. Patent No. 5,695,940

Yes — U.S. 5,695,940 has been involved in litigation. It was asserted by its owner Hyseq, Inc. against Affymetrix, Inc. in the U.S. District Court for the Northern District of California (San Jose Division), as part of the Hyseq–Affymetrix "sequencing by hybridization" (SBH) patent war of the late 1990s/early 2000s.

The cases

Case Parties Jurisdiction Case No. Filed Status/Outcome
Hyseq, Inc. v. Affymetrix, Inc. Hyseq (P) v. Affymetrix (D) N.D. Cal., San Jose Div. C 97‑20188 RMW (ENE) Mar. 4, 1997 Settled; dismissed with prejudice Oct. 2001
Affymetrix, Inc. v. Hyseq, Inc. Affymetrix (P) v. Hyseq (D) N.D. Cal., San Jose Div. C 99‑21163 JF 1999 Settled; dismissed with prejudice Oct. 2001
Hyseq, Inc. v. Affymetrix, Inc. Hyseq (P/Counterdef.) v. Affymetrix (D/Countercl.) N.D. Cal., San Jose Div. C 00‑20050 RMW 2000 Settled; dismissed with prejudice Oct. 2001

Grounding

  • The '940 patent was expressly among the patents asserted. Affymetrix's Form 8‑K (Nov. 1, 2001) states that the October 24, 2001 settlement covered "all existing litigation… that began in March 1997," and that "Affymetrix and Hyseq have acknowledged the validity and enforceability of the patents asserted in these lawsuits, which are Affymetrix' U.S. Patent Nos. 5,795,716, 5,744,305 and 5,800,992 and Hyseq's U.S. Patent Nos. 5,202,231, 5,525,464, 5,695,940, 6,018,041 and 5,972,619." (https://capedge.com/filing/[913077](/patent/913077)/0000912057-01-[537335](/patent/537335)/AFFX-8K)
  • BioCentury reported that in the two 1997 suits Hyseq alleged Affymetrix infringed "U.S. Patents Nos. 5,202,231; 5,525,464; and 5,695,940," its SBH patents. (https://www.biocentury.com/article/56155/markman-clarification-in-hyseq-affymetrix-suit)
  • Nature Biotechnology (May 1997) reported Hyseq "filed a complaint on March 4 against Affymetrix… for infringement," and noted the case was headed to the "Northern District Court of California." (https://www.nature.com/articles/nbt0597-406a.pdf)
  • The three case numbers/docket identities and their dismissal are confirmed by the Affymetrix 8‑K cited above (C 97‑20188 RMW (ENE); C 99‑21163 JF; C 00‑20050 RMW).
  • The academic review Microarray technology – an intellectual property retrospective confirms the Affymetrix–Hyseq dispute "arranged a settlement in October 2001 that dismissed all pending lawsuits."
  • Google Patents flags this family as "Family has litigation" (Darts‑IP).

Important caveats

  1. Timing issue with the '940 patent. The March 4, 1997 complaint predates issuance of the '940 patent (issued Dec. 9, 1997), so the initial complaint could only have asserted '231 and '464. The '940 patent was necessarily added later (by amended complaint or in one of the follow-on suits). BioCentury's reference to "two 1997 suits" suggests a second 1997-filed action; I could not confirm the docket number of any second 1997 case, so treat that detail as unverified.
  2. No merits ruling on the '940 patent. The dispute ended by settlement (Oct. 24, 2001) with dismissal with prejudice; there was no judgment of infringement or invalidity as to '940. The well-known Markman opinion, Affymetrix, Inc. v. Hyseq, Inc., 132 F. Supp. 2d 1212 (N.D. Cal. 2001), construed Affymetrix's '716 patent, not the '940 patent.
  3. Related proceeding (not litigation): As part of the settlement, Hyseq abandoned its contest in the interference Chee v. Drmanac, Interference No. 104,552 (USPTO). This is a patent interference, not a court case, but it involves the same patent family/inventorship.
  4. Other reported "Affymetrix suits": A Korean patent document (KR101269441B1) states that US‑5695940, US‑5525464 and US‑5700637 "are patents related to two other lawsuits of Affymetrix Inc." This is consistent with (but does not add to) the Hyseq–Affymetrix litigation above; the '637 patent was the Oxford Gene Technology (Southern) patent, which was the subject of separate Affymetrix/OGT disputes and an EPO opposition in which Hyseq participated.
  5. Search limitations. I did not find evidence of any post‑2001 litigation (e.g., by successor entities Nuvelo/Callida Genomics) asserting the '940 patent, nor any other defendant apart from Affymetrix. My searches were limited in number, so this should be read as "none found," not a definitive negative.

Bottom line

The only known litigation involving U.S. 5,695,940 is the Hyseq, Inc. v. Affymetrix, Inc. dispute (with Affymetrix's mirror-image counterclaim actions) in the Northern District of California — consolidated in substance across C 97‑20188 RMW, C 99‑21163 JF, and C 00‑20050 RMW — which was settled and dismissed with prejudice in October 2001, with both parties acknowledging the validity and enforceability of the '940 patent.

Generated 9/30/2026, 3:11:08 PM

Proceedings on file (0)

All PTAB activity →

AIA trial proceedings (IPR / PGR / CBM) filed at the USPTO Patent Trial and Appeal Board against this patent. Sourced from the USPTO Open Data Portal and refreshed every six hours; each proceeding number deep-links to the PTAB E2E docket.

Current assignee: Hyseq, Inc.

No PTAB proceedings on file. This patent has not been challenged via IPR, PGR, or CBM. The absence is itself a signal — well-asserted patents eventually attract IPRs. The LLM analysis below may surface filings the ODP feed hasn’t indexed yet.

PTAB challenges

AIA trial proceedings at the USPTO Patent Trial and Appeal Board — IPR, PGR, and CBM. Petitioners, judge panels, claim-level invalidation outcomes from Final Written Decisions, and Federal Circuit appeals. The single most important defensive datapoint after litigation history.

✓ Generated

I'll start by verifying the PTAB record via web search, since the structured block indicates no AIA proceedings are indexed.

Let me run additional targeted searches to rule out any AIA proceedings and check for related USPTO activity.

Let me check for any reexamination history and confirm the PTAB record via the USPTO decisions portal.

Proceedings overview

Total AIA trial proceedings on file for US 5,695,940: 0. The USPTO Open Data Portal structured block returns no inter partes reviews, no post-grant reviews, and no covered business method reviews — so the breakdown by status is 0 active / 0 claims invalidated / 0 claims sustained / 0 settled / 0 institution denials. Bottom line for a defendant: there is no PTAB-based defense to inherit and no PTAB-based estoppel to worry about — but you almost certainly do not need one, because the patent expired on 2014-12-09 ("Anticipated expiration," "Expired - Fee Related") and any damages theory is time-barred by 35 U.S.C. § 286. The absence of IPR activity is best explained by the patent's age and expiration, not by its strength: the AIA trial window (petitions available from 2012-09-16) overlapped this patent's life for barely two years, and the patent's actual assertion history ran entirely through district court a decade earlier.

⚠️ Caveat on completeness: I could not query PTAB E2E / PTAB Decisions directly (the ptacts.uspto.gov search did not return a clean index result within my search budget). I relied on the ODP structured block as canonical plus web searches for "5,695,940" cross-referenced against IPR/PGR/CBM dockets. I found no proceeding number naming this patent. I cannot affirmatively prove a negative, but every hit for "5,695,940" in the PTAB document corpus was a prior-art citation inside someone else's proceeding (see pattern signals below), not a challenge to this patent.


No proceedings to report — the closest thing on record is district court litigation

Because there are zero AIA proceedings, the "most impactful proceeding" framing does not apply. For a defendant's benefit, here is what the public record actually shows, so you know what you are and are not dealing with.

Litigation flag (non-PTAB). Google Patents' family record carries a "First worldwide family litigation filed" entry sourced to Darts-IP (https://patents.darts-ip.com/?family=46248968). This is district court litigation data, not PTAB. It corresponds to Hyseq, Inc. v. Affymetrix, Inc., N.D. Cal., the two 1997 suits asserting US 5,202,231, US 5,525,464, and US 5,695,940 (https://www.biocentury.com/article/56155/markman-clarification-in-hyseq-affymetrix-suit).

  • Filed: second suit filed 1997-12-09, the same day the '940 patent granted.
  • Key procedural events: first Markman ruling 1999-10-26; revised Markman ruling announced 2000-08-02 by Judge Ronald M. Whyte, who clarified that determining from pre-existing sequence information that a fragment contains a known sequence, or determining differences from a known sequence, "is not sequencing as defined by the '231 patent" (https://www.siliconinvestor.com/readmsg.aspx?msgid=14148993).
  • Termination: settled October 2001 — a comprehensive cross-license under which Affymetrix took a minority stake and options in Callida Genomics and licensed the SBH technology, and Hyseq gained chip-fabrication rights; terms otherwise confidential (Hyseq 10-K, http://getfilings.com/o0000891618-02-001598.html; ATP/NIST case study, http://www.atp.nist.gov/eao/sp950-3/hyseq.pdf).
  • Appeal: no Federal Circuit appeal of a PTAB FWD exists, because no FWD exists.

Why there is no IPR. Three independent reasons, any one of which is dispositive:

  1. Expiration. Anticipated expiration 2014-12-09. The six-year § 286 lookback from the present date (2026-09-30) reaches back only to 2020-09-30 — entirely after expiration. There is no compensable infringement window left.
  2. Timing. AIA trials opened 2012-09-16; the patent had roughly a 27-month remaining life. A petitioner weighing the cost of an IPR against a patent about to expire has no rational economic incentive to file.
  3. Prior district court exposure already resolved the dispute. Affymetrix's invalidity counterclaim (filed 1997-12-11) was resolved by the 2001 settlement, not by any Patent Office validity proceeding.

Strategic summary

Claim status: untested before the PTAB, not canceled, but moot. No claim of US 5,695,940 has been canceled, confirmed, or even instituted upon in any AIA trial. There is therefore no claim-by-claim survival list to give you — the "CANCELED vs. SUSTAINED vs. UNTESTED" question resolves to: all claims are UNTESTED; none canceled; none sustained. I have no basis to state a claim count or to quote any FWD disposition for this patent, and I will not invent one. The patent's practical status comes from its expiration date, not from any adjudicated narrowing.

Estoppel landscape: no statutory estoppel exists. 35 U.S.C. § 315(e)(2) estoppel (and the CBM/PGR analogues) attach only to a petitioner that obtained a final written decision. With zero IPRs, there is no petitioner, no privity chain, and no estoppel — for anyone. Conversely, there is also no pool of "already-raised grounds" to inherit. Every prior-art ground is theoretically open in an Article III court, but that is a hollow benefit: the patent is expired, so there is no live infringement case in which to raise them. If you are receiving demand letters citing the '940 patent, the correct response is an expiration/§ 286 letter, not an IPR petition.

Pattern signals.

  • Same petitioner, multiple IPRs on this patent? No — no petitioner at all.
  • Patent owner PTAB appeal aggressiveness? None on this patent. The patent owner here (Hyseq → Nuvelo → Affymetrix security interest → Callida Genomics) litigated in district court and resolved by settlement, and never pursued an AIA trial. Note that the ownership trail matters: a 2004-12-14 security agreement lists Affymetrix and Nuvelo over Callida Genomics assets (per the Google Patents reassignment record).
  • Defensive aggregator (Unified Patents, RPX, etc.)? Unified Patents maintains a public profile page for US-5695940 (https://portal.unifiedpatents.com/patents/patent/US-5695940-A) — this is a catalog entry, not evidence of a Unified-filed challenge. No Unified IPR on this patent exists.
  • Watch for IPR noise. Searches for "Drmanac" and "5,695,940" return hits in other parties' proceedings where this patent or the Drmanac 1989 Genomics paper appears only as cited art — e.g. IPR2013-00308 (Ariosa, patent 8,296,076), IPR2017-02174, and the Complete Genomics v. Illumina district court record. Do not misread these as proceedings against the '940 patent.
  • The real risk is the family, not this patent. US 5,695,940 generated continuations that are still the relevant assertion targets in this lineage: US 5,972,619, US 6,316,191, US 2002/0106673, and US 7,230,093. If a demand letter reaches you, verify which patent in the family is actually being asserted before assuming it is the '940.

Recommended next steps

  1. If you are a defendant/recipient today: the patent expired 2014-12-09. Confirm the expiration via the USPTO Patent Center record for US 5,695,940 (https://patents.google.com/patent/[US5695940A](/patent/US5695940A)/en shows "Anticipated expiration 2014-12-09" and "Expired - Fee Related"). Any demand citing claims of the '940 patent is asserting a patent that cannot support a § 286 recovery window from a 2026 filing date. That is your dispositive answer — not a prior-art defense.
  2. If a demand letter cites a family member instead (e.g. 5,972,619; 6,316,191; 7,230,093), run a fresh PTAB check on that number specifically. The absence of IPRs on the '940 says nothing about its continuations.
  3. Do not file an IPR on the '940. No petitioner has ever done so, and with the patent expired there is no case or controversy rationale that justifies the cost; you would also be filing against a patent whose claims you would nonetheless need to show you have standing to challenge.
  4. If you want to confirm the null result independently (recommended given my search limitations), query PTAB E2E at https://ptacts.uspto.gov/ for patent number 5695940, and search the PTAB Decisions database at https://www.uspto.gov/PTAB for "5695940." The Darts-IP family link (https://patents.darts-ip.com/?family=46248968) will show the district court litigation but should not show AIA trials.
  5. Do not cite any FWD for this patent. There is none to link. Any brief or opinion-work-up that references a "PTAB decision on the '940 patent" would be a fabrication.

Bottom line: No PTAB activity on file — and the reason is structural, not defensive. US 5,695,940 has never been tested in an AIA trial, its claims have never been canceled, and it expired on 2014-12-09. A defendant facing an assertion built on this patent should lead with expiration and § 286; an IPR-based defense would be both unnecessary and unavailable as a practical matter. The genuine defensive work, if any, belongs to the surviving family members, not to the '940.

Generated 9/30/2026, 3:11:12 PM

Ownership chain (4)

Asserters network →

Structured records extracted from the assignment-history narrative below. Each entity links to its full ownership-network profile.

  1. ? · recorded 1996-10-21 · Change of Name

    SBHG CorporationHyseq, Inc.

    change of name only

  2. ? · recorded 1996-11-20 · Change of Name

    SBHG CorporationHyseq, Inc.

    change of name only

  3. 2004-09-21 · recorded 2004-09-22 · reel 15147/0990 · Assignment

    NUVELO, INC.Callida Genomics, Inc.

    Correspondent: Donna Rose-Burns

    internal reorg

  4. ? · recorded 2004-12-14 · Security Agreement

    Callida Genomics, Inc.AFFYMETRIX, INC. and NUVELO, INC.

    securitization

Assignment history

Inventors, original assignee, and the chain of ownership recorded with the USPTO — including the correspondent attorney who recorded each assignment, since shell-LLC chains often share one repeat-player attorney even when the entity names look unrelated. Surfaces NPE / patent-troll patterns: shell-entity transfers, known asserters in the chain, repeat correspondent fingerprints, pre-litigation assignments, and bankruptcy fire-sales.

✓ Generated

I'll reconstruct the assignment record using the sources available. Let me search for the recorded assignments.

Let me dig into the specific assignment records and the litigation history.

Assignment & Ownership Reconstruction — US 5,695,940

Verification caveat up front. The USPTO Assignment Center / Assignments-on-the-Web record for this patent could not be fully retrieved through the tools available to me in this session (the search budget was exhausted before I could pull the reel/frame index directly). Google Patents' "Legal Events" pane, which mirrors the Assignment Center data, does not display reel/frame numbers. I therefore have one verified reel/frame from a secondary index (plAInSite's mirrored USPTO assignment record) and the remainder as recorded conveyance types/dates. I have marked each entry's verification status accordingly and have not invented reel/frame values. Two records (2004-09-21 and 2004-12-14) I could corroborate against Nuvelo/ARCA SEC 10-K filings.

Sources used: Google Patents legal events for US5695940A, USPTO Assignment Center / Assignments on the Web, the mirrored USPTO record at plAInSite assignment 15147/990, Nuvelo/ARCA Biopharma 10-K filings (2004–2006), and Nature Biotechnology 15:406 (1997).


Inventors

Inventor Affiliation at priority filing (1987-04-01) Later affiliation
Radoje T. Drmanac Yugoslavia — the 1987 priority filing (YU P‑570/87) is described in Nature Biotechnology as filed by "a group from what was then Yugoslavia." The specific institution is not named in any source I retrieved; the commonly cited employer (Institute of Molecular Genetics and Genetic Engineering, Belgrade) is not verified here, so I flag it as unconfirmed. Argonne National Laboratory (Argonne, IL) as of 1997 per Nature Biotech.; later co-founder/officer of Callida Genomics, then SBH Genomics; subsequently associated with Complete Genomics and 10x Genomics–linked entities
Radomir B. Crkvenjakov Same as above (Yugoslavia; institution unconfirmed) Argonne National Laboratory as of 1997

Unusual pattern — flagged. The inventors did not assign to an institutional employer (e.g. Argonne); the assignee from the outset was the inventors' own vehicle, SBH Corporation (renamed Hyseq, Inc.). The more noteworthy pattern is at the other end of the chain: in December 2004 the SBH patents passed to SBH Genomics, Inc., a privately held Delaware corporation controlled by Radoje and Snezana Drmanac — i.e. the named inventor re-acquired his own patent family (see timeline, Dec 2004). That is a reacquisition-by-inventor pattern, not an inventor-departure/fire-sale pattern. Google Patents' "Current Assignee" field still reads Hyseq Inc, which is stale boilerplate and should not be treated as the present owner of record.


Original assignee

Hyseq, Inc. (Sunnyvale, CA), formerly SBHG Corporation — the "SBH" name derives from sequencing by hybridization, the claimed subject matter. Original assignee as printed on the face of the issued patent; the entity name change from SBHG Corporation to Hyseq, Inc. is itself recorded at the USPTO (see timeline).

  • Primary line of business: genomics / sequencing-by-hybridization technology — high-throughput gene discovery services, the "HyGenomics" database, and a DNA sequencing chip ("HyChip") per the CSHL HySeq corporate record. It is best characterized as an operating biotech tools-and-services company at the time it asserted this patent, not a licensing shell.
  • Product embodying the claims: partially. Hyseq commercialized SBH-derived tools/services, but the §101 subject matter of the '940 claims is a method (hybridize probes → detect → assemble sequence by maximal overlap), and Hyseq's revenue in the relevant years was dominated by screening-service collaborations (e.g. BASF, ~$21.9M in 2002) and licensing rather than by a mass-market product. I would call this an operating company with a services/chip offering, not a consumer product.
  • Current status: renamed/merged through a chain — Hyseq, Inc. → merged with Variagenics, Inc. (Jan 2003), combined entity renamed Nuvelo, Inc. → Nuvelo merged with ARCA Biopharma (2008). ARCA ticker ORKA subsequently rebranded (the same SEC filer is now surfaced as Oruka Therapeutics). The SBH patent assets themselves were divested before the Nuvelo/ARCA merger — they left Nuvelo in 2004 (below), so ARCA/Oruka does not appear to hold them.

Assignment timeline

Source note: entries marked (reel verified) carry a reel/frame I could read; entries marked (reel not retrieved) are corroborated by Google Patents legal events and/or SEC filings but I could not read the reel/frame index in this session. Correspondent fields could only be captured for entry #3.

  • 1996-10-21 (recorded) — Reel not retrieved

    • Conveyance: Change of Name
    • Assignor: SBHG CORPORATION
    • Assignee: HYSEQ, INC.
    • Correspondent: not captured in this session
    • Context: Change of name only — "SBH Corporation" (the inventors' original sequencing-by-hybridization vehicle) renamed Hyseq, Inc. No change in beneficial ownership.
  • 1996-11-20 (recorded) — Reel not retrieved

    • Conveyance: Change of Name
    • Assignor: SBHG CORPORATION
    • Assignee: HYSEQ, INC.
    • Correspondent: not captured in this session
    • Context: Second change-of-name recording of the same SBHG Corporation → Hyseq, Inc. event (Google Patents lists two 1996 change-of-name events, consistent with the same corporate renaming being recorded against multiple application/patent groupings). Change of name only.
  • 2004-09-21 (executed) / 2004-09-22 (recorded) — Reel 15147/0990 (reel verified)

    • Conveyance: Assignment (USPTO form wording: "Assignment Of Assignors Interest")
    • Assignor: NUVELO, INC.
    • Assignee: CALLIDA GENOMICS, INC., 670 Almanor Avenue, Sunnyvale, CA 94085
    • Correspondent: DONNA ROSE-BURNS, NUVELO, INC., 675 Almanor Avenue — in-house counsel/paralegal at the assignor, not an outside NPE-oriented firm. Single appearance in the chain; no recurrence, so no repeat-player signal.
    • Context: Internal reorganization — Nuvelo moved the SBH patent assets into its ~90%-owned subsidiary Callida Genomics in preparation for divesting Callida. (Callida had been set up in 2001 as the Hyseq/Affymetrix SBH joint vehicle following the October 2001 Affymetrix settlement.)
  • 2004-12-14 (recorded) — Reel not retrieved

    • Conveyance: Security Agreement
    • Assignor: CALLIDA GENOMICS, INC.
    • Assignee: AFFYMETRIX, INC. and NUVELO, INC. (as secured parties)
    • Correspondent: not captured in this session
    • Context: Securitization — the Callida patent portfolio (including the SBH family) was pledged as collateral for the convertible promissory notes issued in connection with the December 3, 2004 sale of Callida. Per Nuvelo's 10-K, "[t]he patents and patent applications owned by Callida are collateral for the notes."
  • 2004-12-03 (transaction closing; stock sale, not a patent-record assignment) — no separate reel identified

    • Conveyance: Sale of subsidiary stock (asset indirectly transferred)
    • Assignor: Nuvelo, Inc. (≈90% of Callida) and Affymetrix, Inc. (minority stake)
    • Assignee: SBH GENOMICS, INC., a privately held Delaware corporation controlled by Radoje and Snezana Drmanac, who were Callida employees/officers before the sale
    • Correspondent: n/a — stock purchase, disclosed in SEC filings rather than recorded as a patent assignment
    • Context: Divestiture/monetization — Nuvelo's sale of a non-core subsidiary; the named inventor re-acquired the portfolio. Earn-out of 2.5% of net annual revenues above $5M from sale/license of "certain Callida patents" for 10 years.
  • 2014-12-09 — not an assignment; anticipated term expiration recorded by Google Patents. The '940 patent expired 2014-12-09, consistent with the pre-URAA rule (17 years from the 1997-12-09 grant) because the application is a continuation of a chain rooted in a pre-June-8-1995 filing (Ser. No. 08/203,502, filed 1994-02-28).

Lead I could not verify and am flagging rather than asserting: the Unified Patents portal page for US-5695940-A surfaces 10x Genomics Inc and Affymetrix Inc alongside this patent. In context this appears to be related-portfolio/assertion-context metadata (Drmanac-linked later patents and the Affymetrix security interest), not a recorded assignment of the '940 patent to 10x Genomics. I found no reel/frame evidence of any post-2004 assignment. Treat any claim that 10x Genomics owns the '940 patent as unverified.


Timeline diagram

timeline
    title Ownership of US 5695940
    1987 : Priority filing in Yugoslavia
    1988 : First US application filed
    1996 : SBHG Corporation renamed Hyseq Inc
    1997 : Patent issues 9 December
         : Hyseq sues Affymetrix same day
    2004 : Nuvelo assigns patents to Callida Genomics
         : Security deal to Affymetrix and Nuvelo
         : Callida sold to SBH Genomics
    2014 : Patent term expires 9 December

NPE / troll-pattern signals

  1. Shell-entity transfer — unclear / weak-positive.
    The patents did move from an operating company (Nuvelo) into Callida Genomics, Inc. (reel 15147/0990, executed 2004-09-21), and then the Callida stock was sold to SBH Genomics, Inc., a privately held Delaware corporation whose revenue model under the deal was expressly licensing/sale of the patents (2.5% earn-out on net revenues from "sale of, or license under, certain Callida patents"). That is a licensing-oriented holding vehicle. However: (a) Callida's recorded address, 670 Almanor Avenue, Sunnyvale, is Nuvelo's own campus address — not a registered-agent service; (b) SBH Genomics is controlled by the named inventor and his spouse, i.e. a technology-continuation vehicle, not an anonymous third-party shell; (c) I found no registered-agent/CT Corporation-style address or single-purpose formation evidence. So the "no products / agent address / anonymous LLC" tells are not established. Marked unclear.

  2. Known asserter in the chain — not present.
    Assignees of record are SBHG Corporation/Hyseq, Nuvelo, Callida Genomics, Affymetrix and SBH Genomics. None of these appears on the reference NPE list (Acacia, Marathon, IV, IPNav, Wi-LAN, Mosaid/Conversant, Vringo, Pendrell, Innovatio, MPHJ, Lumen View, Round Rock, Document Generation, Spangenberg entities). Hyseq is an acquirer/asserter operating company, the opposite posture.

  3. Repeat correspondent across the chain — not present (data-limited).
    Only one correspondent was captured: Donna Rose-Burns, Nuvelo, Inc., 675 Almanor Avenue on reel 15147/0990. She appears once in this chain, is in-house at the assignor, and is not a known NPE recording attorney. The 1996 change-of-name records and the 2004-12-14 security agreement correspondents were not retrievable, so a repeat-player cannot be excluded with total confidence — but nothing in the captured data supports it. A single appearance is not a finding.

  4. Cascading transfers — present (mild).
    Two recorded events eight days apart in December 2004 (the 2004-12-14 security agreement) plus the 2004-09-21 assignment, plus the 2004-12-03 stock sale — effectively three ownership-affecting steps in ~90 days: Nuvelo → Callida → (security interest to Affymetrix/Nuvelo) → Callida stock to SBH Genomics. Chained-LLC-in-under-24-months yes; but the assignees do not share an agent address and do not share principals other than the Drmanac control of the terminal entity. Weak form of the signal.

  5. Pre-litigation transfer — not present.
    The first infringement suit naming the '940 patent (Hyseq v. Affymetrix, N.D. Cal.) was filed 1997-12-09, the same day the patent issued — filed by the original assignee against a competitor, roughly seven years before the first recorded post-issuance transfer (2004-09-21). No transfer was arranged to enable assertion; the assertion created the need for the later restructuring, not vice versa.

  6. Bankruptcy fire-sale — not present.
    No Chapter 7/11 proceeding. Nuvelo's 2004 Callida disposition was a voluntary divestiture of a non-core subsidiary; Nuvelo later merged with ARCA Biopharma (2008). No court-supervised patent sale.

  7. Privateering — not present.
    The opposite of the classic pattern: here the operating company (Hyseq) asserted against a competitor (Affymetrix) directly, and the ultimate transaction saw the portfolio pass toward the inventor rather than to an outside litigation proxy. No SEC/Patent Progress/EFF evidence of an operating company funding an NPE proxy against rivals.

  8. Defensive aggregator (anti-NPE) — not present.
    The chain does not terminate at RPX, AST, LOT Network, Unified Patents or OIN. It terminates at SBH Genomics, Inc. and the patent expired 2014-12-09 — neutralization here came from term expiry, not aggregation.


Verdict

Operating-company assertion.

Justification: the only owner that ever asserted this patent is the original assignee Hyseq, Inc., an operating SBH/genomics company that sued competitor Affymetrix in N.D. Cal. beginning 1997-12-09 — the day the patent issued — alongside the sibling SBH patents (US 5,202,231; 5,525,464). The subsequent record chain is a voluntary corporate reorganization and divestiture (Nuvelo → Callida Genomics, reel 15147/0990, executed 2004-09-21; security agreement to Affymetrix/Nuvelo recorded 2004-12-14; Callida stock sold to SBH Genomics on 2004-12-03), ending with the inventor-controlled SBH Genomics rather than with any listed NPE, and the patent expired 2014-12-09. No NPE-list entity, no repeat-player correspondent, no pre-litigation transfer and no bankruptcy sale appear in the record, so the NPE signals do not clear the "2+ strong" or even "1 strong" threshold. Confidence is limited by the fact that I could not read the reel/frame index for four of the entries and cannot rule out a later, unrecorded or overseas assignment — verify at the USPTO Assignment Center (and the mirror at assignment.uspto.gov) by searching patent number 5695940, and cross-check the Nuvelo/ARCA 10-K disclosures for the December 2004 Callida/SBH Genomics transaction.

Generated 9/30/2026, 3:11:39 PM

Prior art

Earlier patents, publications, and products that may anticipate or render the claims unpatentable.

✓ Generated

I'll research US 5695940 and its cited prior art systematically.

I have initial data. Now let me get the exact "References Cited" section on the face of US 5,695,940 and its claims.

I have the claims. Now let me pull the exact "References Cited" list on the face of US 5,695,940.

Prior‑Art Analysis — US 5,695,940

Scope and sourcing note

The authoritative full text supplied for US 5,695,940 is truncated (it ends mid‑§5.2 and does not include the "References Cited" front page or the claims). I therefore built this analysis from:

I was not able to open the USPTO Patent Center / Patent Public Search record directly in this session, so the citation list below is the printed‑patent list as mirrored, not a live USPTO API pull. Where I could not confirm an inventor, title, or filing date with high confidence, I say so rather than guess.

⚠️ Identifier caution: search results also surface US 5,695,840 (Walter B. Mueller, "…") and US 5,695,940. These are different documents. Everything below refers only to 5,695,940.


1. Patent identity (as printed)

Field Value
Patent number US 5,695,940 A
Title Method of sequencing by hybridization of oligonucleotide probes
Inventors Radoje T. Drmanac; Radomir B. Crkvenjakov (Belgrade, YU)
Assignee (as listed) Hyseq, Inc. (Sunnyvale, CA)
Appl. No. 08/460,853
Filed June 5, 1995
Granted December 9, 1997
Priority April 1, 1987 (Yugoslavian Application P‑570/87); also YU 18617‑P 570/87, Sept. 18, 1987
Continuity Continuation of 08/203,502 (filed Feb. 28, 1994, now US 5,525,464) → file‑wrapper continuation of 08/048,152 (Apr. 15, 1993, abandoned) → continuation of 07/576,559 (Aug. 31, 1990, abandoned) → CIP of 07/175,088 (Mar. 30, 1988, abandoned)
Class C12Q 1/68; US Cl. 435/6, 536/23.1, 536/24.33
Status Expired – Fee Related (anticipated expiration 2014‑12‑09)

Not a legal conclusion, but the stated effective priority is 1987‑04‑01, with the earliest U.S. filing 1988‑03‑30.


2. The claims at issue

US 5,695,940 has only three claims (reproduced from the printed patent at everypatent.com):

Claim 1 — Method of sequencing a target nucleic acid of unknown sequence:
(a) using conditions which differentiate an exactly complementary probe from a single‑mismatch probe;
(b) contacting a plurality of oligonucleotides, each six to ten nucleotides in length, with the target;
(c) forming a duplex; (d) washing the duplex; (e) detecting positively hybridizing oligonucleotides; and
(f) compiling a sequence of the target from overlapping positively‑hybridizing oligonucleotides.

Claim 2 — Partial sequencing: same (a)–(f), but a plurality (less than the totality) of probes each at least six nucleotides in length, compiling a partial sequence from overlapping hybridizing probes.

Claim 3 — Claim 2 wherein the probes are six to ten nucleotides in length.

Because the patent's distinguishing feature is (i) short (6–10 nt) probes and (ii) sequence assembly by overlap, the §102 analysis turns almost entirely on whether a cited reference discloses sequencing by hybridisation of short probes with overlap assembly — with the relevance date being the crux, since most cited documents either post‑date 1987‑04‑01 or disclose only a sub‑element.


3. U.S. patent documents cited on the face of US 5,695,940

As printed (number | date | inventor | class):

# Patent Date Inventor Class
1 4,562,159 Dec. 1985 Shafritz 435/5
2 4,591,567 May 1986 Britten et al. 435/285
3 4,613,566 Sep. 1986 Potter 435/6
4 4,672,040 Jun. 1987 Josephson 436/526
5 4,675,283 Jun. 1987 Roninson 435/6
6 4,683,195 Jul. 1987 Mullis et al. —
7 4,683,202 Jul. 1987 Mullis 435/91
8 4,720,786 Jan. 1988 Hara 364/413
9 4,766,062 Aug. 1988 Diamond et al. —
10 4,770,992 Sep. 1988 Van den Engh et al. —
11 4,794,073 Dec. 1988 Dattagupta et al. —
12 4,849,334 Jul. 1989 Lorincz 435/5
13 4,865,967 Sep. 1989 Shiraishi et al. —
14 4,865,968 Sep. 1989 Orgel et al. 204/462
15 4,942,124 Jul. 1990 Church 435/6
16 5,002,867 Mar. 1991 Macevicz 435/6
17 5,149,625 Sep. 1992 Church et al. —
18 5,202,231 Apr. 1993 Drmanac et al. —
19 5,492,806 Feb. 1996 Drmanac et al. —
20 5,525,464 Jun. 1996 Drmanac et al. —

4. Reference‑by‑reference §102 relevance

Tier A — Potentially anticipatory (or disclosure‑level relevant)

US 5,002,867 — Macevicz, "Nucleic Acid Sequence Determination by Multiple Mixed Oligonucleotide Probes" (granted Mar. 1991; earliest priority date reported as 1988‑04‑24).
This is the single most on‑point patent citation in the list: it concerns determining nucleic‑acid sequence using sets of oligonucleotide probes rather than gel electrophoresis. It is the closest thing in the cited patent art to SBH.

  • §102 exposure: Potential §§102(a)/(b) disclosure as to the general "determine sequence with probes" concept → claims 1, 2 (and 3 by dependency).
  • But the date defeats it as §102(a)/(b) art against this patent's claims if those claims are entitled to the 1987‑04‑01 / 1988‑03‑30 dates: Macevicz's earliest priority (1988‑04‑24) is after the Yugoslav priority and after the 1988‑03‑30 U.S. filing. It could only operate as §102(e)/§102(a)(2) art (its U.S. filing date) against claims that are not entitled to those earlier dates — which is precisely the vulnerability the Examiner would have probed. I cannot resolve the priority entitlement question from the truncated record.

US 4,865,968 — Orgel et al. (Salk Institute), "DNA Sequencing" (granted Sep. 1989; priority date reported as 1985‑03‑31).
Orgel‑type "DNA sequencing" subject matter is cited among the sequencing‑by‑hybridisation‑adjacent art. It predates the 1987 priority, so it is available as §102(a)/(b) art if it discloses probe hybridisation + ordered assembly.

  • §102 exposure: potentially claim 1 (and 2/3) — only if it discloses overlap assembly of hybridised probes. I cannot confirm from the available text that it discloses short‑probe (6–10 nt) discrimination plus overlap compilation, so I flag this as unverified.

Tier B — Cited for sub‑elements; not anticipatory of the claims

These disclose isolated claim elements (labels, supports, washing, detection, PCR, gel‑image handling) but no overlap‑assembly sequencing step, so they cannot anticipate claims 1–3 individually:

Patent Reported inventor/assignee & subject Element it maps to §102
4,613,566 Potter; "Hybridization Assay and Kit Therefor" (assignee reported as Harvard; priority 1984‑01‑22) hybridisation assay format Not anticipatory
4,562,159 Shafritz hybridisation detection/support Not anticipatory
4,591,567 Britten et al. nucleic‑acid binding to support Not anticipatory
4,672,040 Josephson; "Magnetic Particles for Use in Separations" solid‑phase separation ("washing"/handling) Not anticipatory
4,675,283 Roninson DNA handling/detection Not anticipatory
4,683,195 / 4,683,202 Mullis et al. / Mullis — PCR target amplification preparatory to hybridisation Not anticipatory
4,720,786 Hara — "Method of Compensating for Offset Distortion in Rows of Electrophoretic Patterns" (priority 1985‑04‑18) automated gel‑image reading (background) Not anticipatory
4,766,062 Diamond et al. detection/labelling Not anticipatory
4,770,992 Van den Engh et al. — "Detection of Specific DNA Sequences by Flow Cytometry" detection modality Not anticipatory
4,794,073 Dattagupta et al. (assignee reported Bayer AG) — "Detection of Nucleic Acid Hybrids by Prolonged Chemiluminescence" detection step (e) / labels Not anticipatory
4,849,334 Lorincz — HPV‑43 hybridisation probes (assignee reported Digene/Qiagen) probe hybridisation to targets Not anticipatory
4,865,967 Shiraishi et al. (assignee reported Fujifilm) — "Autoradiographic Gene‑screening Method" array/dot hybridisation screening & autoradiography → relates to steps (b)/(e) Not anticipatory
4,942,124 Church — "Multiplex Sequencing" (priority 1987‑08‑10) multiplex sequencing (gel‑based, not SBH) Not anticipatory; post‑dates the 1987 priority in any event
5,149,625 Church et al. — "Multiplex Analysis of DNA" multiplex DNA analysis Not anticipatory

Tier C — Applicant's own family / related disclosures (cannot be §102 prior art)

US 5,202,231; US 5,492,806; US 5,525,464 — all "Drmanac et al."

  • US 5,525,464 is the immediate parent (Ser. No. 08/203,502) named in this patent's own continuity statement.
  • US 5,202,231 ("Method of sequencing of genomes by hybridization of oligonucleotide probes") and US 5,492,806 ("Method of determining an ordered sequence of subfragments of a nucleic acid fragment by hybridization of oligonucleotide probes") are the applicants' own earlier/related Hyseq filings.
  • §102: these are same‑inventor / commonly‑owned family members, not "by others." They are cited for continuity/awareness, not as §102 art. They cannot anticipate claims 1–3.

5. Foreign patent documents cited

Reported alongside US 5,695,940's citation set (metadata from Unified Patents mirror; earliest‑priority dates as reported — treat with care):

Document Reported priority Reported owner / subject §102 relevance
EP 0 197 266 A2 1985‑02‑25 Sagax Instrument AB — "Method and Support for Analysing Sequences of Nucleic Acids" Probe/array hybridisation analysis; closest foreign art to claims 1–2 on the "support + probe hybridisation" concept; not shown to disclose overlap assembly → likely not anticipatory
WO 88/01302 A1 1986‑08‑10 Siska Diagnostics Inc. — "Nucleic Acid Probe Assay Methods and Compositions" Hybridisation assay; sub‑element only
WO 89/10977 A1 1988‑05‑02 Oxford University Innovation (Southern) — "Analysing Polynucleotide Sequences" Oligonucleotide arrays for sequence analysis — highly relevant subject matter, but its earliest priority (1988‑05‑02) post‑dates the 1987‑04‑01 / 1988‑03‑30 dates, so only a late‑priority‑date scenario gives it §102(a)(2)/102(e) force
WO 90/03382 A1 1988‑09‑20 "Support‑bound Oligonucleotides" Support‑bound probe arrays; post‑dates the 1987 priority
EP 0 152 886 A not confirmed (title not confirmed in retrieved sources) Cannot assess; flagged unverified

6. Most relevant non‑patent literature cited (for completeness)

The front page cites 111 non‑patent references. The ones that bear directly on claims 1–3 are:

  • Wallace et al., Nucleic Acids Res. 6:3543 (1979) — discriminates perfect vs. single internal mismatch with 11–17‑mers. Directly relevant to claim 1 step (a) and to the patent's stated novelty (shortening probes below 11 nt).
  • Wood et al., PNAS 82:1585 (1985) — 11–20‑mers in 3 M tetramethylammonium chloride.
  • Besmer et al., J. Mol. Biol. 72:503 (1972); Estivill et al., Nucleic Acids Res. 15:1415 (1987); Smith, in Methods of DNA and RNA Sequencing (1983) — short‑oligonucleotide hybridisation behaviour/statistics.
  • Breslauer et al., PNAS 83:3746 (1986); Craig et al., J. Mol. Biol. 62:383 (1971); Porschke & Eigen, J. Mol. Biol. 62:361 (1971); Ikuta et al., Nucleic Acids Res. 15:797 (1987) — duplex thermodynamics/melting kinetics (basis for steps (a) and (d)).
  • Maxam & Gilbert (1977); Sanger et al. (1977) — the conventional sequencing background being displaced.

None of these, on their face, discloses the complete claim‑1 combination (6–10 nt probes + discrimination conditions + washing + overlap compilation into a target sequence); they are cited as the state of the art in short‑oligo hybridisation thermodynamics and mismatch discrimination.


7. Bottom line

  1. Only one cited earlier patent is genuinely on‑point for the invention's core: US 5,002,867 (Macevicz). It is the reference most likely to have been the focus of a §§102/103 rejection against claims 1–3 — but its effective date falls after this patent's 1987‑04‑01 priority, so it can only bite as §102(e)/102(a)(2) art if the claims are pushed to a later effective filing date.
  2. US 4,865,968 (Orgel et al.) is the other pre‑1987‑priority patent in the list whose title ("DNA Sequencing") makes it potentially relevant; I could not verify from available sources that it discloses overlap assembly of short‑probe hybridisation data, so its §102(c)‑style anticipation of claim 1 is unconfirmed.
  3. The overwhelming majority of the cited patents (Tier B) disclose only sub‑elements — labelling/chemiluminescence detection (4,794,073), supports/magnetic separation (4,672,040, 4,591,567), dot‑blot screening and autoradiography (4,865,967), multiplex/gel sequencing (4,942,124, 5,149,625), and PCR (4,683,195 / 4,683,202). None anticipates claims 1, 2 or 3.
  4. US 5,202,231; US 5,492,806; US 5,525,464 are the applicants' own family members (US 5,525,464 is the named parent application) and are not available as §102 prior art.
  5. The foreign documents with the closest subject matter (WO 89/10977 – Southern; WO 90/03382; WO 88/01302; EP 0 197 266) all carry reported priority dates in the 1988–1989 window, i.e. at or after this patent's 1987 priority — so they function as background/late §102(a)(2)‑type art at best.
  6. The real §102 vulnerability of claims 1–3 is a priority‑date question, not a missing‑reference question: i.e. whether the 6–10 nt limitations of claims 1 and 3 are supported by the 1987 Yugoslav application / 1988‑03‑30 U.S. filing. That is exactly the line along which US 5,002,867 and WO 89/10977 would become §102 art. I cannot resolve it from the truncated record and flag it as the key open issue.

8. Express caveats

  • I did not retrieve the USPTO Patent Center / Patent Public Search record for 5,695,940 directly; the citation list above is the printed‑patent list as mirrored third‑party databases. A live USPTO pull should be used to confirm the list and to add any references added by amendment or examiner citation.
  • Titles, assignees and dates marked "reported" come from the Unified Patents mirror and were not independently verified at the USPTO; the printed "References Cited" as mirrored at everypatent gives number/date/inventor/class only.
  • §102 characterisations above are analytical flags, not legal conclusions, and are made without the benefit of the full prosecution history (e.g., any examiner‑cited art, 37 CFR 1.131/1.132 declarations, or priority‑benefit determinations) which would materially affect the analysis.
  • I did not auto‑correct any identifier; all numbers are reproduced as they appear in the sources, including the "4766062 / 4720786 / 4794073" formatting of the printed list.

Generated 9/30/2026, 3:11:44 PM

Obviousness

Combinations of prior art that suggest the claimed invention would have been obvious under 35 U.S.C. § 103.

✓ Generated

I'll research the prior art cited on this patent's page before analyzing obviousness.

Let me dig deeper into the specific cited prior art references and the Similar/Prior Art listings.

Obviousness Analysis — U.S. Patent 5,695,940 (Drmanac & Crkvenjakov)

Source patent: https://patents.google.com/patent/[US5695940A](/patent/US5695940A)/en
Prior-art inventory used: the "Prior Art" / cited-reference listings on the Google Patents page and the mirrored Unified Patents record at https://portal.unifiedpatents.com/patents/patent/US-5695940-A

Caveat up front: The fetched patent text I was given does not include the verbatim "Patent Citations (26/31)" and "Non-Patent Literature (111)" tables — those were stripped in the retrieval. My inventory below is reconstructed from the Google Patents "Prior Art"/citations listing and the Unified Patents portal rendering of the same page, and from the references the specification itself cites. Where I cannot verify a reference's actual disclosure, I say so rather than assume it.


1. The claims at issue

Claim 1 (method of sequencing a target nucleic acid of unknown sequence) requires:

  • (a) conditions that differentiate an exactly complementary probe from a probe having a single mismatched nucleotide;
  • (b) contacting a plurality of oligonucleotides, each from six to ten nucleotides in length, with the target;
  • (c) forming a duplex; (d) washing the duplex; (e) detecting positively hybridizing oligonucleotides; and
  • (f) compiling the target sequence from overlapping positively-hybridizing oligonucleotides.

Claim 2 is the "partial sequencing" variant — a plurality but less than a totality of probes, each at least six nucleotides.
Claim 3 narrows claim 2 to six to ten nucleotides.

Two limitations carry the entire §103 debate: (i) the ≤10-nt probe length, and (ii) the step (f) assembly-by-overlap information step.


2. Threshold issue: the effective filing date controls which references even qualify

The priority chain recited on the face of the patent is:

YU P-570/87 (1987-04-01) → YU 18617-P 570/87 (1987-09-18) → US 07/175,088 (filed 1988-03-30, abandoned) → US 07/576,559 (filed 1990-08-31, abandoned, a CIP) → US 08/048,152 (1993-04-15) → US 08/203,502 (1994-02-28, now US 5,525,464) → US 08/460,853 (1995-06-05) → US 5,695,940.

This matters enormously:

  • If claims 1–3 get the 1987-04-01 (or 1988-03-30) date, then several of the 26 listed patent references are not prior art at all: US 5,002,867 (Macevicz, priority 1988-04-24), WO 89/010977 (Isis/Oxford/Oxford University Innovation, priority 1988-05-02), WO 90/03382 (priority 1988-09-20), WO 90/04652 (DNAX, priority 1988-10-23), and Drmanac's own 1989/1990 papers all post-date it.
  • If the six-to-ten-nucleotide limitations are only supported by the 1990 CIP (07/576,559, filed 1990-08-31) — which is plausible, since the SOH "short oligonucleotide hybridization" data (6-, 7-, 8-mers) is the CIP's contribution — then the critical date shifts to 1990-08-31, and all of the above become available. That converts a moderately defensible patent into a highly vulnerable one.

Any serious §103 challenge must first litigate this date. I flag it because the answer changes materially in each case.

Also note: US 5,202,231, US 5,492,806, and US 5,525,464 appear in the citation list but are the same family / same inventive entity (Drmanac, priority 1987-04-01). They are not §102/§103 prior art against this patent.


3. The genuinely pre-1987/88 prior art (the strong set)

Reference Date Teaching (as relevant)
Wallace et al., Nucl. Acids Res. 6:3543 (1979) — cited in spec §2.1, 2.2 1979 Conditions that differentiate a perfect 11–17-mer hybrid from one with a single internal mismatch; discrimination driven by hybridization stringency + washing.
Wood et al., Proc. Natl. Acad. Sci. 82:1585 (1985) 1985 3 M tetramethylammonium chloride makes Tm depend on probe length only, independent of GC content — i.e., a route to a single uniform set of hybridization conditions.
Maxam–Gilbert, PNAS 74:560 (1977); Sanger et al., PNAS 74:5463 (1977) 1977 Gel-based sequencing; establishes the problem (slow, manual, not automatable/scalable).
Smith, in Methods of DNA and RNA Sequencing (1983) 1983 Predicts the probe length needed for a probe to be unique in the human genome (16–17mers) and, conversely, the exponential increase in occurrence frequency as probes shorten.
Besmer et al., J. Mol. Biol. 72:503 (1972); Estivill et al., Nucl. Acids Res. 15:1415 (1987) 1972 / 1987 Prior work with short oligomers; per the specification, no reproducible, uniform set of conditions for <11-mers.
Ikuta et al., Nucl. Acids Res. 15:797 (1987); Thein & Wallace, Human Genetic Diseases: A Practical Approach (1986) 1987 / 1986 Washing as the mechanism to distinguish matched from mismatched hybrids; the "single mismatched nucleotide" discrimination element (claim 1(a), (d)).
EP 0197266 A2 (Sagax Instrument AB; Nygren & Stenberg; priority DE 3506703, 1985-02-26) 1985 Immobilizing a defined-sequence nucleic acid strand on a solid support and hybridizing denatured target to it, detecting the hybridization (there, ellipsometrically). This is the support-bound-probe/array format.
US 4,591,567 (Caltech, 1982-04-20) 1982 "Recombinant DNA Screening System Including Fixed Array Replicator and Support" — arraying clones/fragments on a support and screening them by hybridization. Supplies the "array of target fragments" half of claim 1(b).
US 4,766,062 (Honeywell) 1984 Displacement polynucleotide assay — homogeneous hybridization format.
US 4,613,566 (Harvard, 1984) 1984 Hybridization assay and kit.
US 4,865,967 (Fuji, 1983-06-28) 1983 "Autoradiographic gene-screening method" — the signal readout for claim 1(e).
US 4,865,968 (Salk Institute, filed 1985-03-31) 1985 Titled "DNA sequencing" and cited in the patent-art list. I have not verified its specific disclosure; I therefore do not rely on it, but it is worth checking for gel-free sequencing teachings.
US 4,683,195 / US 4,683,202 (PCR, 1985–86) 1985–86 Amplification to generate sufficient target material.
Poustka et al., Cold Spring Harb. Symp. Quant. Biol. 51:351 (1986); Craig et al. (1986); Michiels et al., CABIOS 3:203 (1987) — cited in spec §2.4 1986–87 Hybridizing collections of ~100 specific oligonucleotides to arrays of 3–10 × 10⁶ colony filters and using the patterns to map/fingerprint clones. The specification itself concedes these give localization but "does not provide desired and useful sequence information."
Saiki et al., Science 239:487 (1986) (as cited in the patent) 1986 Amplification of 1000-bp stretches from two flanking primers + dot-blot detection of mutants with oligonucleotide probes.
US 4,942,124 / US 5,149,625 (Church) 1987–88 Multiplex sequencing / multiplex DNA analysis — barcoding and parallel processing of many fragments.

Post-1987 but potentially available on the CIP theory:

  • US 5,002,867 (Macevicz) — "Nucleic Acid Sequence Determination by Multiple Mixed Oligonucleotide Probes" (priority 1988-04-24), and its PCT twin WO 90/04652 (DNAX, priority 1988-10-23). By title and field, this is the closest single reference — it purports to determine sequence from the binding pattern of families of mixed probes. I have not read its claims/specification, so I cannot state how it handles probe length or connection/assembly; that must be verified before relying on it.
  • WO 89/010977 (Isis Innovation / Oxford University Innovation; Southern) — "Analysing Polynucleotide Sequences" — the array-based sequencing concept.
  • WO 90/03382 — "Support-bound oligonucleotides."
  • Drmanac et al., Genomics 4:114–128 (1989) and Drmanac et al., DNA & Cell Biology 9(7):527–534 (1990) — the inventor's own theory papers (not prior art against him, but evidence of what the field considered the state of the art).

4. The Graham/KSR framework applied

Level of ordinary skill: a molecular biologist with several years of hybridization experience (the specification's own experimenters), plus access to competent software engineers (the specification's algorithm was written in Microsoft QuickBASIC 2.0 on a 6–10 MHz IBM PC/AT — i.e., utterly routine programming).

The problem the field was trying to solve is set out by the patent itself: the Human Genome Project push (Lewin, Science 232:1598 (1986); Wada, Nature 325:771 (1987); Smith & Hood, Bio/Technology 5:933 (1987)), the ≈100 bp/person/day gel throughput ceiling, and the projected $3B/10-year cost. That is exactly the kind of "design incentive … market force" and "recognized problem in the field" that KSR holds supplies the motivation to combine.


5. The combinations

Combination A — Wallace '79 + Wood '85 + Sagax EP 0197266 + Caltech US 4,591,567 (+ Fuji US 4,865,967, +/- PCR)

This is the classic §103 mosaic and it maps claims 1(a)–(e) almost element-for-element:

  • (a), (d) — Wallace '79 + Ikuta '87 + Thein & Wallace '86 teach hybridization under conditions, followed by washing, that differentiate perfect hybrids from single-mismatch hybrids.
  • (b), (c) — Wood '85 supplies the motivation and the enabling technique for one uniform set of conditions across probes of different sequence (Tm determined by length, not GC), which is precisely the premise of claim 1(a). Sagax EP 0197266 teaches hybridizing target to immobilized, defined-sequence nucleic acid probes on a support; Caltech '59,1567 teaches the reciprocal array of cloned fragments on a support.
  • (e) — Fuji US 4,865,967 and the general autoradiographic screening art.
  • (f) — the weak link; see §6.

Motivation: every one of the four independent problems — (1) get more mismatch discrimination, (2) standardize conditions, (3) run many probes in parallel on a solid support, (4) generate enough target — is separately addressed by one of the references, and all four must be solved together to deliver a scalable, non-gel sequencing method that the field was openly demanding.

Combination B — Combination A + Poustka '86 / Craig '86 / Michiels '87 (pattern-based oligo hybridization to arrays)

Poustka/Craig/Michiels already teach hybridizing defined oligonucleotide sets to arrays of cloned DNA and reading out a binary pattern of positives. Adding them to Combination A supplies the "plurality of oligonucleotides … detect positively hybridizing" step in an array format verbatim. The only remaining gap is turning the pattern into letters rather than a clone fingerprint. The specification admits this gap in its own §2.4 ("Such identification however does not provide desired and useful sequence information").

Combination C — Macevicz US 5,002,867 (and/or WO 90/04652) + Wallace '79 / Ikuta '87

Available only if the claims are entitled to no earlier than the 1990 CIP date (1990-08-31). Macevicz is the most dangerous reference because it is directed at the same statutory purpose — nucleic acid sequence determination by multiple mixed oligonucleotide probes — and appears to teach determining sequence from which probes in a set hybridize. Combined with Wallace/Ikuta for the mismatch-discrimination and wash conditions, this renders claim 1's method obvious on paper. However, I must be candid: I have not verified Macevicz's disclosure, so I cannot assert that it renders the six-to-ten-nucleotide limitation or the overlap-assembly step obvious. That verification is the single highest-value next step in this analysis.

Combination D — for the assembly step (f) specifically

No pre-1987 reference that I can identify teaches "compiling a sequence from overlapping positively-hybridizing short oligonucleotides." The closest are (i) the general shotgun-assembly art of Sanger/Maxam-era sequencing (assembling sequence from overlapping fragments by computers), and (ii) the probe-length/uniqueness mathematics of Smith (1983). If one accepts that (f) is a routine data-processing step performed on a general-purpose computer, KSR's "predictable variations" and "known technique, known result" rationales make (f) the easiest element to attack — but it is the element with the least direct reference support on this record.


6. Motivation to combine — the affirmative case

  1. A finite, small set of known options. Once one wants non-gel sequencing, the art offered only the hybridization/array format (Sagax, Caltech, Poustka), and discrimination via stringency and washing (Wallace, Ikuta, Thein & Wallace). Combining them is not an unpredictable leap.
  2. Uniform conditions were an expressly recognized desideratum and Wood '85 provided a concrete way to achieve it.
  3. KSR "design incentive." The genome-project literature cited in the patent's own background created the motivation.
  4. Parallelism was standard practice. Poustka/Craig/Michiels were already running ~100 oligo probes against 3–10 × 10⁶ colony filters.
  5. Assembly by overlap was routine computing, done in QuickBASIC on commodity hardware per the specification.

7. The strongest nonobviousness counter-arguments (these are substantial)

  1. Teaching away. The specification's own §2.2 states: "as disclosed in these references eleven mer oligonucleotides are the shortest ones that generally can be hybridized successfully, reliably and reproducibly using known hybridization conditions," and that probes longer than 15 bases "discriminate end mismatch with difficulty" (Wood '85). Wallace '79 and Wood '85 thus bracket the claimed 6–10-mer range and point away from it. End-mismatch discrimination is affirmatively harder than internal-mismatch discrimination (spec §2.1). This is a strong argument that claims 1 and 3 were nonobvious as of 1987.
  2. Unexpected results / new property. The claimed invention's asserted discovery is that a single set of conditions can discriminate perfect matches from end mismatches down to six nucleotides, with D values of 2–40 for 102 of 105 probes (average ~10.6). That is a property the art did not possess and did not predict.
  3. Pioneering status / secondary considerations. The patent is foundational SBH art; note also the litigation flag on the family (first worldwide family litigation; the patent appears in the Complete Genomics v. Illumina, D. Del. 1:19-cv-00970 record), which is at least consistent with commercial significance.
  4. Weakness of (f). Combination A/B do not actually supply the sequence-reconstruction step; if the examiner/defender insists on a full element-by-element mapping, the mosaic fails on (f).

8. Bottom line

  • Under the 1987/1988 priority date: claims 1–3 are, in my assessment, likely nonobvious. Combinations A and B fail to reach step (f), and the Wallace '79 / Wood '85 bracket plus the specification's admission that <11-mers were not reliably usable amounts to a genuine teaching away from the six-to-ten-nucleotide limitation. A §103 rejection would need a reference squarely teaching sequence determination (not clone fingerprinting) from short-probe hybridization.
  • If the claims are limited to the 1990 CIP date: the analysis flips. US 5,002,867 (Macevicz) and WO 90/04652 (DNAX) become available, are directed to the very same purpose, and — combined with Wallace '79/Ikuta '87 for the discrimination-and-wash elements and the Sagax/Caltech/Poustka array art — would support a strong §103 rejection of at least claims 1 and 3, with claim 2 attacked as broader still (any length ≥6, mere "less than a totality").
  • Highest-value verification steps before finalizing: (i) confirm whether the 6–10-mer limitations are enabled/supported only by the 1990 CIP; (ii) obtain the full text and claims of US 5,002,867 and WO 90/04652; (iii) obtain US 4,865,968 (Salk) and WO 89/010977 (Isis/Oxford) to test whether they supply the assembly step; (iv) confirm the publication date of Estivill et al., Nucl. Acids Res. 15:1415 (1987) relative to 1987-04-01.

I've flagged above every point where I am inferring rather than relying on a verified disclosure — in particular, I have not verified the contents of US 5,002,867, WO 90/04652, US 4,865,968, or WO 89/010977, and those should be read directly before any rejection or validity opinion is finalized.

Generated 9/30/2026, 3:11:49 PM

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