Invalidity dossier
US 4921805
Nucleic acid capture method
Current assignee: Life Technologies Inc
Added 9/26/2026, 3:46:51 PM
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Patent summary
Title, assignee, inventors, filing/issue dates, abstract, and a plain-language overview of the claims.
I'll search for this specific patent number and check for any 2026 litigation activity.
US 4,921,805 — Summary
Searches performed: I queried for the literal number "4921805" (with title/assignee context) and separately for "US4921805 + litigation/CAFC 2026 docket." The patent record itself was retrieved. I found no CAFC 2026 docket activity, no district court litigation, and no PTAB proceeding tied to patent 4,921,805 in the results returned. I want to be explicit about uncertainty: absence from these search results is not proof of absence from PACER/PTAB/CAFC systems, but given the expiration status below, active 2026 litigation is highly improbable.
Bibliographic data (from Google Patents and FreePatentsOnline)
| Field | Value |
|---|---|
| Patent number | US 4,921,805 |
| Title | Nucleic acid capture method |
| Inventors | Gulilat Gebeyehu; Leonard Klevan; John D. Harding |
| Assignee (original & current) | Life Technologies, Inc. |
| Application no. | US 07/414,728 |
| Filing date | 1989-09-29 |
| Priority date | 1987-07-29 |
| Issue/grant date | 1990-05-01 |
| Status | Expired – Lifetime (anticipated expiration 2007-07-29) |
| Relationship | Continuation of Serial No. 07/078,991, filed 1987-07-29, now abandoned |
| Classifications | C12Q 1/68, 1/6806, 1/6813, 1/6834; Y10T 436/255 |
Source: https://patents.google.com/patent/US4921805/en and https://www.freepatentsonline.com/4921805.html
Abstract (as issued)
"A nucleic acid capture reagent which comprises one or more molecules that are capable of intercalation into nucleic acids and are attached to a solid support via a molecular linker. This capture reagent is useful for the separation and isolation of nucleic acids from complex unpurified biological solutions such as serum, sputum, blood, and urine. The resulting capture reagent-nucleic acid complexes are easily isolated from the sample solution by mechanical or magnetic means and the bound nucleic acids are released by simple chemical treatment."
Claim set
There is exactly one independent claim (claim 1); claims 2–10 are all dependent (10 claims total, per the patent's "Claims (10)" listing).
Claim 1 — the sole independent claim (plain language):
A method of separating nucleic acids from an unpurified biological sample, with three steps:
- (a) Contact the unpurified sample with a capture reagent made of three parts: (i) a solid support; (ii) a linker that is spermine or spermidine, bound to the support; and (iii) a methidium moiety bound to that linker — where the methidium must be able to bind the sample's nucleic acids "independent of the salt concentration of said sample" — thereby forming a sample–capture reagent mixture;
- (b) Incubate that mixture for a time and under conditions sufficient for the reagent to bind nucleic acids, forming a capture reagent–nucleic acid complex; and
- (c) Isolate the complex from the mixture.
⚠️ OCR note: the claim text as published renders step (b) as "insulating said sample-capture reagent mixture." This is an obvious typographical/OCR corruption of "incubating." I am flagging it rather than silently correcting it, per the strict-identifier rule, but the surrounding specification ("incubated for a time sufficient to allow binding") confirms the intended word.
Dependent claims 2–10 (plain language):
- 2 — The isolating step of claim 1 is done by centrifugation, filtration, or magnetic separation.
- 3 — Adds a release-and-recover step: treat the isolated complex to release the nucleic acid, then separate the released nucleic acid from the complex.
- 4 — The release in claim 3 is done with dilute alkali (specification: e.g., 0.5 M NaOH).
- 5 — The solid support of claim 1 is a beaded material.
- 6 — The bead is sepharose, agarose, or magnetic beads.
- 7 — The solid support of claim 1 is a polymer.
- 8 — That polymer support is shaped as a tube, dipstick, or microtiter plate.
- 9 — The solid support of claim 1 is a membrane.
- 10 — That membrane comprises nylon. (As published, claim 10 reads "The method of claim reagent of claim 9…" — another apparent typographical artifact; it depends from claim 9.)
Technical context (what the patent actually claims over the art)
The specification positions the invention against prior intercalator-on-support reagents — notably U.S. Pat. No. 4,119,521 (Chirikjian, 1978) (ethidium coupled to activated polysaccharide as a fluorescent stain) and the "Acrylamide-Ethidium" affinity medium of Vacek et al., Anal. Biochem. 124:414–420 (1982). The patent's own comparative Examples (Table I) argue the claimed methidium–spermine–sepharose reagent captures >90% of DNA even in untreated human serum and urine (where the acrylamide–ethidium reagent captured 0%), and binds >80% of DNA up to 3 M NaCl (where the acrylamide–ethidium reagent fell to as low as 12%). This salt-independence is expressly written into claim 1's "independent of the salt concentration" limitation.
Cited prior art (4 references): US 4,119,521 (Chirikjian); US 4,565,417 (Miles Labs); US 4,599,303 (HRI Associates); US 4,665,184 (Caltech — Dervan, bifunctional intercalator/EDTA molecules). Non-patent citations include Dervan & Becker, J. Am. Chem. Soc. 100:1968–1970 (1978) (the bis(methidium)spermine work), Sharp et al., Biochemistry 12:3055–3063 (1973), Thomas & Schechter, Anal. Biochem. 91:209–223 (1978), and Vacek et al. (1982).
Litigation / 2026 docket check
- Patent term: anticipated expiration 2007-07-29; status listed as Expired – Lifetime. Maintenance fees were paid (4th, 8th, 12th year) through the last recorded FPAY on 2001-11-01.
- CAFC 2026 dockets: my search returned no Federal Circuit 2026 appeal, no IPR/PGR, and no district court case referencing 4,921,805. The 2026 CAFC material surfaced (Headwater/Verizon, Wapp Tech/Apple, Teva v. Lilly, Ironburg v. Valve, etc.) involves unrelated patent numbers.
- Caveat: I could not query PACER/PTAB directly, so I cannot give a certified-clean litigation history. However, an expired-2007 patent would only be relevant today to historical damages within the § 286 six-year lookback, which closed no later than 2013 — so 2026 activity is not expected.
Uncertainty flags
- The "insulating" wording in claim 1(b) and the "claim reagent of claim 9" wording in claim 10 appear to be OCR/typographical artifacts, not substantive claim text. Flagged, not corrected.
- Google Patents lists the assignee as Life Technologies, Inc. and a "Related Parent" as US 07/078,991 (the abandoned 1987 application). The provided record shows priority date 1987-07-29 and filing date 1989-09-29; I have repeated those numbers literally as given.
- I have no authoritative information on any 2026 licensing, reassignment, or litigation involving this specific number beyond what is stated above.
Generated 9/27/2026, 8:02:19 PM
Cases on file (0)
Specific litigation cases in our database that name US patent 4921805. The free-form analysis below may also discuss cases beyond this list.
No cases on file mention this patent. Upload a CSV or add a case manually in Admin → Manage litigation cases.
Litigation summary
Past and pending lawsuits — plaintiffs, defendants, jurisdictions, outcomes, and notable rulings.
I'll search for litigation involving US patent 4921805 across patent litigation sources.
Let me search more targeted litigation databases for this specific patent.
Let me try a few more precise queries to be thorough.
Litigation Search Report — U.S. Patent No. 4,921,805
Bottom Line
No litigation, PTAB proceeding, ITC investigation, or Federal Circuit appeal involving U.S. Patent No. 4,921,805 ("Nucleic acid capture method") was found in any of the sources searched.
I cannot report a single case with plaintiff, defendant, jurisdiction, case number, filing date, and outcome, because no such case appears to exist in the public record I was able to reach. I am stating this as a negative finding rather than fabricating a docket entry.
What I Did Find (and why it is not responsive)
Searches for the literal string "4921805" produced only non-responsive hits. I list them so you can see the possible sources of confusion:
| Result | Why it is not the patent / case you asked about |
|---|---|
| US 9,492,180 — Rasmussen Instruments, LLC v. DePuy Synthes Products, Inc., No. 23-1855 (Fed. Cir. Oct. 6, 2025); D. Mass. No. 1:20-cv-11807-TSH | A different patent (knee-surgery instruments, inventor G. Lynn Rasmussen). The '180 shorthand refers to the last three digits of 9,492,180, not to 4,921,805. Unrelated technology, assignee, and parties. |
| JP Patent No. 4921805 (Seiko Instruments, angular-velocity sensor crystal vibrator) | A Japanese patent whose number happens to be 4921805. Different jurisdiction, subject matter, and owner. |
| Enzo Life Sciences v. Gen-Probe / Hologic / Becton Dickinson / Roche / Abbott (D. Del.) — the '180 patent = U.S. 6,992,180 | Again a "last-three-digits" collision. Enzo's asserted patents are 6,992,180 and 7,064,197 — not 4,921,805. |
| UK Gazette / Brazilian JUCI RS / SDC Security documents containing the digits "4921805" | Incidental numeric strings (insolvency notice numbers, company registration numbers, phone numbers). Not patents or cases. |
| Google Patents / FreePatentsOnline / uspto.report prosecution pages for US 4,921,805 | Bibliographic and prosecution data only, no litigation data. Notably, Google Patents' "Cited By" and "Similar Documents" lists show no litigation-based citations tied to this patent. |
Patent Background Relevant to a Litigation Search
Per the authoritative full text provided:
- Patent: US 4,921,805 A, "Nucleic acid capture method"
- Inventors: Gulilat Gebeyehu, Leonard Klevan, John D. Harding
- Assignee: Life Technologies, Inc. (original and current assignee)
- Priority date: 1987-07-29; Filed: 1989-09-29 (continuation of Ser. No. 07/078,991, filed July 29, 1987, now abandoned); Granted: 1990-05-01
- Legal status: Expired – Lifetime; anticipated expiration 2007-07-29
- Claims: 10 claims, drawn to a method of separating nucleic acids from an unpurified biological sample using a capture reagent (solid support + spermine/spermidine linker + methidium moiety)
The patent expired in 2007. Its ~17-year enforceable life (1989/1990–2007) significantly narrows the window in which infringement litigation could have been filed, which is consistent with the absence of hits.
Sources Searched and Limitations
- General web search engines queried for:
US patent 4921805 litigation lawsuit;"4921805" patent infringement case;"4,921,805" ... infringement;patent 4921805 "nucleic acid capture" litigation district court;unifiedpatents.com litigation 4921805. - Google Patents family/citation data for US 4,921,805 (which showed no litigation citations and a family of only US/EP/CA/JP, with "NON" family members besides US 4921805 and EP 0301899 / CA 1297432 / JP 1125395).
- Enzo Biochem SEC disclosures (referenced in results) — noted here only to rule out confusion with the unrelated Enzo '180 patent (U.S. 6,992,180).
Limitations you should weigh:
- I was unable to complete direct API-level queries to PACER, the Unified Patents litigation portal (
portal.unifiedpatents.com/litigation/caselist), Docket Alarm, or CourtListener before my tool budget was exhausted. My search results did surface a Unified Patents portal page and a Docket Alarm page, but neither showed a 4,921,805 case. - A true negative cannot be established with certainty from general web search alone; district-court complaints (especially pre-2000) are frequently not indexed in free databases.
- I found no evidence of any PTAB/IPR challenge (none would likely exist, as the patent expired in 2007) and no ITC Section 337 investigation.
Recommended Next Steps to Confirm the Negative
If you need a defensible "no litigation" conclusion for a clearance or diligence opinion, I suggest these targeted lookups (which I was unable to run to completion here):
- Unified Patents Litigation Portal — search the "Case List" / patent-number search for
4921805. - CourtListener / RECAP — docket search on patent number
4921805(and its reissue/continuation07/078,991). - PACER — party search for Life Technologies, Inc. and Bethesda Research Laboratories (BRL) as plaintiffs in the 1990–2007 window, filtering for patent cases.
- Lex Machina / Docket Navigator — these are the most reliable for a true negative, since they cover pre-2000 filings more completely than free sources.
- USPTO Patent Assignment / litigation history tabs and the USPTO Patent Litigation Docket dataset (public bulk data).
- Confirm whether the patent was ever the subject of a reissue or reexamination (the front page shows no reissue certificate).
Caveat on the "Strict Rule"
Per your instruction, I interpreted the identifier literally as U.S. Patent No. 4,921,805. I did not treat the search hits for 9,492,180, JP 4921805, or 6,992,180 as the same patent, because they are different patents. If, however, your underlying research question was actually about one of those similarly numbered patents, please confirm and I will pull the relevant case details (for example, the Rasmussen v. DePuy appeal is fully documented above, and the Enzo '180 patent litigations are well documented).
Conclusion: On the record available to me as of today's date, there is no known litigation involving US 4,921,805.
Generated 9/27/2026, 8:02:30 PM
Proceedings on file (0)
All PTAB activity →AIA trial proceedings (IPR / PGR / CBM) filed at the USPTO Patent Trial and Appeal Board against this patent. Sourced from the USPTO Open Data Portal and refreshed every six hours; each proceeding number deep-links to the PTAB E2E docket.
No PTAB proceedings on file. This patent has not been challenged via IPR, PGR, or CBM. The absence is itself a signal — well-asserted patents eventually attract IPRs. The LLM analysis below may surface filings the ODP feed hasn’t indexed yet.
PTAB challenges
AIA trial proceedings at the USPTO Patent Trial and Appeal Board — IPR, PGR, and CBM. Petitioners, judge panels, claim-level invalidation outcomes from Final Written Decisions, and Federal Circuit appeals. The single most important defensive datapoint after litigation history.
Proceedings overview
Zero AIA trial proceedings on file. The USPTO Open Data Portal returns no IPR, PGR, or CBM proceedings for US 4921805, and my independent web checks surfaced none — so the breakdown is 0 active / 0 claims invalidated / 0 claims sustained / 0 settled / 0 institution denials, and a defendant facing assertion today confronts a patent that has never been tested at the PTAB, but which expired on 2007-07-29 — meaning the practical defensive question is not "are the claims invalid" but "can this patent still be asserted at all."
No proceedings to report
Because the canonical structured block is empty and no proceeding numbers surfaced in search, I am not creating any ### {PROCEEDING_NUMBER} — {Petitioner} v. {Patent Owner} sections. I will not invent proceeding numbers to fill that template. If a proceeding exists that ODP has not yet indexed, it would be findable at the PTAB E2E system, and I found nothing there via search: https://ptacts.uspto.gov/
Confidence statement, stated plainly: I have high confidence that no IPR/PGR/CBM was ever instituted on this patent and moderate confidence that none was ever filed. My search reached indexed PTAB petition PDFs on PTAB E2E and PTAB-related aggregators, and no filing referenced 4921805 as the challenged patent. I cannot rule out a filing that was never publicly indexed (e.g., a petition denied pre-institution in a proceeding that predates full ODP indexing), but nothing I found supports one.
What I did confirm about the patent itself
- Patent: US 4921805 A, "Nucleic acid capture method"
- Inventors: Gulilat Gebeyehu, Leonard Klevan, John D. Harding
- Assignee: Life Technologies, Inc.
- Priority date: 1987-07-29 (application 07/078,991)
- Continuation filing: 1989-09-29 (application 07/414,728)
- Grant date: 1990-05-01
- Anticipated expiration: 2007-07-29
- Legal status: Expired – Lifetime
- Maintenance fees paid: 4-year (1993-11-01), 8-year (1997-10-27), 12-year (2001-11-01) — i.e., the full statutory term was paid, so the patent ran to term rather than lapsing for non-payment
- Granted claims: 10 (1 independent claim — claim 1 — with claims 2–10 depending from it)
Two claim-text cautions for anyone quoting this patent: the Google Patents OCR text of claim 1 reads "insulating said sample-capture reagent mixture," which is an OCR error for "incubating," and claim 10 reads "The method of claim reagent of claim 9," which is OCR-garbled. Quote from the USPTO Patent Public Search / Patent Center copy (https://patentcenter.uspto.gov/) or the granted patent PDF, not from scraped text.
Strategic summary
Claim status: all 10 claims WERE NEVER ADJUDICATED by the PTAB — every claim of 4921805 stands exactly as granted, but all of them are expired. There is no cancellation, no certificate, no estoppel. Claims 1–10 are "untested" on the PTAB axis and "sustained" only in the sense that no tribunal has killed them. The narrowing that did occur in this family was Canadian: the search surfaced CA1338207C / CA1297432C ("Nucleic acid capture reagent"), the Canadian counterparts, but I have not verified their prosecution outcomes and am not asserting them as narrowing events on the US claims.
Estoppel landscape: § 315(e)(2) is a non-issue here. Because no IPR was instituted, no petitioner is estopped from anything, and no district-court defendant is carrying IPR estoppel baggage. Conversely, that also means there is no FWD to point to and no claim-level invalidity holding to copy into a 2026 invalidity contention. Any invalidity theory you need today must be built from scratch in district court or a reexam-adjacent posture, not borrowed from an administrative record. Note also the statutory limits you'd face if you tried an AIA route: PGR is unavailable (the patent's 1987 priority date means it is not a first-inventor-to-file patent under AIA § 3(n)(1)), CBM is unavailable (program sunset 2020-09-16, and the patent is not a financial-services method patent), and IPR cannot reach § 112 grounds — only § 102/§ 103 on patents and printed publications.
Pattern signals: none. No repeat petitioner, no defensive aggregator (Unified Patents, RPX, etc.) has touched this patent — I searched the Unified Patents portal and found it indexing other Life Technologies documents (e.g., US 2003/0211489 A1), not this one. The patent owner has not pursued PTAB appeals on this patent because there is nothing to appeal. What the forward-citation record does show is that 4921805 became foundational prior art rather than a litigation asset: it appears in the "Cited By" list of well over a hundred later patents, including US 5,514,785 (Becton Dickinson), WO 1991/018996 / US 5,096,818 (Autogen Instruments), and it is cited as an X-category reference in EP 1627926 A1's partial European search report. In other words, the highest and best use of this document in 2026 is as an anticipation reference against third parties' later capture/hybridization claims — not as an assertion vehicle.
Recommended next steps
- If no assertion has actually occurred, say so and stop. The decisive fact for a defendant in 2026 is: the patent expired 2007-07-29, roughly 19 years ago. Damages under 35 U.S.C. § 286 reach back only six years from suit, so a suit filed today could at most reach conduct from 2020 onward — which is entirely after expiration. I am not aware of a live assertion of 4921805, and the structured PTAB data plus my search indicate the patent has not been litigated at the PTAB at all. Verify with a docket search before relying on the absence of litigation, since I did not run a full district-court docket sweep.
- If a demand letter cites US 4921805, the first response is expiration, not invalidity. Demand it be withdrawn on the ground that the patent's term ended 2007-07-29 and no pre-expiration damages window remains within § 286. Only if the sender identifies pre-2007 conduct should you invest in invalidity work.
- If you do need an invalidity position, do not look for a PTAB FWD — there is none. Build from the intrinsic record: the specification itself concedes the prior art (Chirikjian, US 4,119,521; Vachek et al., Anal. Biochem. 124:414–420 (1982); Thomas & Schechter, Anal. Biochem. 91:209–223 (1978); Dervan & Becker, JACS 100:1968–1970 (1978)), all four of which appear in the patent's own citations. Note the prosecution history and whether any of these were applied rather than merely listed — the answer matters for § 325(d)-style discretion if you ever do file an IPR, though given expiration an IPR is unlikely to be commercially worthwhile.
- No trial-stage milestones to track. There is no institution deadline, no oral hearing, and no statutory one-year FWD deadline running against this patent. The "absence of PTAB activity" signal here is not the usual one (an under-asserted patent); it is explained by expiration, and should be read that way rather than as evidence the claims are strong.
Verification links: patent record at https://patents.google.com/patent/US4921805/en and https://patentcenter.uspto.gov/; PTAB proceedings at https://ptacts.uspto.gov/; CAFC opinions at https://cafc.uscourts.gov/opinions-orders and https://www.courtlistener.com/?q=%224921805%22. I found no Federal Circuit appeal involving this patent, and no CourtListener or CAFC hit, which is consistent with there being no PTAB proceeding to appeal.
Generated 9/27/2026, 8:02:41 PM
Assignment history
Inventors, original assignee, and the chain of ownership recorded with the USPTO — including the correspondent attorney who recorded each assignment, since shell-LLC chains often share one repeat-player attorney even when the entity names look unrelated. Surfaces NPE / patent-troll patterns: shell-entity transfers, known asserters in the chain, repeat correspondent fingerprints, pre-litigation assignments, and bankruptcy fire-sales.
I'll reconstruct the assignment chain. Let me research the ownership record and corporate history.
Let me dig into the assignment records and the Life Technologies corporate chain.
Let me look for the actual recorded assignment reel/frame data for this patent.
Assignment & Ownership Chain — US 4,921,805
Scope note up front: I could not execute an interactive query against USPTO Assignment Center (https://assignmentcenter.uspto.gov/) or its mirror (https://assignment.uspto.gov/patent/index.html) with the tools available to me. I therefore report (a) the corporate chain of title, which is well-documented, and (b) only those record-level reel/frame entries I could corroborate from indexed sources. I have not fabricated any reel/frame numbers. Where I cannot cite a verified reel/frame for this patent, I say so explicitly rather than inventing one. This is itself a finding — see the Assignment Timeline.
Inventors
| Inventor | Residence of record | Employer at filing |
|---|---|---|
| Gulilat Gebeyehu | Silver Spring, Maryland | Life Technologies, Inc. (Bethesda Research Laboratories molecular-biology unit, Gaithersburg/Rockville, MD) |
| Leonard Klevan | Derwood, Maryland | Life Technologies, Inc. (same site) |
| John D. Harding | Potomac, Maryland | Life Technologies, Inc. (same site) |
- All three inventors' Maryland addresses are corroborated by the parallel European filing EP 0 301 899 ("Nucleic acid capture reagent"), applicant Life Technologies Inc., Gaithersburg, MD 20877, priority US 78991 (1987-07-29) — i.e., the same invention family as the 1989-09-29 US continuation.
- The three co-authored the underlying work (the "methidium–spermine–sepharose" DNA isolation chemistry appears in the Methods in Enzymology chapter by J. Harding et al. and in Nucleic Acids Res. (1989) by the same group, both citing this patent).
- Unusual patterns: none detected. There is no evidence of any inventor departing the assignee within 12 months of filing. All three are the assignee's own Gaithersburg research staff, and the patent was assigned to Life Technologies, Inc. from the outset. I could not verify individual employment end-dates, so I flag the departure question as not answerable from available records rather than negative.
Original assignee
Life Technologies, Inc. — the entity named on the issued patent (Google Patents "Original Assignee: Life Technologies Inc"; issue date 1990-05-01).
- History/business: formed 1983 by the merger of GIBCO Corp. (then a subsidiary of Dexter Corp.) and Bethesda Research Laboratories (BRL). Headquarters moved to Gaithersburg/Rockville, Maryland. Primary line of business: life-science research reagents — cell-culture media/sera (GIBCO brand) and molecular-biology reagents and enzymes (BRL brand).
- Did it ship a product embodying the claims? Yes, in substance. The claimed methidium–spermine–sepharose capture reagent is the same chemistry the inventors published as a Methods in Enzymology protocol, and Life Technologies built a nucleic-acid isolation product line (BRL molecular-biology reagents) plus a non-isotopic HBV/HPV detection program around it — the 1987 Toray licensing agreement and the 1989 FDA clearance of the HPV test were the commercial vehicles. (Note: the molecular diagnostics division was sold in December 1990 for $3.6 M, i.e., the diagnostic downstream, not the reagent chemistry.)
- Current status: no longer an independent entity. Invitrogen Corp. completed its ~$1.9 B acquisition of Life Technologies and its majority owner Dexter Corp. on 2000-09-14; the "Life Technologies" name was discontinued. The name was revived in November 2008 for the Invitrogen + Applied Biosystems combination (Life Technologies Corporation), which was in turn acquired by Thermo Fisher Scientific in 2014. So the line of title today, if intact, sits with Life Technologies Corporation, a wholly-owned Thermo Fisher Scientific Inc. subsidiary.
Contradiction flag (carried from the prior section): Google Patents' "Current Assignee" field still displays "Life Technologies Inc." That field is a normalized echo of the original assignee and is not evidence of a separate recorded assignment. It is inconsistent with the corporate record (which points to Life Technologies Corporation / Thermo Fisher) and should be treated as a data artifact, not title.
Assignment timeline
Critical finding: The Google Patents legal-events table for US 4,921,805 contains no assignment ("AS") events whatsoever — only STCF (1990-02-28 patent grant), FPAY (1993-11-01), FPAY (1997-10-27), and FPAY (2001-11-01). No chain-of-title recordation is exposed against this patent number in any indexed source I could reach. The items below therefore separate verified reel/frame evidence from corporate-transaction evidence with the reel/frame unretrieved.
1987 (executed, on/before the 1987-07-29 priority filing) / recorded c. 1987–1988 — Reel/Frame: NOT RETRIEVED
- Conveyance: Assignment (inventor-to-company)
- Assignor: Gebeyehu, Klevan, and Harding
- Assignee: Life Technologies, Inc.
- Correspondent: not retrievable (no record exposed)
- Context: routine employee invention assignment. Not verified against a record; inferred from the fact that the patent issued with Life Technologies as assignee and no inventor-owned period is reflected anywhere.
2000-09-14 (executed — Invitrogen/Dexter/Life Technologies merger closes) / recording date NOT RETRIEVED — Reel/Frame: NOT RETRIEVED for this patent
- Conveyance: Merger
- Assignor: Life Technologies, Inc.
- Assignee: Invitrogen Corporation (Carlsbad, CA)
- Correspondent: not retrievable
- Context: acquisition (Invitrogen buys Life Technologies + Dexter for ~$1.9 B). Title passed by operation of law on the merger; no operating change to the reagent business.
- Partial corroboration: an INPADOC
ASevent on a sibling Life Technologies patent shows a "NEW OWNER: INVITROGEN CORPORATION, CALIFORNIA" record, confirming this transfer was recorded as a block across the Life Technologies portfolio. The specific reel/frame was not exposed for 4,921,805.
2008-11-21 (executed) / recorded 2010-02-03 — Reel 023882 / Frame 0551
- Conveyance: Merger (
MERGER; ASSIGNOR: INVITROGEN CORPORATION) - Assignor: Invitrogen Corporation
- Assignee: Life Technologies Corporation (Carlsbad, CA)
- Correspondent: not retrievable
- Context: internal reorg / change of name — "LT Name Corporation" merged into Invitrogen Corporation (effective 2008-11-21), Invitrogen as survivor was renamed Life Technologies Corporation, concurrent with the Applied Biosystems acquisition.
- Important qualification: reel 023882/0551 is the blanket portfolio merger recording. I could not confirm it was recorded against 4,921,805 specifically, and a later corrective filing (below) shows this reel was over-inclusive.
- Conveyance: Merger (
2014-11-14 (recorded) — Reel 034217 / Frame 0490
- Conveyance: Correction (corrective assignment)
- Assignor / Assignee: Life Technologies Corporation / Life Technologies Corporation
- Correspondent: not retrievable
- Context: housekeeping — expressly "CORRECTIVE ASSIGNMENT TO CORRECT THE APPLICATION NO … PREVIOUSLY RECORDED ON REEL 023882 FRAME 0551… THE MERGER SHOULD NOT HAVE BEEN RECORDED AGAINST THIS PATENT APPLICATION NUMBER." This confirms the 023882/0551 merger reel was applied over-inclusively and later pruned.
- (These two reel/frame pairs — 023882/0551 and 034217/0490 — are verified from indexed INPADOC legal-status data for a sibling Life Technologies filing, not from a 4,921,805 record. I present them as the identifiers of the portfolio-wide merger and its correction, and flag that attribution to this patent is unconfirmed.)
2014-02-03 (Thermo Fisher Scientific completes acquisition of Life Technologies Corporation)
- Conveyance: Acquisition / change of corporate parent (no separate recorded assignment exposed for this patent)
- Assignor: Life Technologies Corporation shareholders
- Assignee: Thermo Fisher Scientific Inc. (Life Technologies Corporation continued as a wholly-owned subsidiary, so title likely never left the named entity)
- Context: acquisition. By this date the patent had already expired (2007-07-29), so this and item 4 are title housekeeping with no residual right to convey.
Because the Assignment Center returned nothing usable for this patent number, I am stopping the record-level reconstruction here and stating plainly: as far as exposed records show, this patent carries only its original assignment, with all subsequent transfers flowing from corporate mergers/name changes rather than from a patent-level assignment agreement.
Timeline diagram
timeline
title Ownership of US 4921805
1987 : Inventors assign to Life Technologies Inc
1990 : Patent issued to Life Technologies Inc
2000 : Invitrogen acquires Life Technologies and Dexter
2007 : Patent expires
2008 : Invitrogen renamed Life Technologies Corporation
2014 : Life Technologies acquired by Thermo Fisher
NPE / troll-pattern signals
- Shell-entity transfer — Not present. No record of any transfer to an "IP / Patents / Licensing / Holdings / Ventures" entity. The only recorded/verified links are reel 023882/0551 (Invitrogen → Life Technologies Corporation) and reel 034217/0490 (correction) — both plain corporate mergers, no LLC intermediary, no registered-agent address.
- Known asserter in the chain — Not present. No assignee in the chain (Life Technologies, Inc. → Invitrogen Corporation → Life Technologies Corporation → Thermo Fisher Scientific) matches any public NPE list (Acacia, Marathon, IV, IPNav, Wi-LAN, Mosaid/Conversant, Vringo, Pendrell, Innovatio, MPHJ, Lumen View, Round Rock, Erich Spangenberg entities, etc.). All are/were operating life-science companies.
- Repeat correspondent across the chain — Unclear. Correspondent data is not exposed in any source I could reach for this patent. I cannot confirm or rule out a single filing agent spanning the recordings, and I will not assert recurrence I cannot document.
- Cascading transfers (<24 months through chained LLCs) — Not present. The chain's recorded transfers are spaced 2000 → 2008 → 2014, and none involve LLCs.
- Pre-litigation transfer — Not present. No infringement suit naming 4,921,805 appears in any record reviewed (consistent with the prior section's finding of no 2026 and no historic litigation); there is therefore no pre-suit assignment to match against.
- Bankruptcy fire-sale — Not present. Life Technologies and Dexter were acquired through a contested but solvent deal (Invitrogen outbid International Specialty Products; ISP later sought an appraisal in Delaware Chancery, which is a valuation dispute, not a bankruptcy). The only divestiture near the relevant period was the Dec-1990 sale of the molecular diagnostics division for $3.6 M — a business-unit sale, not a Chapter 7/11 patent auction.
- Privateering — Not present. No evidence in SEC filings or third-party coverage that any chain entity transferred this patent to an NPE to assert on its behalf. The 1990 Enzo v. Life Technologies-type disputes touch other patents in the field, not this one.
- Defensive aggregator (anti-NPE) — Not present. The chain does not terminate at RPX, AST, LOT, Unified Patents, or OIN. It terminates inside Thermo Fisher Scientific.
Verdict
Defensive / non-asserting.
Of the five permitted labels this is the closest fit, and I am choosing it on substance rather than on the label's parenthetical: the patent is expired as of 2007-07-29 (20 years from the 1987-07-29 earliest US filing date, per the URAA transitional rule — matching Google's "anticipated expiration 2007-07-29" and the final FPAY maintenance payment recorded 2001-11-01), it has never been asserted, and 100% of the chain of title sits with operating life-science companies — original assignee Life Technologies, Inc., then Invitrogen Corporation (2000-09-14 merger), then Life Technologies Corporation (reel 023882/0551, recorded 2010-02-03, corrected at reel 034217/0490 on 2014-11-14), now under Thermo Fisher Scientific (2014). Caveat I want to be explicit about: the chain does not terminate at a formal defensive aggregator (RPX / AST / LOT / Unified), so the parenthetical gloss on this category does not literally apply — no category in the menu cleanly describes "operating-company-owned, expired, never asserted." I flag that mismatch rather than pretending it fits.
Verification links: USPTO Assignment Center — https://assignmentcenter.uspto.gov/ (search by patent number 4921805); mirror — https://assignment.uspto.gov/patent/index.html. Google Patents legal events (shows only STCF + three FPAY, no assignment records) — https://patents.google.com/patent/US4921805/en.
Residual uncertainty: If the Assignment Center does surface an AS entry for this patent that I could not reach, the most likely candidates are (i) the original 1987–88 inventor assignment and (ii) the 2000 Life Technologies → Invitrogen merger record; neither would change the verdict, because both assignees are operating companies and the patent expired in 2007.
Generated 9/27/2026, 8:03:13 PM
Prior art
Earlier patents, publications, and products that may anticipate or render the claims unpatentable.
I'll search for the specific patent and its prior-art citations.
Let me pull the remaining cited references.
Prior-Art Analysis — U.S. Patent No. 4,921,805 ("Nucleic acid capture method")
Scope note: This builds on the bibliographic and litigation sections already generated (patent = US 4,921,805 A, Life Technologies, Inc.; inventors Gebeyehu/Klevan/Harding; effective filing date 1987‑07‑29 via parent Ser. No. 07/078,991; granted 1990‑05‑01). I do not repeat that material. Source for the record: https://patents.google.com/patent/US4921805/en and https://uspto.report/patent/grant/4921805 — I did not query the USPTO Patent Public Search API directly, so the citation list below is taken verbatim from the "Patent Citations (4)" and "Non-Patent Citations (11)" tables of the authoritative text provided, which mirror the USPTO front page.
1. Identification of the patent (literal-number confirmation)
The record at US 4,921,805 is confirmed as "Nucleic acid capture method." The face of the patent lists exactly four (4) U.S. patent citations (all marked cited by examiner) and eleven (11) non-patent citations (several of which are duplicate listings of the same paper). No similar-numbered documents (e.g., JP 4921805, US 9,492,180, US 6,992,180) are treated here; those are unrelated and are excluded per the strict-identifier rule.
2. The four patent citations (face of US 4,921,805)
Reference A — U.S. Pat. No. 4,119,521 (Chirikjian)
| Field | Value |
|---|---|
| Title | Fluorescent derivatives of activated polysaccharides |
| Inventor | Jack G. Chirikjian (assignee of record rendered as "Stephen Turner" on the Google Patents family line; inventor confirmed as Chirikjian) |
| Filed | 1977‑04‑25 |
| Issued | 1978‑10‑10 |
| URL | https://patents.google.com/patent/[US4119521A](/patent/US4119521A)/en ; https://www.freepatentsonline.com/4119521.html |
Description: Discloses a fluorescent DNA-intercalating agent (an ethidium halide, preferably ethidium bromide; acridine derivatives also named) covalently coupled to an activated, water‑insoluble polysaccharide — e.g., cyanogen‑halide‑activated agarose / "CNBr‑activated Sepharose 4B" (Sephadex also named). The derivative is admixed into electrophoretic gels and used as a fluorescent stain so that DNA bands can be visualized under short‑wave UV. There is no capture, no wash, no release, and no linker between intercalator and support (coupling is direct to the activated polysaccharide).
§102 relevance: This is the closest patent art for the bare concept "intercalator‑on‑solid‑support," and it is §102(b) art (issued >1 yr before the 1987‑07‑29 critical date). However, it does not anticipate any of claims 1–10:
- Intercalator is ethidium, not methidium (claim 1 requires a methidium moiety).
- No spermine/spermidine linker — coupling is direct to activated agarose.
- Use is gel staining, not capture/separation of nucleic acids from an unpurified biological sample.
- Nothing about salt-independent binding.
Potentially anticipatory of: none of claims 1–10 as written. Best characterized as §103 art.
Reference B — U.S. Pat. No. 4,565,417 (Miles Laboratories, Inc.)
| Field | Value |
|---|---|
| Title | Nucleic acid hybridization assay employing antibodies to intercalation complexes |
| Inventors | James P. Albarella et al. |
| Filed | 1984‑08‑31 (priority US 560,429, 1983‑12‑12) |
| Issued | 1986‑01‑07 |
| URL | https://patents.google.com/patent/[US4563417](/patent/US4563417) |
Description: Hybridization assays in which a nucleic-acid intercalator (ethidium, acridines, proflavin, etc. — a long list) binds to duplex DNA formed between probe and target, creating an intercalation complex that is detected by an anti-intercalation-complex antibody. The intercalator is used free in solution as a reporter/immunogenic modifier; one embodiment contemplates immobilizing a probe on a solid support.
§102 relevance: §102(b) art. It is not directed to a capture reagent of intercalator‑linker‑solid support, discloses no methidium and no spermine/spermidine linker, and does not address salt-independent capture from unpurified samples. Anticipates none of claims 1–10; useful only as background/obviousness art.
Reference C — U.S. Pat. No. 4,599,303 (HRI Associates, Inc.)
| Field | Value |
|---|---|
| Title | Nucleic acid hybridization assay employing probes crosslinkable to target sequences |
| Inventors | Kenichi K. Yabusaki; Howard B. Gamper, Jr.; Stephen T. Isaacs |
| Filed | 1983‑12‑12 (some records: priority 1983‑12‑11) |
| Issued | 1986‑07‑08 |
| URL | https://patents.google.com/patent/[US4599303A](/patent/US4599303A)/en ; https://portal.unifiedpatents.com/patents/patent/US-4599303-A |
Description: Uses probes bearing crosslinkable intercalating moieties (e.g., psoralens such as AMT/4,5′,8‑trimethylpsoralen) that, upon hybridization, form covalent bonds to the target; labels/ligands allow amplification and detection. Solid-support formats are contemplated.
§102 relevance: §102(b) art (issued 1986‑07‑08, which is more than one year before the 1987‑07‑29 effective filing date). It is about crosslinking probes, not about a methidium‑linker‑solid‑support capture reagent, and does not disclose salt-independent capture from serum/urine/cervical samples. Anticipates none of claims 1–10.
Reference D — U.S. Pat. No. 4,665,184 (California Institute of Technology — Dervan et al.)
| Field | Value |
|---|---|
| Title | Bifunctional molecules having a DNA intercalator or DNA groove binder linked to ethylene diamine tetraacetic acid |
| Inventors | Peter B. Dervan et al. |
| Filed | 1983‑10‑12 |
| Issued | 1987‑05‑12 |
| URL | https://patents.google.com/patent/[US4665184A](/patent/US4665184A)/en |
Description (the chemically closest U.S. patent): Discloses bifunctional molecules in which a DNA intercalator — expressly including "p‑carboxy methidium" and "p‑carboxy ethidium" — is tethered through a short linker (1,3‑diaminopropane / "propyl") to the metal chelator EDTA (→ methidium‑propyl‑EDTA, "MPE"). The compounds are used to cleave DNA (with Fe(II)/O₂), not to capture it. Notably, the p‑carboxy methidium halide starting material disclosed here is the same intermediate the '805 specification uses to build its reagent.
§102 relevance: Because it issued 1987‑05‑12 — within one year of the 1987‑07‑29 critical date — it is not §102(b) art. It is, however, available as §102(a) art (known/invented by others before the applicant's invention) and, more significantly, as §102(e) art (U.S. patent granted on an application filed 1983‑10‑12, i.e., before applicant's invention). Anticipation analysis:
- It discloses a methidium intercalator + a short diamine-type linker — the two of the three capture-reagent components.
- It does not disclose a solid support, does not disclose spermine or spermidine, and is not a method of separating nucleic acids from an unpurified biological sample with isolation of a capture‑reagent/nucleic‑acid complex.
Potential anticipation: a hypothetical product claim to "methidium linked to a diamino linker" might be arguable, but claims 1–10 (method claims) are not anticipated by '184. It is best treated as the primary §103 reference for the methidium‑plus‑linker concept.
3. Non-patent citations (face of the patent)
The eleven listed non-patent items collapse to six distinct references (several appear twice in the OCR'd list):
| # | Citation | Distinct content & §102 role |
|---|---|---|
| 1 | Dervan, P.B. & Becker, M.M., J. Am. Chem. Soc. 100:1968–1970 (1978) ("Molecular Recognition of DNA by Small Molecules. Synthesis of Bis(methidium)spermine…") | The single most chemically relevant prior art. Discloses bis(methidium)spermine — two methidium intercalators joined by a spermine linker. This is the direct source of the claimed methidium + spermine combination. But it is a polyintercalator compound, with no solid support and no capture/separation method. Printed publication, dated well before 1986‑07‑29 → §102(b) art. Anticipates no method claim (no support, no isolating step), but is critical §103 art. |
| 2 | Vacek, A.T. et al., Anal. Biochem. 124:414–420 (1982) ("ethidium‑acrylamide affinity medium") | The most relevant method art: an intercalator (ethidium) immobilized on a solid matrix (acrylamide) used to recover nucleic acids from solution and from gels. But: ethidium (not methidium), acrylamide/methylenebisacrylamide spacer (not spermine/spermidine), and it loses binding at ≥1 M NaCl — i.e., the opposite of the claimed salt independence. §102(b) art. Anticipates no claim; the '805 specification itself uses Vacek as the comparative foil (Table I). |
| 3 | Thomas, K.A. & Schechter, A.N., Anal. Biochem. 91:209–223 (1978) | Ethidium covalently linked to agarose via a 3,3′‑diaminodipropylaminosuccinyl spacer, studied for tRNA (nucleic acid) binding; shows intercalative binding and that binding drops to ~0% at ≥1.3 M NaCl. §102(b) art. Closest to "intercalator‑linker‑solid support binding nucleic acid," but ethidium (not methidium), a diaminodipropyl (not spermine/spermidine) linker, a binding study rather than a separation method, and salt-sensitive. Anticipates no claim. |
| 4 | Sharp, P.A. et al., Biochemistry 12:3055–3063 (1973) | Ethidium‑bromide staining of DNA in agarose gels. Pure background; anticipates nothing. |
| 5 | *Barry et al., J. Chem. Soc. (Dalton Trans.), p. 2086 (1974)* | Metal‑coordination/chemistry paper (examined for intercalator chemistry background). No capture method. |
| 6 | Kimberly & Goldstein, Anal. Chem. 53:789 (1981) | Analytical‑chemistry paper on immobilized/derivatized supports. No methidium capture method. |
4. Anticipation (§102) assessment — summary
Section 102 requires a single reference disclosing every element of a claim. The claim 1 conjunctive elements are: (i) solid support; (ii) spermine or spermidine linker bound to the support; (iii) methidium moiety bound to the linker; and (iv) the method steps of contacting an unpurified biological sample, incubating to form a capture‑reagent–nucleic‑acid complex, and isolating that complex — with salt‑independent binding. No single cited reference supplies all of these.
| Cited reference | §102 status | Claim 1 fully anticipated? | Any claim anticipated? | Why not |
|---|---|---|---|---|
| US 4,119,521 (Chirikjian) | §102(b) | No | None | Ethidium not methidium; no spermine/spermidine; staining use, not capture from biological sample |
| US 4,565,417 (Miles/Albarella) | §102(b) | No | None | Free‑solution intercalator + antibody detection; no solid‑support capture reagent |
| US 4,599,303 (HRI/Yabusaki) | §102(b) | No | None | Crosslinkable/psoralen probes, not methidium‑linker‑support capture |
| US 4,665,184 (Caltech/Dervan) | §102(a)/(e) (not (b)) | No | None (method claims) | Discloses methidium + short diamine linker to EDTA, but no solid support and no separation method |
| Dervan & Becker 1978 (BMSp) | §102(b) | No | None | Methidium + spermine, but as a bis‑intercalator compound; no support, no method |
| Vacek et al. 1982 | §102(b) | No | None | Ethidium‑acrylamide; no methidium/spermine; salt‑sensitive, not a §102 match |
| Thomas & Schechter 1978 | §102(b) | No | None | Ethidium‑agarose spacer; binding study, salt‑sensitive, no methidium/spermine |
| Sharp 1973; Barry 1974; Kimberly & Goldstein 1981 | §102(b) | No | None | Background/staining/analytical chemistry |
Independent-claim result: None of the four patent citations, and none of the non‑patent citations, anticipates claim 1 (hence none anticipates dependent claims 2–10, all of which incorporate claim 1's elements; claims 2, 5–10 merely recite isolation means or support formats routinely known in the art, and claims 3–4 add a NaOH-release step).
Closest art / best §103 combination (for completeness, though outside the strict §102 question):
- Dervan & Becker (1978) or Dervan '184 supplies methidium + spermine/diamine linker.
- Chirikjian '521, Thomas & Schechter (1978), or Vacek (1982) supplies intercalator immobilized on a solid support for nucleic‑acid binding/recovery.
- Neither supplies the synergistic, claimed salt‑independent capture from raw serum/urine/cervical samples, which the '805 specification uses (Table I: >90% capture in untreated serum/urine with methidium‑spermine vs. ~0–8% for acrylamide‑ethidium; >80% binding to 3 M NaCl) as its principal non‑obviousness showing.
5. Caveats and honesty flags
- No full §102 anticipation by any cited reference. I am stating this as a negative finding based on element‑by‑element comparison against claim 1; I did not find any cited reference that discloses all of (i)–(iv). An anticipation rejection on these four references would not be sustainable as to claim 1.
- The most dangerous reference is not a U.S. patent — it is Dervan & Becker, JACS 100:1968 (1978) (methidium‑spermine) in combination with an intercalator‑on‑support reference (Chirikjian '521 / Thomas & Schechter 1978 / Vacek 1982). This is a §103, not §102, posture.
- Date subtleties: US 4,599,303 (1986‑07‑08) and the three earlier patents are §102(b) art relative to the 1987‑07‑29 critical date; US 4,665,184 (1987‑05‑12) is not §102(b) but remains available under §102(a)/(e) because its application was filed 1983‑10‑12.
- OCR caveats carried forward: the published claim renders 1(b) as "insulating" (clearly "incubating") and claim 10 as "claim reagent of claim 9"; these do not affect the prior‑art analysis.
- I did not independently verify the exact inventor/assignee string for US 4,119,521 (the Google Patents family line associates a "Stephen Turner" name string with the assignee field while the patent names Chirikjian as inventor); the substantive disclosure description above is drawn from the patent's own text and is unaffected by that discrepancy.
- No reissue or reexamination is reflected on the front page; the citation set above is the complete examiner‑cited art of record.
Bottom line: The examiner cited four U.S. patents and a short list of journal articles. The single most relevant reference to the inventive core of US 4,921,805 (methidium + spermine linker) is the Dervan & Becker 1978 bis(methidium)spermine paper, but no cited reference — patent or non‑patent — anticipates claim 1 or any of claims 2–10 under §102; the art is properly an obviousness (§103) question.
Generated 9/27/2026, 8:03:08 PM
Obviousness
Combinations of prior art that suggest the claimed invention would have been obvious under 35 U.S.C. § 103.
I'll ground the prior-art characterizations before building the § 103 analysis.
Obviousness Analysis — U.S. Patent No. 4,921,805 under 35 U.S.C. § 103
Analysis date: April 26, 2026. This builds on, and does not repeat, the claim charting and bibliographic work in the prior summary/litigation sections. All references discussed are drawn from the "Cited Prior Art / Non-Patent Citations" fields of the patent page (https://patents.google.com/patent/[US4921805](/patent/US4921805)/en), and their content is confirmed below by independent sources where available.
1. Bottom line
The claims of US 4,921,805 are, in my assessment, vulnerable to a § 103 challenge, but the strength of the challenge is uneven:
| Claim(s) | Obviousness exposure | Comment |
|---|---|---|
| 2, 5–10 (support format / isolation mechanics) | High — near-certain | Purely conventional format and separation choices; each is expressly disclosed in the cited art or is routine laboratory practice |
| 3–4 (release with dilute alkali) | High | Elution/recovery of captured nucleic acid was the whole point of Thomas & Schechter and Vacek; alkali is a routine alternative eluant |
| 1 (the sole independent claim) | Moderate | The structure (methidium + spermine/spermidine + support) is squarely suggested by combining the cited references; the contest is over the "independent of the salt concentration" functional limitation and the applicants' comparative Table I data |
The single point of genuine novelty over the art as the examiner saw it is the salt-independence limitation. Everything else in claim 1 is a combination of elements the art already had.
2. Legal framework applied
Under Graham v. John Deere Co., 383 U.S. 1 (1966), I consider (i) the scope and content of the prior art, (ii) the differences between the prior art and the claims, (iii) the level of ordinary skill, and (iv) secondary considerations. Under KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007), a claim is obvious where the combination of known elements yields no more than predictable results, where a known element is substituted for another to obtain a predictable result, or where the combination is "obvious to try" from a finite set of identified, predictable solutions. The motivation to combine need not be found in a single reference; it may come from the knowledge of a person having ordinary skill in the art (PHOSITA), the nature of the problem, or the teachings of the references collectively (In re Keller). A reference that merely discloses an alternative does not teach away unless a PHOSITA would be discouraged from following the claimed path.
Level of ordinary skill in the art (1987): a molecular biologist or bio-organic chemist with an advanced degree and several years' experience in nucleic-acid affinity separation and bioconjugation — i.e., someone comfortable with CNBr-activated Sepharose, carbodiimide/NHS coupling, and intercalator chemistry.
Reference dates (pre-AIA): Sharp (1973), Chirikjian US 4,119,521 (1978), Dervan & Becker (1978), Thomas & Schechter (1978), Vacek (1982), Miles US 4,565,417 (1986) and HRI US 4,599,303 (1986) all predate the 1987-07-29 priority date by more than a year and are § 102(b) art. Dervan/Caltech US 4,665,184 (filed 1983-10-12; issued 1987-05-12) is § 102(e)/§ 103 art as of its filing date. All are available as § 103 prior art.
3. Claim 1 element-by-element against the prior art
| Claim 1 element | Prior-art disclosure | Source |
|---|---|---|
| (i) Solid support | Agarose/Sepharose 4B beads (Chirikjian; Thomas); polyacrylamide beads, Bio-Gel P-4 (Vacek) | US 4,119,521; Thomas & Schechter 1978; Vacek 1982 |
| (ii) Linker bound to support, comprising spermine or spermidine | Spermine expressly used as the methidium-to-methidium linker, chosen "because of its known affinity for nucleic acid and its length" (Dervan & Becker). Structurally, Thomas uses a 3,3′-diaminodipropylamine (DAPA)–succinyl spacer — a spermine/spermidine homolog fragment — to tether ethidium to agarose | Dervan & Becker, JACS 100:1968–70 (1978); Thomas & Schechter, Anal. Biochem. 91:209–23 (1978) |
| (iii) Methidium moiety bound to linker | Methidium is the intercalator of Dervan & Becker's bis(methidium)spermine (BMSp) and of Dervan's methidium-EDTA (MPE) constructs | Dervan & Becker 1978; US 4,665,184 (Dervan) |
| Intercalator binds nucleic acid by intercalation | Established for ethidium-on-support by Thomas & Schechter (fluorescence + spectral proof of intercalation) and for methidium generally | Thomas & Schechter 1978; Vacek 1982 |
| Unpurified biological sample | Intercalation-based detection/hybridization assays were already applied to clinical specimens | US 4,565,417 (Miles); US 4,599,303 (HRI) |
| Contact → incubate → isolate complex | The essential workflow of affinity capture: load sample, allow equilibration (Vacek: "15 min to assure quantitative binding"), elute | Vacek 1982; Thomas & Schechter 1978 |
Nothing in claim 1's three-step method was novel as a method concept — intercalator-on-support capture of nucleic acids from solution was Thomas & Schechter's stated subject matter and Vacek's explicit purpose ("recovery of nucleic acids from free solution and from … gels"). The novelty resides almost entirely in the identity of the intercalator/linker pair (methidium–spermine) and the salt-independence functional limitation.
4. The combinations that render the claims obvious
Combination I (primary, strongest): Thomas & Schechter ’78 + Dervan & Becker ’78 (+ Dervan US 4,665,184)
- Thomas & Schechter disclose the complete capture architecture: an intercalator covalently attached through an amine/succinyl spacer to Sepharose 4B beads, binding tRNA by intercalation, and fractionating nucleic acids on that support by salt-gradient elution. This is a nucleic-acid capture reagent in everything but name.
- Dervan & Becker disclose the exact structural advance the claim needs: replacing a simple intercalator/spacer with methidium joined through a spermine linker, and they expressly state the resulting bis-intercalator binds DNA with a constant several orders of magnitude higher than ethidium.
- Substituting the methidium–spermine intercalator/linker pair into Thomas & Schechter's support-bound architecture is the classic KSR "substitution of one known element for another to obtain a predictable result."
Motivation: the problem the applicants themselves identify — escaping phenol, CsCl gradients, and protein co-precipitation for clinical samples — was a known, long-felt need; affidavits of skill in the art would support that a PHOSITA seeking a more robust capture reagent would look to the highest-affinity intercalator-linker pair available, and Dervan & Becker supplies it. Dervan's own rationale (spermine's nucleic-acid affinity and length) supplies the reason to keep the spermine linker when moving methidium onto a support.
Combination II (Vacek ’82 + Dervan & Becker ’78)
Vacek is arguably the closest art because it is purposive: the ethidium–acrylamide medium exists specifically to capture/immobilize nucleic acids from solution and to recover them (elution with 1 M NaCl), with capacity measurements on calf-thymus DNA and rRNA. Its only deficiencies relative to claim 1 are (a) ethidium instead of methidium and (b) an acrylamide matrix with a methylenebisacrylamide spacer. Dervan & Becker supplies (a); the support choice in (b) is a routine substitution (Chirikjian had already used Sepharose). Thus Vacek + Dervan & Becker ≈ the claimed method.
Combination III (Chirikjian ’521 + Vacek ’82 + Dervan & Becker ’78)
Chirikjian teaches ethidium covalently coupled to CNBr-activated Sepharose 4B — i.e., the intercalator-support conjugate and its preparation — and confirms the coupling chemistry is routine. Vacek supplies the capture/elute utility. Dervan & Becker supplies methidium–spermine. Three references, but each contributes a discrete, non-overlapping teaching, satisfying In re Keller.
Secondary references supplying the "unpurified biological sample" motivation
To the extent the claim's "unpurified biological sample" limitation is treated as a separate hurdle, US 4,565,417 (Miles, antibodies to intercalation complexes) and US 4,599,303 (HRI, crosslinkable intercalator-derived probes) demonstrate that intercalator/nucleic-acid chemistry was already being used directly on clinical samples and hybridisation formats. A PHOSITA designing a clinical capture reagent would have been motivated to make the support-bound reagent work in serum/urine rather than only in buffers and gels.
5. The crux: "independent of the salt concentration of said sample"
This is the only limitation with a real nonobviousness argument, and it cuts both ways.
Why it does not save the claim (the obviousness case):
- The property is a predictable consequence of the known structure. Dervan & Becker chose spermine precisely because it is a polyamine with high nucleic-acid affinity; the specification itself concedes that polyamines such as spermine/spermidine are "positively charged at their internal secondary amines near neutral pH." A PHOSITA would expect a tetracationic polyamine tether, combined with an intercalator of far higher intrinsic affinity, to retain binding at higher ionic strength than a mono-cationic ethidium tethered by a short neutral spacer. The claimed result (better salt tolerance) follows in kind from a known property difference.
- Inherency. Where a claimed property is inherent in the structure produced by the prior art, that property generally cannot confer patentability over that structure or the obvious method of using it (In re Best). If methidium–spermine–support inherently binds DNA with reduced salt sensitivity, the functional language does not patentably distinguish the obvious combination.
- Vacek gives a comparative baseline showing the direction of improvement was recognized. Vacek's medium is eluted with 1 M NaCl, i.e., the art already understood the intercalator–nucleic-acid interaction as a salt-controlled equilibrium and manipulated it deliberately. Thomas & Schechter went further and quantified it (dissociation as a function of NaCl; ~1.3 M giving ~0% binding). One of skill reading these is handed both the variables (intercalator identity, linker charge/length) and the design rule.
Why it nevertheless resists the rejection (the applicant's best argument):
- Thomas & Schechter is, on its face, a teaching away: for a Sepharose-bound intercalator, raising NaCl abolished binding. A PHOSITA could read this as a general limitation of support-bound intercalators and be discouraged from claiming a support-bound reagent that works across 0–3 M salt and in undiluted serum.
- The applicant's Table I is real, comparative, and dramatic: the acrylamide–ethidium reagent captured 0% in treated or untreated serum and fell to as low as 12% at 3 M NaCl, whereas methidium–spermine captured >90% in serum/urine and 82–99% across 0–3 M NaCl. On a Wm. Wrigley/"unexpected results" theory, a difference of this magnitude — a reagent that fails entirely in the very samples the invention targets versus one that works — could be argued to be a difference in kind, not merely degree. That the ethidium leached off the acrylamide matrix in serum (a stability failure the applicants expressly noted) sharpens the argument.
My assessment: a court or the PTAB would likely find claim 1 prima facie obvious over Thomas & Schechter (or Vacek) + Dervan & Becker, and would then have to decide whether Table I rebuts it. The rebuttal is genuinely contestable because the applicants' own specification supplies the mechanistic explanation (cationic linker) that makes the result appear predictable, and because Dervan & Becker already told the reader the affinity difference was orders of magnitude. I would put claim 1 at roughly 60–65% likelihood of being held invalid on this record — closer than the dependent claims, but leaning obvious. That is a far cry from a certainty, and the case is one where a skilled advocate could go either way.
6. Dependent claims 2–10
These fall with even less resistance:
- Claim 2 (centrifugation / filtration / magnetic separation): mechanical separation of a bead-supported complex is routine; Thomas & Schechter used column flow; magnetic supports were a standard alternative enumerated in the specification itself.
- Claims 3–4 (release with dilute alkali, e.g., 0.5 M NaOH): recovery of the captured nucleic acid is the express purpose of both Thomas & Schechter (salt-gradient elution) and Vacek (1 M NaCl elution). Substituting NaOH — a standard denaturant that disrupts intercalation — is an obvious alternative with a predictable result, satisfying KSR's "known technique to improve a known device" rationale. (One nuance: the applicants' own data show 77–100% release with 0.5 M NaOH versus Vacek's concern about "irreversible binding" — a modest unexpected-results argument, but a weak one because alkali elution of nucleic acids was commonplace.)
- Claims 5–6 (beaded support: sepharose, agarose, magnetic beads): agarose/Sepharose beads are literally the supports of Chirikjian and Thomas; polyacrylamide beads are Vacek's support; magnetic beads are a conventional variant.
- Claims 7–8 (polymeric support as tube, dipstick, or microtiter plate): conventional assay formats; Chu/immobilization art and the specification's own disclosure make these routine design choices.
- Claims 9–10 (membrane; nylon): nylon and nitrocellulose membranes for nucleic-acid capture/blotting were standard well before 1987 (the specification concedes "[i]t is known that DNA adheres to nitrocellulose," and the examples use Biodyne nylon). Obvious.
7. Counterarguments a patent owner would raise (and why they are weak here)
- "No reference suggests methidium-on-support for unpurified samples." True but not dispositive — KSR holds an explicit teaching, suggestion, or motivation is not required. The suggestion comes from the problem, the art's direction of improvement, and the known properties of the elements.
- "Thomas & Schechter and Vacek teach away." Partially true as to ethidium-based supports, but a teaching away must be clear enough to discourage the claimed approach. Here the same references supply the elution/salt-manipulation framework that points toward tuning the intercalator and linker for greater affinity — i.e., toward, not away from, the invention.
- "Unexpected results (Table I)." The strongest argument; but unexpected-results evidence must be commensurate with the claim scope and must be shown to be unexpected in kind or mechanism (In re Soni; In re Geisler-type requirements). Because the specification itself attributes salt tolerance to the cationic polyamine linker, and Dervan & Becker taught the large affinity gain, the results are arguably predictable in character.
- "Long-felt need and commercial success." The need is documented, but it is the same need that motivates the combination, and any commercial success would need a nexus to the specific methidium–spermine structure rather than to the generic capture concept.
8. Confidence and caveats
- Confidence that claims 2–10 are obvious: high.
- Confidence that claim 1 is obvious: moderate — the combination is well-supported, but the salt-independence limitation and the applicant's comparative data make this a defensible case on both sides. My estimate is a modest tilt (≈60–65%) toward invalidity.
- Retrospective-analysis caveat: this opinion reasons from the references the examiner actually cited and from the level of skill in 1987; it necessarily risks hindsight. The examiner allowed the case, meaning the salt-independence limitation was accepted as distinguishing over Thomas & Schechter/Vacek at the time.
- Adjacent issue not analyzed here: the functional "independent of the salt concentration" language also raises a potential § 112 written-description/enablement question, which I flag only as adjacent and do not resolve.
- Consistency note (not a contradiction): the prior sections flagged the claim 1(b) word "insulating" (and claim 10's "claim reagent of claim 9") as apparent OCR artifacts. Two independent renderings reviewed here — Google Patents and FreePatentsOnline — both show "insulating," so the artifact may originate in the printed patent or a shared scan rather than in one OCR pass. I continue to treat these as typographical artifacts, not substantive claim limitations.
Sources relied on: https://patents.google.com/patent/US4921805/en; https://www.freepatentsonline.com/4921805.html; Thomas & Schechter, Anal. Biochem. 91:209–23 (1978) (https://pubmed.ncbi.nlm.nih.gov/[9762101](/patent/9762101)/); Vacek et al., Anal. Biochem. 124:414–20 (1982) (https://pubmed.ncbi.nlm.nih.gov/[7149239](/patent/7149239)/); Chirikjian, US 4,119,521 (https://patents.google.com/patent/[US4119521A](/patent/US4119521A)/en); Dervan & Becker, JACS 100:1968–70 (1978); Dervan, US 4,665,184.
Generated 9/27/2026, 8:03:48 PM
Extensions
Patent term adjustments, term extensions, continuations, divisionals, family members, and expiration dates.
Derivative works
Defensive disclosure: derivative variations of each claim designed to render future incremental improvements obvious or non-novel.
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