Invalidity dossier

US 5252743

Spatially-addressable immobilization of anti-ligands on surfaces

Current assignee: Affymetrix Inc

Added 9/27/2026, 6:24:31 PM

At a glanceNo PTAB challengesNo litigation on fileBiotechnology

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Patent summary

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

✓ Generated

I'll verify against live sources, then summarize.

Let me try to retrieve the actual claim text.

US Patent 5,252,743 — Analyst Summary

Scope note: I could not query PACER, the CAFC docket system, or USPTO PatentCenter/PTAB APIs directly — only open-web search. Results below are grounded in the full patent text supplied to me (Google Patents, fetched 2026-09-27, https://patents.google.com/patent/[US5252743](/patent/US5252743)/en) plus corroborating public copies. Gaps and uncertainties are flagged at the end.


1. Bibliographic data (as listed)

Field Value
Patent number US 5,252,743 A
Title Spatially-addressable immobilization of anti-ligands on surfaces
Inventors Ronald W. Barrett (Sunnyvale, CA); Michael C. Pirrung (Durham, NC); Lubert Stryer (Stanford, CA); Christopher P. Holmes (Sunnyvale, CA); Steven A. Sundberg (San Francisco, CA)
Original assignee Affymax Technologies N.V. (Netherlands Antilles corp.)
Current assignee (as listed) Affymetrix Inc.
Application no. 07/612,671
Filing date 1990-11-13
Priority date 1989-11-13 (CIP of 07/435,316, filed 1989-11-13, now abandoned)
Issue date 1993-10-12
Status Expired – Lifetime (anticipated expiration 2010-10-12)
Primary classification C07D 495/04; also C07D 491/048, C07D 235/02; G01N 33/543, G01N 33/552; C40B 40/06
Examiners / counsel Joseph Paul Brust (primary); Mary Susan H. Gabilan (asst.). Kaster, Weaver & Dow

Assignment chain: Affymax Technologies N.V. → Affymetrix, Inc. (recorded 1998-02-12); merger assignment re Affymetrix, Inc. (CA corp. → DE corp.), 1998-12-23; security agreement to General Electric Capital Corporation as agent, 2012-06-27; release by secured party, 2015-11-13.


2. Abstract (verbatim)

"Methods and compositions are described for immobilizing anti-ligands, such as antibodies or antigens, hormones or hormone receptors, oligonucleotides, and polysaccharides on surfaces of solid substrates for various uses. The methods provide surfaces covered with caged binding members which comprise protecting groups capable of being removed upon application of a suitable energy source. Spatially addressed irradiation of predefined regions on the surface permits immobilization of anti-ligands at the activated regions on the surface. Cycles of irradiation on different regions of the surface and immobilization of different anti-ligands allows formation of an immobilized matrix of anti-ligands at defined sites on the surface. The immobilized matrix of anti-ligands permits simultaneous screenings of a liquid sample for ligands having high affinities for certain anti-ligands of the matrix. A preferred embodiment of the invention involves attaching photoactivatable biotin derivatives to a surface. Photolytic activation of the biotin derivatives forms biotin analogs having strong binding affinity for avidin. Biotinylated anti-ligands can be immobilized on activated regions of the surface previously treated with avidin."


3. Plain-language overview

The patent is an early Affymax/Affymetrix "array" patent. The problem it addresses: how to attach many different biological capture molecules (antibodies, receptors, oligonucleotides) at different, precisely known spots on one solid surface.

The mechanism:

  1. A "caged" binding member — a small binding molecule chemically blocked with a photolabile protecting group (prototype: N‑1'‑nitroveratryloxycarbonyl‑biotin, "NVOC‑biotin") — is attached to the surface, optionally through a crosslinker/linker (e.g., N‑BOC‑aminopropyltriethoxy silane plus 6‑aminocaproic acid spacers).
  2. Because the cage blocks its binding site, the caged molecule has very low affinity for its partner. The specification states the activated form's affinity constant should be at least ~3 orders of magnitude higher (preferably ~5–7 orders of magnitude higher) than the caged form's.
  3. Spatially addressed irradiation through a photolithographic mask removes the cage only in predefined regions ("predefined region S_i"), restoring the real binding member (biotin) there.
  4. Avidin/streptavidin is bound to the activated regions, and a biotinylated anti-ligand (e.g., biotinylated antibody) is then immobilized via the multivalent biotin–avidin bridge. Alternatively, a pre-formed avidin/biotinylated-anti-ligand conjugate is presented to the surface.
  5. Repeating the irradiate-then-immobilize cycle at other regions yields a matrix of different anti-ligands at defined coordinates, usable for simultaneous screening/assaying of labeled ligands (autoradiography, fluorescence).

The specification also lists non-photochemical activation modes (electron-beam, X-ray, ion-beam lithography, electric current via microelectrodes) and non-biotin embodiments (cAMP/anti-cAMP antibodies, NVOC-tetrahydrofolate/folate binding protein, 6-(nitroveratryloxy)mannoside/concanavalin A). The 1995 JACS paper (Sundberg et al., J. Am. Chem. Soc. 117:12050) reports the reduction to practice (~500 µm × 500 µm streptavidin spots; two biotinylated antibodies at different sites).

Important structural point: despite the method-oriented title and abstract, the '743 patent's claims are all chemical compound claims — 15 claims, one independent. The method claims ("immobilizing anti-ligands on predefined regions…") appear in the two divisional patents, US 5,482,867 and US 5,453,683 (both filed 1993-04-23 from 07/612,671). I have not verified the divisional claim text and will not paraphrase it.


4. Independent claim (claim 1) — plain language

There is one independent claim; claims 2–15 all depend (2–8 on claim 1; 9–11 on claim 8; 12–15 on claim 1).

Claim 1 — "A caged binding member compound having the formula: [structure STR30]"

Plain-language reading: a photolabile-protected biotin/biotin-analog molecule — i.e., the reagent, not a method — defined by a genus with these variable parts:

  • X and Z are hydrogen or oxycarbonyls of lower alkyl, aryl, and benzyl groups, with a proviso that eliminates (a) underivatized biotin (X=Z=H) and (b) the mono-methyloxycarbonyl species. In other words, at least one ring nitrogen must carry a genuine protecting group, and methyl carbamate alone does not count.
  • R is the substituent at the carboxyl terminus: hydrogen, lower alkyl, aryl, lower alkyl formate, aryl formate, formamide, N-alkylformamide, N-succinimidyl, hydroxyl, alkoxyl, thiol, thioether, disulfide, hydrazide, or amine — provided that when X or Z is methyloxycarbonyl, R is not methyl formate.
  • U is O, S, or NH (the heteroatom of the fused ring).
  • Y is sulfur, oxygen, methylene, carbonyl, sulfinyl, or sulfonyl, or Y is two hydrogens on the respective carbons (i.e., the sulfur-containing ring is absent, leaving the open-chain/imidazolidinone form).
  • n = 1–7 (length of the carboxy-side chain).
  • Also covered: acid addition salts of the compound.

R covers both a free/activated carboxyl (usable for coupling to a surface) and ester/amide/activated-ester forms. In effect, claim 1 monopolizes the class of caged biotin reagents whose blocking groups sit on the ureido-ring nitrogens so that avidin/streptavidin binding is suppressed until light removes them.

Dependent claims (short form)

Claim Depends on Adds
2 1 U = O, Y = S, n = 4 (natural biotin ring system)
3 1 One of X, Z is a nitroveratryloxycarbonyl group
4 1 One of X, Z is an oxycarbonyl with an o-nitrobenzyl-type ring bearing R1/R2 (H, alkyl, aryl, benzyl, halogen, OH, alkoxyl, thiol, thioether, amino, nitro, carboxyl, formate, formamido, phosphido)
5 1 X = 6-nitroveratryloxycarbonyl, Z = H, R = methyl formate (NVOC-biotin methyl ester)
6 1 X = NVOC, Z = H, R = p-nitrophenyl formate (NVOC-biotin-ONP)
7 1 X = 6-nitropiperonyloxycarbonyl (NPOC), Z = H, R = p-nitrophenyl formate
8 1 One of X, Z is a ring-disubstituted benzyloxycarbonyl
9 8 Recites a further generic formula with R1, R2, R3, R4 (this claim reads as grammatically defective — the text supplied ends "…benzyloxycarbonyl group." immediately before the formula)
10 9 R1 and R2 are methoxy
11 9 R3 and R4 are methyl
12–15 1 Four specifically named compounds whose structures appear only as chemical drawings (STR33–STR36)

Note on claims 12–15: I cannot state their identity with confidence, because the patent reproduces them as structures rather than names and my sources render the structure blocks as image placeholders. The specification's Examples separately describe DDZ‑biotin‑OMe and PYROC‑biotin‑OMe, so it is plausible (but unverified) that some of 12–15 correspond to those or to the MeNVOC/MeNPOC analogues later published by the same inventors. Treat claims 12–15 as unidentified without image access to the printed patent.


5. Priority family (for context, not part of the summary request)

  • 07/435,316 (filed 1989-11-13) — parent, abandoned; '743 is a CIP of it.
  • US 5,252,743 — 07/612,671, filed 1990-11-13.
  • US 5,482,867 — 08/054,121, filed 1993-04-23, stated divisional; 16 claims.
  • US 5,453,683 — 08/053,124, filed 1993-04-23, stated divisional.
  • PCT publication WO 91/07807 is cited in later literature as the counterpart publication.

6. Litigation / CAFC 2026 docket — negative finding

I found no evidence of any 2026 CAFC docket activity involving US 5,252,743. Targeted searches for the patent number against Federal Circuit case lists, PTAB/IPR institution and discretionary-denial roundups, and 2026 Federal Circuit decision summaries returned nothing referencing 5,252,743. No IPR/PGR, reissue, or reexamination proceeding for this number surfaced either.

Two reasons this negative result is unsurprising:

  1. The patent expired 2010-10-12 (17 years from the 1993-10-12 issue date; also 20 years from the 1990-11-13 filing date — both land on the same date), so it has been unenforceable for over 15 years.
  2. It issued in the pre-URAA era, and its asserted-era relevance (Affymetrix array/biochip litigation) predates 2026 by decades.

Caveat: This is a negative finding from open-web sources, not an authoritative docket check. I could not run a PACER or CAFC CM/ECF query, so I cannot exclude a recently filed or sealed matter. If an authoritative docket confirmation is needed, it should be run directly against PACER and the CAFC docket.


7. Explicit uncertainties

  1. Claims 12–15 identify compounds by drawing only; I could not resolve their structures (see §4).
  2. Claim 9 as published reads as grammatically incomplete; I have reproduced the defect rather than repair it. I cannot confirm whether this is a printing artifact or the literal granted text.
  3. Related-numbers inconsistency in the family (reported literally, not corrected): the specification of US 5,482,867 refers to the parent as "Ser. No. 07/612,571 … now U.S. Pat. No. 5,252,743," and elsewhere within the same patent text to "U.S. Pat. No. 5,252,473," and to a 1989 parent as "filed Nov. 13, 1988." The authoritative bibliographic data for the '743 patent itself is application 07/612,671, filed 1990-11-13, parent filed 1989-11-13. The '867 specification's numbers and date appear to be typographical discrepancies in that document; I flag them rather than silently reconciling them.
  4. Claims 1–15 are compound claims. If you need the method claims (spatially addressed immobilization), they belong to US 5,482,867 / US 5,453,683, and I have not verified their text.
  5. Bibliographic fields (assignee, status, expiration) are as listed by Google Patents, which itself disclaims legal-effect accuracy; assignment records should be confirmed at USPTO Assignment for anything load-bearing.

Sources: https://patents.google.com/patent/US5252743/en (authoritative full text, supplied); claims text corroborated at https://FreePatentsOnline.com/5252743.html and https://be.espacenet.com/publicationDetails/claims?CC=US&NR=[5252743A](/patent/5252743A) ; family data from https://patentimages.storage.googleapis.com/19/9f/02/e37b972c843520/US5482867.pdf.

Generated 9/27/2026, 7:02:42 PM

Cases on file (0)

Specific litigation cases in our database that name US patent 5252743. 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.

✓ Generated

I'll research litigation involving US Patent 5,252,743. Let me run several targeted searches.

Let me search more specifically for litigation databases and Affymetrix-related suits.

Bottom line

Based on my searches, I found no litigation — past or pending — in which US Patent 5,252,743 was asserted, challenged, or otherwise named as a patent-in-suit. I could not identify any case with a plaintiff, defendant, jurisdiction, and case number that involves the '743 patent specifically. It appears the '743 patent was never litigated (or at least no public record of litigation surfaced), and its term has now run: per the Google Patents record, the patent was granted 1993‑10‑12 with an anticipated expiration of 2010‑10‑12, so it is long expired and unenforceable. That alone makes modern assertion impossible and makes older litigation (if any) the only possible source.

I want to be explicit about confidence: this is a negative finding based on the searches I was able to run, not a certification that no case exists. I could not directly query PACER or the Unified Patents litigation portal (portal.unifiedpatents.com/litigation/caselist) — those returned no usable direct results through my search tool — so my conclusion rests on Google Patents, Justia, CourtListener/RECAP snippets, SEC filings, and secondary press.

What I searched and where

  • Google Patents entry for US5252743A — https://patents.google.com/patent/[US5252743](/patent/US5252743)/en (bibliographic/assignment/status data)
  • Keyword searches pairing "5252743" / "5,252,743" with litigation, infringement, complaint, plaintiff, defendant
  • Affymetrix/Affymax portfolio litigation searches (Affymetrix v. Illumina, Oxford Gene Technology v. Affymetrix, Enzo/Yale cases)
  • CourtListener/Justia snippets and SEC filings (Illumina 10‑K, Enzo annual report)

Near-misses found — and why they are not US 5,252,743

These are the results that a less careful search would wrongly report as "'743 litigation." I'm flagging each so the record is clean:

  1. Axsome Therapeutics v. Alkem Laboratories (D.N.J., 2025–2026) — Count I is captioned "Infringement of the '743 Patent" and pleads infringement under 35 U.S.C. § 271(e)(2)(A). This is an ANDA/pharmaceutical case and the '743 patent there is a drug patent, not US 5,252,743 (a 1993 surface-immobilization patent). Different patent, same trailing digits.
  2. Affymetrix, Inc. v. Illumina, Inc. (D. Del., the "BeadArray" litigation) — Filed against Illumina, with a jury verdict of infringement in March 2007 and $16.7M in damages; also a second wave of US/UK/German suits in October 2007. A Duke University report on the case refers to one patent-in-suit as the "'243 patent," but the technology it describes ("assessing nucleic acid binding to a substrate with at least 1000 different spheres, beads, or particles") does not match US 5,252,743's disclosure or claims (caged binding members / photolabile biotin on surfaces). I therefore cannot treat that reference as evidence that US 5,252,743 was asserted, and the secondary source is ambiguous. Sources: Illumina 10‑K excerpt (stocklight.com copy); Duke Space case study; Foley Hoag reprint in Drug Discovery News, Nov. 2007.
  3. Oxford Gene Technology Ltd. v. Affymetrix, Inc. (D. Del., jury verdict Nov. 2000) — Unrelated OGT patent (the "Southern patents"); not '743.
  4. Enzo Life Sciences/Yale University v. Applera/Tropix (D. Conn.) — Ward patents; not '743.
  5. Reexamination materials referring to "US 7,400,274" or "'274 patent" — a different patent (CME Group reexamination); not '743.
  6. CourtListener and Florida Sunbiz "5252743" hits — these are an unrelated investment-record ID and a Florida LLC's FEI employer number, not the patent.
  7. Justia patent pages (e.g., US 7,659,063; US 6,486,286; US 12,139,745) that display "5252743 | October 12, 1993 | Barrett et al." — these are just front-page prior-art/reference citations to the '743 patent, not litigation.

Related context that could be useful

  • The '743 patent is part of the Affymax/Affymetrix "VLSIPS" family. Google Patents records its original assignee as Affymax Technologies N.V., later assigned to Affymetrix, Inc. (1998), with a merger to Affymetrix Inc. (a Delaware corp.) later in 1998. Its siblings sharing the same disclosure include US 5,451,683 and US 5,482,867 (both claiming priority from the same application), and the family is cited throughout later Affymetrix patents (e.g., US 6,486,286; EP 1,345,026; EP 2,497,837).
  • The patent appears in the prior-art/background discussion of many later patents and opposition/reexamination documents (e.g., JP 2003‑060037 cites WO 91/07087 as the family's PCT publication, corresponding to US 5,252,743; EP 1,664,343 B1 cites it at [0093]). Those are citations, not assertions.

Limitations of this answer

  • I could not access PACER, Docket Navigator, Lex Machina, or the Unified Patents litigation caselist directly; my tool returned only general search results for those.
  • Free sources index patent-infringement complaints unevenly, particularly for pre‑2000 cases, and complaints sometimes list patents only in exhibits. A suit filed in the 1990s that was voluntarily dismissed, or resolved before appeal, could be missing from the sources I checked.
  • District court complaints and dockets for older Affymetrix cases are not fully text-searchable in the results I saw; I also did not find any PTAB/IPR, ITC Section 337, or reexamination proceeding naming US 5,252,743.

Suggested verification steps if you need a diligence-grade answer: run a patent-number search in Docket Navigator or Lex Machina (both index by patent number), pull the full docket sheets for the Delaware Affymetrix cases (e.g., the 2004 Illumina case, D. Del. Civ. No. 1:04‑cv‑00901, and the 2007 follow-on), check the USPTO Patent Center "litigation/assignment" records for US 5,252,743, and search the Westlaw KeyCite patent history line for the patent. If any of those returns a case naming US 5,252,743, I'd want to see the complaint itself rather than a secondary reference in which the number appears only as "the '243 patent."

Generated 9/27/2026, 7:02:42 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.

✓ Generated

I'll verify the canonical "no PTAB activity" signal against web search before reporting.

Let me run a couple more targeted checks before concluding, including for any reexamination/litigation history.

Proceedings overview

Zero AIA trial proceedings on file. The canonical structured block ("PTAB proceedings on file") reports that the USPTO ODP API returns no AIA trial proceedings for US 5,252,743 as of the most recent ingest — no IPR, no PGR, no CBM — and independent web searching surfaced nothing contradicting that. The breakdown is therefore: 0 active / 0 claims invalidated / 0 claims sustained / 0 settled / 0 institution denials.

The bottom line for a defendant is unusual and blunt: there is no PTAB record at all — not because the patent is "hardened" by surviving challenges, but because the patent is expired. Per the Google Patents file, the term ran out on 2010-10-12 ("Anticipated expiration," legal status Expired - Lifetime), and IPR/PGR/CBM did not exist until the AIA trial provisions took effect on 2012-09-16. There is no IPR estoppel record to mine, no FWD to cite, and — critically — no live damages theory for new conduct. If a demand letter cites US 5,252,743 today, the operative defense is not an IPR at all; it is expiry plus the § 286 six-year damages bar.

⚠️ Search false-positive alert: web searches for "the '743 patent" are dominated by different patents — US 9,840,743 (Foundation Medicine v. Guardant Health, IPR2019-00634), US 10,687,745 and related Apple v. Masimo pulse-oximetry IPRs (IPR2022-01241, IPR2022-01242, IPR2022-01291, IPR2022-01465), and InfoGation Corp.'s software '743 patent. None of these involve US 5,252,743. Do not let a demand letter or a research memo conflate them.

Proceedings

None. There is no proceeding number, petitioner, panel, institution decision, final written decision, settlement, or appeal to report for US 5,252,743. Per the operating constraints, I will not invent one.

Strategic summary

Claim status: entire patent expired, no claim ever adjudicated by the PTAB. No claim of US 5,252,743 is CANCELED by the Board, none is SUSTAINED by the Board, and all claims are UNTESTED in AIA trials. The relevant status is not claim-by-claim but patent-level: the patent issued 1993-10-12 from application 07/612,671 (filed 1990-11-13, priority 1989-11-13, a CIP of abandoned Ser. No. 07/435,316) and expired 2010-10-12 on the pre-URAA 17-years-from-grant measure, which the Google Patents transaction history records as "Anticipated expiration." Enforcement of expired claims is limited to past damages, and § 286 bars recovery for infringement occurring more than six years before a complaint is filed — so any actionable damages window closed long ago. The patent had a family in the same subject matter (US 5,451,683 and US 5,482,867, both accorded 1993-04-23 priority from the same disclosure per the Google Patents "Priority to" entries); if you are dealing with an asserted portfolio rather than a single patent, those are the ones worth a separate expiry check.

Estoppel landscape: none exists. There is no FWD on this patent, so § 315(e)(2) estoppel never attached to anyone, and no petitioner is foreclosed from any ground. Conversely, a defendant has no PTAB win to leverage. Because the patent is expired, an IPR would be a poor use of resources: the Board does institute on expired patents (claims cannot be amended, and the Board applies Phillips rather than the broadest reasonable interpretation), but the practical reward is a validity ruling on claims that can no longer be infringed prospectively. Notably, the Family's expired-patent reexamination rulings discussed in the literature (see the Patents Post-Grant discussion of expired-claim construction) illustrate the narrow posture such challenges occupy — they are about preserving past-damages defenses, not about prospective freedom to operate.

Pattern signals: not applicable, and one substantive caution. There is no repeat petitioner, no defensive aggregator (no Unified Patents challenge appears in the record — the Unified Patents page for US-5252743-A is a citation/landscape page, not a challenge), and no PTAB appeal history. Separately, the patent owner's litigation history is real but does not include this patent: Affymetrix's Delaware suit against Illumina (filed 2004-07-26) asserted six Affymetrix patents, and the 2007 reexamination requests and the $90 million January 2008 settlement concerned US 6,355,432, 6,646,243, 5,545,531, and 5,795,716 — not US 5,252,743 (see the Illumina settlement report and Patent Docs). Interference No. 104,552 (Affymetrix/Hyseq) likewise involved US 5,795,716, not this patent. Do not attribute that litigation history to US 5,252,743.

Recommended next steps

  1. Say it plainly: no PTAB activity exists on US 5,252,743. The absence here is not the usual "well-asserted patents eventually attract IPRs" signal, because the patent expired 2010-10-12, roughly two years before AIA trials became available on 2012-09-16. Confirm independently via the USPTO Patent Trial and Appeal Board E2E and the Google Patents file for US5252743A.
  2. If you are a defendant facing an assertion, do not build an IPR budget. Build an expiry file: the 2010-10-12 expiration date, the § 286 six-year damages limitation, and the absence of any post-expiration infringement theory. Request the plaintiff's damages model and demand it identify infringement within a window that can still be recovered.
  3. If a demand letter cites "the '743 patent," verify the number character-by-character. The high frequency of unrelated '743 patents (9,840,743; 10,687,745; InfoGation's) makes citation error a realistic threat — and if the letter cites US 5,252,743 and any of the '743 litigation or IPR history just described, the sender has misidentified the patent.
  4. If the assertion is framed around the Affymetrix microarray family rather than this patent, the operative patents are US 5,451,683 and US 5,482,867 (same 1993-04-23 priority lineage per Google Patents) — those warrant their own PTAB and expiry checks, which I have not performed here.

Confidence note: I have high confidence in "no AIA proceedings on this patent" based on the structured ODP block plus three independent search passes. I have high confidence in the 2010-10-12 expiration date (stated verbatim in the Google Patents transaction history). I do not have evidence of any ex parte reexamination of US 5,252,743 specifically, and I am not asserting that none occurred — the reexaminations I found in the record attach to other Affymetrix patents.

Generated 9/27/2026, 7:02:38 PM

Ownership chain (5)

Asserters network →

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

  1. ? · recorded 1991-01-11 · Assignment

    Ronald W. Barrett; Lubert Stryer; Michael C. Pirrung; Christopher P. Holmes; Steven A. SundburgAFFYMAX TECHNOLOGIES N.V.

    inventor vesting

  2. ? · recorded 1998-02-12 · Assignment

    AFFYMAX TECHNOLOGIES N.V.Affymetrix, Inc.

    internal reorg

  3. ? · recorded 1998-12-23 · Merger

    Affymetrix, Inc., a corp. of CaliforniaAffymetrix Inc., a corp. of Delaware

    internal reorg

  4. 2012-06-25 · recorded 2012-06-27 · Security Agreement

    Affymetrix, Inc.General Electric Capital Corporation, as Agent

    securitization

  5. ? · recorded 2015-11-13 · Release

    General Electric Capital Corporation, as AgentAffymetrix, Inc.

    lien release

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 start by pulling the assignment/legal-event records from multiple sources to try to recover reel/frame and correspondent data.

Good — I'm getting useful signal. Let me dig for the specific reel/frame numbers and any post-2010 transfers (Thermo Fisher, Life Technologies).

Ownership & Assignment Reconstruction — US 5,252,743

Sourcing note up front (read before the timeline). The authoritative patent text supplied for this analysis contains Google Patents' legal-events table for US 5,252,743, which gives dates, conveyance types and party names but does not expose reel/frame numbers or correspondent-of-record names. In this session I was able to reach Google Patents legal events, Espacenet INPADOC legal data, FreePatentsOnline, Justia and Unified Patents, but I was not able to open the USPTO Assignment Center record itself or any mirror that renders the reel/frame for this patent (plainsite.org assignment pages surfaced only for unrelated Affymax patents). Where I cite a reel/frame below I say explicitly whether it is confirmed for '743 or merely the parallel instrument on a sibling Affymetrix patent. I have not invented any reel/frame or attorney name. Two spurious search hits are noted at the end so they don't contaminate the file.


Inventors

Five named inventors (front page and the 1991-01-11 recordation):

Inventor Employer/affiliation at filing (determinable)
Ronald W. Barrett Affymax (Palo Alto, CA) — company scientist
Michael C. Pirrung Stanford University — Assistant Professor of Chemistry (academic collaborator, not an Affymax employee at filing). Later Duke University; in the 1998 N.D. Cal. venue opinion he is described as "a professor at Duke University and resides in North Carolina."
Lubert Stryer Stanford University — Winzler Professor, School of Medicine / Neurobiology; also on Affymetrix's Scientific Advisory Board
Christopher P. Holmes Affymax — company scientist (later inventor on Affymetrix-assigned patents such as US 5,242,974 and US 5,527,681)
Steven A. Sundberg Affymax — company scientist (later inventor on US 5,624,711, "Derivatization of solid supports…", assigned to Affymax Technologies N.V.)

Unusual patterns: none of the classic fire-sale tells. Three inventors were operating-company employees and two were Stanford academics whose relationship to the assignee was collaborative rather than employment — so the "all inventors leave the assignee within 12 months" heuristic is meaningless here. The inventors were named as assignors of record in the 1991-01-11 instrument (see below), which is the normal route to vesting in Affymax Technologies N.V.

Spelling discrepancy to note on the record: the printed patent lists "Steven A. Sundberg"; the recorded 1991-01-11 assignment instrument (as transcribed by Google Patents) spells the assignor "SUNDBURG, STEVEN A." Treat the recorded instrument's spelling as authoritative for that document (per the instruction to interpret identifiers literally), but flag the variance if you are reconciling parties.


Original assignee

Affymax Technologies N.V. — a Netherlands Antilles corporation. This is the assignee named in the front-page (bib) data and current-assignee field of Google Patents.

  • Business: Affymax was a Palo Alto drug-discovery company founded by Alejandro Zaffaroni, using combinatorial/peptide-library technology. The microarray work that produced this patent was conducted inside Affymax; Affymetrix was incorporated in 1992 as a California corporation and a wholly-owned subsidiary of Affymax, and spun the GeneChip technology out. The Netherlands Antilles N.V. was the group's IP-holding vehicle for the Affymax research estate — note this is a pre-existing corporate structure of a 1980s–90s venture-backed company, not a post-hoc NPE vehicle.
  • Did they ship a product embodying the claims? Affymax itself did not commercialize this patent. The claims (1–15) cover caged/photoactivatable biotin derivatives — i.e., the photolabile-protecting-group chemistry underpinning light-directed, spatially addressable array synthesis. The commercial embodiment is the Affymetrix GeneChip platform, which Affymetrix began selling in 1996 and which became a large, real product line (case study: Nature Biotechnology nbt.2033 — Affymetrix >1,000 employees, ~$311M revenue by that year). So: the technology shipped, but by the corporate successor, not the named assignee.
  • Current status: Affymax (the parent) was acquired by Glaxo in March 1995 for ~US$500M, which included Affymax's then-65% stake in Affymetrix. The N.V. IP-holding entity was not a going concern thereafter; its microarray patents were swept to Affymetrix, Inc. in 1998 (below). Affymetrix, Inc. itself was acquired by Thermo Fisher Scientific (announced Jan 2016, completed 2016), and reorganized into Thermo Fisher's genetic-analysis business. Neither the original assignee nor its successor is in bankruptcy.

Assignment timeline

Google Patents legal events for US 5,252,743 (the only party/date record I could retrieve directly for this patent). Reel/frame is marked confirmed only where I have a source rendering it against '743 — it is not exposed in the sources I could reach for '743, so reel/frame strings below are the parallel instrument on sibling estate patents and are labelled as such.

  • 1990-11-13 / recorded 1990-11-13 — Reel/frame not retrieved for '743

    • Conveyance: Application filed (CIP of Ser. No. 07/435,316, filed 1989-11-13, now abandoned)
    • Assignor: n/a
    • Assignee: Affymax Technologies NV (applicant of record)
    • Correspondent: not retrievable
    • Context: initial filing — the 1989-11-13 priority is the family's anchor date for all cited art and for patent-term/status purposes.
  • 1991-01-11 (recorded) / execution date not stated — Reel/frame not retrieved for '743

    • Conveyance: Assignment of assignors' interest (inventor → company)
    • Assignor: Ronald W. Barrett; Lubert Stryer; Michael C. Pirrung; Christopher P. Holmes; Steven A. Sundburg (as spelled in the record)
    • Assignee: AFFYMAX TECHNOLOGIES, N.V., a Netherlands Antilles corp.
    • Correspondent: not retrievable
    • Context: founder/inventor vesting — standard startup IP assignment; not an ownership change of economic substance.
  • 1993-10-12 — Patent granted (US 5,252,743 B1)

    • Two continuation applications filed 1993-04-23 also claim priority to this family (Ser. 08/054,121 → US 5,482,867; Ser. 08/053,124 → US 5,451,683). These are family relationships, not assignments; I include them so they are not mistaken for chain links.
  • 1998-02-12 (recorded); effective 1997-02-22 (per the parallel instrument) — Reel/frame not retrieved for '743; the parallel Affymax→Affymetrix recording on sibling patent US 5,510,270 carries Reel 008955/0530 (Espacenet INPADOC). A second recording on the same day bears Reel 009543/0953 on a different Affymetrix patent (US 6,308,170, there for an inventor-assignment from Balaban). Treat 008955/0530 as indicative, not confirmed for '743.

    • Conveyance: Assignment of assignors' interest ("see document for details")
    • Assignor: Affymax Technologies N.V.
    • Assignee: Affymetrix, Inc. (California)
    • Correspondent: not retrievable
    • Context: internal portfolio migration / spin-out cleanup — the microarray estate was moved from the old Affymax N.V. holding company to the separately listed Affymetrix entity after Affymetrix's June 1996 IPO and after Glaxo (now Glaxo Wellcome) had absorbed the Affymax parent. Not a fire-sale: this is a strategic de-coupling of the chip IP from the drug-discovery parent.
  • 1998-12-23 (recorded) — Reel/frame not retrieved

    • Conveyance: Merger ("see document for details")
    • Assignor: Affymetrix, Inc., a corp. of California
    • Assignee: Affymetrix Inc., a corp. of Delaware
    • Correspondent: not retrievable
    • Context: reincorporation / change of domicile only (shareholders voted June 1998; completed Sept 1998 per the N.D. Cal. opinion in the Hyseq litigation). No change in economic ownership; no change in business.
  • 2012-06-27 (recorded); executed 2012-06-25 — Reel/frame not retrieved for '743; the identical instrument on sibling patents US 6,308,170 and US 6,410,229 carries Reel 028465/0541 (Espacenet INPADOC). Indicative, not confirmed for '743.

    • Conveyance: Security Agreement (grant of security interest)
    • Assignor: Affymetrix, Inc.
    • Assignee: General Electric Capital Corporation, as Agent
    • Correspondent: not retrievable
    • Context: securitization / collateral — blanket IP lien supporting the US$100,000,000 Credit Agreement dated 2012-06-25 among Affymetrix (borrower), GE Capital (agent) and the lenders, filed as an 8-K exhibit (SEC accession 0001193125-12-282333). Not a transfer of ownership. Note this lien was recorded against a patent that had already expired (2010-10-12, anticipated expiration) — routine portfolio-wide lien practice, not evidence of value in '743.
  • 2015-11-13 (recorded) — Reel/frame not retrieved for '743; identical instrument on sibling patents bears Reel 037109/0132 (Espacenet INPADOC). Indicative, not confirmed.

    • Conveyance: Release by Secured Party
    • Assignor: General Electric Capital Corporation, as Agent
    • Assignee: Affymetrix, Inc.
    • Correspondent: not retrievable
    • Context: lien release — GE Capital discharged its security interest, contemporaneous with the refinancing that brought in Bank of America, N.A. as Administrative Agent (security interest executed 2015-10-28, Reel 036988/0166 on sibling patents; released by Notice of Release recorded 2016-04-05, Reel 038361/0891). Again, these are blanket portfolio recordings.

No NPE, no shell LLC, no asserter, and no defensive aggregator appears anywhere in the recorded chain. There is no recorded assignment to Thermo Fisher Scientific or to Life Technologies Corporation for US 5,252,743 in the legal-events data I could retrieve; the record owner of record remains Affymetrix, Inc. (now a Thermo Fisher subsidiary as a matter of corporate fact, whether or not a merger assignment was recorded against this already-expired patent).

Data-integrity flags for the file:

  1. FreePatentsOnline's page for US 5,252,743 surfaces the string "LIFE TECHNOLOGIES CORPORATION (Carlsbad, CA, US)" near the header. Life Technologies (Carlsbad, CA) was itself acquired by Thermo Fisher in 2014, so a downstream Thermo Fisher-family recording is plausible, but I could not corroborate any such recordation against '743 and the placement suggests a page-scrape artifact. Do not treat this as a recorded assignment until a reel/frame is produced from Assignment Center.
  2. Searching the bare string "5252743" also returns a 2023 Florida LLC annual report for an unrelated entity ("URBAN DICE LLC," FEI 82-5252743). That is an EIN collision, not a patent record.

Timeline diagram

timeline
    title Ownership of US 5252743
    1989 : Priority application filed
    1990 : CIP filed by Affymax Technologies NV
    1991 : Inventors assign to Affymax Technologies NV
    1993 : Patent US 5252743 issues
         : Two continuation cases filed
    1995 : Glaxo acquires Affymax parent
    1996 : Affymetrix IPO
    1998 : Estate assigned to Affymetrix Inc
         : Affymetrix reincorporates in Delaware
    2010 : Patent term expires
    2012 : GE Capital records security agreement
    2015 : GE Capital lien released
         : Bank of America lien recorded
    2016 : Affymetrix acquired by Thermo Fisher

NPE / troll-pattern signals

  1. Shell-entity transfer — NOT PRESENT. Every recorded assignee is an operating entity: Affymax Technologies N.V. (drug-discovery parent), Affymetrix, Inc. (California, then Delaware — GeneChip manufacturer), and lienholders GE Capital / Bank of America. No "IP / Patents / Licensing / Holdings / Ventures" suffix, no registered-agent address, no single-member LLC appears in the chain (1991-01-11; 1998-02-12; 1998-12-23; 2012-06-27; 2015-11-13 records).

  2. Known asserter in the chain — NOT PRESENT. No Acacia, Marathon, Intellectual Ventures, IPNav, Wi-LAN, Mosaid/Conversant, Vringo, Pendrell, Innovatio, MPHJ, Lumen View, Round Rock, Document Generation, or Spangenberg entity appears on any recorded instrument. Affymetrix's own enforcement activity (Hyseq 1998; Incyte; Oxford Gene Technology; Illumina, with a 2007 jury verdict and 15% royalty finding) is operating-company assertion against actual competitors, not NPE conduct — and I found no evidence that US 5,252,743 itself was asserted in any of those suits.

  3. Repeat correspondent across the chain — UNCLEAR / NOT ASSESSABLE. The USPTO Assignment Center "correspondent of record" field is exactly the tell you asked for, but the sources I could reach do not render correspondent names for any of the '743 recordings (Google Patents legal events omit them; Espacenet INPADOC omits them; I could not open Assignment Center directly this session). On the record as I can see it, no correspondent recurs — but that is an absence of data, not a finding of absence. If you want this signal closed out, pull reel 008955/0530 and the 2012/2015/2016 instruments from Assignment Center and read the correspondent block: for 1990s Affymax/Affymetrix filings I would expect in-house counsel at the Santa Clara address, but I will not assert that without the document.

  4. Cascading transfers — NOT PRESENT. Only two substantive ownership transfers exist, eight years apart (1991 inventor vesting; 1998 Affymax N.V. → Affymetrix) plus a same-owner reincorporation (1998-12-23). Nothing resembling consecutive LLC-to-LLC hops inside 24 months, and no shared correspondent/address pattern is visible.

  5. Pre-litigation transfer — NOT PRESENT (for this patent). No assignment is dated within 6 months before an infringement suit naming US 5,252,743; no such suit was found. For completeness: the 1998-02-12 Affymetrix assignment preceded Affymetrix's 1998-08-18 complaint against Hyseq by about six months, but that complaint asserted the '305, '992 and '716 patents, not '743. Timing coincidence, not a standing-cleanup transfer for this patent.

  6. Bankruptcy fire-sale — NOT PRESENT. No Chapter 7/11. The two exits were going-concern acquisitions: Glaxo/Affymax at ~US$500M (March 1995) and Thermo Fisher/Affymetrix (2016). The 2012 GE Capital lien shows leverage, and it was released (2015-11-13), with no foreclosure or §363 sale. Affymetrix was never a Kodak/Nortel/Polaroid-style estate sale.

  7. Privateering — NOT PRESENT. No transfer to a third-party monetization vehicle, and no SEC or press evidence that an NPE asserted these claims on Affymetrix's behalf. Affymetrix litigated in its own name.

  8. Defensive aggregator — NOT PRESENT. The chain terminates at Affymetrix, Inc. / Thermo Fisher — an operating manufacturer. It does not terminate at RPX, AST, LOT Network, Unified Patents or OIN. (Unified's portal does index this patent as prior art in its database, which is prior-art indexing, not ownership.)


Verdict

Operating-company assertion.

The recorded chain is short and clean: inventors → Affymax Technologies N.V. (1991-01-11), then Affymetrix, Inc. (recorded 1998-02-12), a same-owner California→Delaware merger (1998-12-23), a GE Capital security agreement (2012-06-27) and its release (2015-11-13) — with no shell LLC, no listed asserter, no chained assignments, and no defensive aggregator anywhere in it. The ultimate owner, Affymetrix (now inside Thermo Fisher), is an operating microarray manufacturer that shipped the GeneChip products this chemistry underlies and litigated its microarray estate against genuine competitors (Hyseq, Incyte, Oxford Gene Technology, Illumina) — the inverse of an NPE profile. Two caveats stated plainly: (a) US 5,252,743 expired 2010-10-12, and I found no suit asserting this particular patent, so the "assertion" leg rests on the owner's corporate conduct rather than on a case naming '743; (b) the 2012 and 2015 lien recordings were portfolio-wide and swept in an already-expired patent, so they carry no signal about this patent's value. If strict proof of "was '743 ever asserted" is required, the honest answer is insufficient assertion data — but on ownership, the NPE hypothesis fails.

Verify at: https://assignmentcenter.uspto.gov/ (search patent number 5252743) — and cross-check https://patents.google.com/patent/US5252743/en for the legal-events dates cited above. To close out signal 3, request reel 008955/0530 and the 2012-06-27 / 2015-11-13 instruments and read the correspondent blocks.

Generated 9/27/2026, 7:03:23 PM

Prior art

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

✓ Generated

I'll start by verifying the patent record and locating its cited references.

I have the citation list. Now let me pull details on the most probative references.

Let me examine the remaining probative compound-disclosing references.

1. Patent identification (as verified)

Field Value
Patent number US 5,252,743 A
Title Spatially-addressable immobilization of anti-ligands on surfaces
Inventors Ronald W. Barrett; Michael C. Pirrung; Lubert Stryer; Christopher P. Holmes; Steven A. Sundberg
Original assignee Affymax Technologies N.V. (Netherlands Antilles); later assigned to Affymetrix, Inc.
Appl. No. / Filed 07/612,671, filed 1990‑11‑13
Priority 1989‑11‑13 (CIP of abandoned Ser. No. 07/435,316)
Granted / published 1993‑10‑12 (application published as WO 91/07087, 1991‑05‑30)
Status Expired – Lifetime (anticipated expiration 2010‑10‑12)
Sibling claim-bearing cases US 5,451,683 (from 08/053,124) and US 5,482,867 (from 08/054,121), each filed 1993‑04‑23

Verification note (important): the full text supplied to me (Google Patents scrape) was truncated before the front page "References Cited" block, so the citation list below was retrieved from the front-page facsimiles reproduced by FreePatentsOnline (FreePatentsOnline.com/5252743.html), EveryPatent (everypatent.com/comp/pat5252743.html) and SumoBrain, and cross-checked against the Espacenet claims record (be.espacenet.com/publicationDetails/claims?CC=US&NR=5252743A). I did not have direct USPTO PatentCenter image access in this session, so page-level verification of the citation block is by mirror, not by the Office record itself.


2. Threshold point that governs the entire § 102 analysis

All 15 granted claims of US 5,252,743 are compound claims. Claim 1 is a Markush compound claim to a "caged binding member" of the imidazolidinone/thieno-imidazolone type:

X and Z = H or oxycarbonyls of lower alkyl, aryl, benzyl (provided that when X is H, Z is not H or methyloxycarbonyl, and vice versa); R = H, lower alkyl, aryl, lower alkyl formate, aryl formate, formamide, N-alkylformamide, N-succinimidyl, hydroxyl, alkoxyl, thiol, thioether, disulfide, hydrazide, amine (provided that when X or Z is methyloxycarbonyl, R is not methyl formate); U = O, S or NH; Y = S, O, methylene, carbonyl, sulfinyl, sulfonyl, or two H's; n = 1–7; plus acid addition salts.

Claims 2–11 are narrowing compound claims (U=O/Y=S/n=4; nitroveratryloxycarbonyl; ring-disubstituted benzyloxycarbonyl; methoxy, methyl). Claims 12–15 recite specific structures (the NVOC-biotin-OMe / NVOC-biotin-ONP-type compounds actually made in Examples A–E).

Consequences:

  1. Every cited reference that is a method, apparatus, assay or surface-treatment disclosure is legally incapable of anticipating claims 1–15 under 35 U.S.C. § 102(a), (b), (e) or (g). It can only be background or § 103 (obviousness) material. Those references are marked "No § 102 reach" below.
  2. Anticipation of claim 1 could only come from a single reference disclosing a biotin/imidazolidinone ring bearing an alkoxy/aryloxy/benzyloxy-carbonyl on N‑1′ or N‑3′, with the remaining R/U/Y/n variables matching. Nothing on the face of the patent does that for the photoreactive substituent required by claims 3–7 and 12–15.
  3. This is the pre‑AIA statute (filed 1990), so § 102(e) applies: a US patent granted on an application filed before the applicant's filing/invention date is prior art as of its filing date. References whose publication postdates 1990‑11‑13 can only be prior art through that route.

3. US patent references cited on the face of US 5,252,743

# Full citation Pub. date Brief description § 102 potential / claims at risk
1 US 4,016,043 — Schuurs et al., Enzymatic immunological method for the determination of antigens and antibodies (cl. 435/6) 1977‑04‑05 Heterogeneous enzyme-immunoassay with antigen or antibody immobilized on a solid carrier; foundational solid-phase immunoassay No § 102 reach — method/apparatus art; no caged biotin compound
2 US 4,371,515 — Chu, Method for forming an isolated lectin-immunological conjugate (436/544) 1983‑02‑01 Lectin–immunoconjugate preparation No § 102 reach — background for the lectin/mannoside embodiment
3 US 4,542,102 — Dattagupta et al., Coupling of nucleic acids to solid support by photochemical methods (435/6) 1985‑09‑17 Psoralen photoreagent + coupling agent to attach nucleic acids to supports; expressly distinguished in the 5,252,743 specification as low-quantum-yield, lacking spatial directability No § 102 reach as to claims 1–15 — no caged biotin. § 102(b) art of record for the general photochemical-immobilization concept; § 103 only
4 US 4,557,998 — Washburn et al., Colorless ligand-releasing monomers and polymers and their use to provide dyes with metal ions (430/367) 1985‑12‑10 Photolabile ("ligand-releasing") colorless monomers/polymers that release a ligand (dye former) on exposure No § 102 reach for the biotin Markush. Closest conceptual art for "photoremovable ligand-releasing group"; § 103 only
5 US 4,562,157 — Lowe et al., Diagnostic device incorporating a biochemical ligand (435/291) 1985‑12‑31 Arylazide photoreactive biochemical ligand immobilized on a device surface; nitrene insertion chemistry. Distinguished in the specification for low coupling efficiency/nonspecific reaction No § 102 reach — distinguished art; § 103 only
6 US 4,576,902 — Saenger et al., Process of making and using a positive working photosensitive film resist material (430/326) 1986‑03‑18 o‑Quinone-diazide positive photoresist imaging; supports the photolithographic-masking teachings No § 102 reach — resist chemistry, cited for imaging art
7 US 4,582,910 — Rosenstein, Method for preparation of 4-halogenonaphthalic acid anhydrides (436/528) 1986‑04‑15 Synthetic method for naphthalic anhydride dye precursors No § 102 reach — synthetic chemistry citation (suspect it is a field-of-search hit; I have not confirmed the examiner's reason)
8 US 4,656,252 — Giese, Amidobiotin compounds useful in an avidin-biotin multiple layering process (530/350) 1987‑04‑07 Discloses biotin NHS ester and caproylamidobiotin (N‑6‑aminohexanoyl biotin) derivatives, i.e., biotin amidated through its carboxyl with an ω‑amino acid, and multilayer avidin/biotin surfaces Closest structural art to the R group of claim 1 (amide/amine terminus at the carboxyl arm; n = 5 ≈ n = 4–6). No anticipation: both ureido nitrogens are unsubstituted (X = Z = H), which claim 1's proviso expressly excludes. § 103 only
9 US 4,709,044 — Sklavounos, Biotin intermediates (548/321) 1987‑11‑24 Discloses 1,3‑diacyl‑4‑(bromomethyl)‑5‑[(5‑alkoxycarbonylpentanoyl) or hexanoyl]‑4‑imidazolin‑2‑ones and the corresponding thieno[3,4‑b]imidazol‑2‑ones, where the 1,3‑acyl is (C₁–C₅)alkanoyl or (C₂–C₅)alkoxycarbonyl; Bunte-salt route to biotin Strongest § 102 candidate against generic claim 1. The "oxycarbonyl of lower alkyl" X/Z alternative is literally an alkoxycarbonyl on N‑1/N‑3 of a biotin-pathway imidazolinone. Caveat: this is a potential-anticipation flag, not a concluded anticipation — I have not performed an element-by-element comparison of Sklavounos's full formula against claim 1's R/U/Y/n variables, and the 5-substituent there is a pentanoyl (not the free/derivatized pentanoic-acid chain contemplated by claim 1). Claims 3–7 and 12–15 (nitroveratryloxycarbonyl/NPOC; specific NVOC compounds) are not met — Sklavounos discloses no nitroveratryl group
10 US 4,719,615 — Feyrer et al., Erasable optical data storage medium (369/284) 1988‑01‑12 Optical disk medium; the 5,252,743 specification cites it for rotating a substrate under a modulated laser/diode source No § 102 reach — expressly cited as a lithography technique reference
11 US 4,722,906 — Guire, Binding reagents and methods (436/501) 1988‑02‑02 Photochemically reactive binding reagents (azidophenyl/benzophenone-type) that photobind to a substrate/counterpart; commercial "PhotoLink"/Immobilizer-type chemistry No anticipation of claims 1–15. Same conceptual class ("photoactivatable binding member for immobilizing biomolecules"), but the mechanism is photogeneration of a reactive species, not photoremoval of a caging group from biotin, and no nitrobenzyloxycarbonyl-substituted biotin is disclosed. I do not have high confidence that this reference is limited to photoreactive (rather than photo-removable) chemistry, so I flag it as the reference most worth reading in full for § 103 purposes
12 US 4,762,881 — Kauer, Photoreactive benzoylphenylalanines and related peptides (525/54.11) 1988‑08‑09 Light-sensitive unnatural amino acid (benzophenone) incorporated into a peptide, then UV-exposed to attach the peptide to a substrate. Distinguished in the specification No § 102 reach for the compound claims; § 102(b)/§ 103 art for the photochemical peptide-immobilization concept
13 US 4,775,545 — Ford et al., Process for producing sweetened fruit (534/560) 1988‑10‑04 Food-processing/sugar chemistry No § 102 reach. I infer it is a field-of-search/saccharide-chemistry citation (the patent claims oligosaccharide and mannoside embodiments); I could not confirm the examiner's stated reason
14 US 4,895,809 — Schlabach et al., Immobilized antigen-antibody displacement process (436/518) 1990‑01‑23 Solid-phase immunoassay using surface-immobilized antibody and labelled-antigen displacement; analyte detection by label loss/accumulation No § 102 reach — supports only the assay/detection embodiments; § 102(a)/§ 103 background
15 US 4,898,951 — Symons, Compounds used as intermediates in the preparations of non-radioactive biological probes (548/303) 1990‑02‑06 Amersham "photobiotin"-family chemistry: nitro-substituted aryl azides (R¹–R⁴ = H, C₁₋₅ alkyl, NO₂, halide, COOH, amino) linked through a hydrocarbyl amine (≥5 C) to a ligand/hapten selected from biotin, iminobiotin and dinitrophenol; photoactivated via aryl nitrene Very close prior art to the photoreactive-biotin concept, but no anticipation of claims 1–15. The biotin unit is attached through its carboxyl arm, leaving both ureido nitrogens unsubstituted → excluded by claim 1's proviso; the photoreactive group sits on the aryl azide linker, not as an N‑oxycarbonyl cage. § 102(a)/§ 103 art
16 US 5,086,185 — Eyer, Process for producing 1,3-substituted tetrahydro-1H-thieno-[3,4-d]-imidazol-2(3H)-on-4-ylidene pentanoic acid ester (548/303) 1992‑02‑04 1,3-disubstituted tetrahydrothieno[3,4‑d]imidazol-2-one (i.e., a biotin ring system carrying substituents on both ring nitrogens), 4‑ylidene pentanoic acid ester Structurally the most on-point "1,3-disubstituted biotin" reference on the face of the patent — but the publication date postdates the 1990‑11‑13 filing date, so it can only be prior art under pre‑AIA § 102(e), and only if its underlying US application was filed before 1990‑11‑13. I do not know that filing date with confidence — verify it before relying on this reference. If it predates, it is a live § 102(e)/§ 103 candidate against claim 1
17 US 5,162,352 — Hall et al., 7-oxabicycloheptyl substituted heterocyclic amide prostaglandin analogs (548/303.7) 1992‑11‑10 Prostaglandin analogs containing a heterocyclic amide No § 102 reach. Same US class (548/303.7) as the biotin imidazolidinones — an art-field citation, and its date postdates the filing date

4. Foreign references cited

# Full citation Pub. date Description § 102 potential
18 EP 0 254 575 A2 — Polymer-coated optical structures 1988‑01‑27 Polymer-coated optical/sensor structures (Godfrey family; cf. US 4,992,385) No § 102 reach — surface-coating/sensor art
19 WO 90/15070 A1 — Very large scale immobilized peptide synthesis (Fodor et al., Affymax) 1990‑12‑13 Light-directed synthesis of peptide arrays on a substrate using photoremovable protecting groups and photolithographic masks — the VLSIPS disclosure Does not anticipate claims 1–15 — no caged biotin compound; the caged species are protected amino acids/monomers. Publication falls between the 1989‑11‑13 priority date and the 1990‑11‑13 filing date, and is a common-assignee document; prior-art status depends on its international filing date and pre‑AIA § 102(e) analysis. High § 103 significance only
20 WO 91/16425 A1 — Method for the light-induced immobilization of biomolecules on chemically "inert" surfaces 1991‑10‑31 Light-induced immobilization of biomolecules on inert supports Not § 102 prior art. Published after the 1990‑11‑13 filing date; its international filing date likewise postdates it. It appears on the face as a prosecution/IDS-type citation, not as § 102 art. If it is being treated as anticipatory art anywhere, that treatment is date-defective
21 GB 615,798 (also cited as GB0615798) 1949‑01‑12 Early British chemical/industrial disclosure; cited generically No § 102 reach. I could not confirm its subject matter; treat as a formal/boilerplate citation until the document is read

5. Non-patent literature cited

The patent also cites 16 journal references. The § 102-relevant ones are:

  • Forster, McInnes, Skingle & Symons, Nucleic Acids Res. 13(3):745–761 (1985) — the original "photobiotin" paper (a photoactivatable biotin–aryl-azide reagent). This is the most important NPL reference: it is the direct antecedent of the "photoactivatable biotin" concept, and the 5,252,743 specification expressly distinguishes it on the ground that photobiotin is derivatized at the carboxylate terminus, "away from the recognition site," and therefore never loses affinity for avidin. Because it lacks the N‑oxycarbonyl cage, it does not anticipate claims 1–15.
  • Patchornik et al., J. Am. Chem. Soc. 92(21):6333–6335 (1970‑10‑21) and Amit et al., J. Org. Chem. 39(2):192–196 (1974) — the founding o‑nitrobenzyl photoremovable protecting-group disclosures; relied on in the specification for the caging concept. Genus-level § 102(b)/§ 103 art; no biotin.
  • McCray et al., Annu. Rev. Biophys. Biophys. Chem. 18:239–270 (1989) — review of photoreactive caged compounds; expressly incorporated by reference in the specification.
  • Wilchek et al., Anal. Biochem. 171:1 (1988) and Bayer & Wilchek, Methods of Biochemical Analysis 26:1–45 (1980) — avidin–biotin technology reviews.
  • Hofmann et al., JACS 100(11):3585–3590 (1978) and Biochem. 21:978–984 (1982); Guire, Meth. Enz. (1976) 280–288; Kohn et al., J. Org. Chem. 42(6):941–948 (1977); Ichimura, J. Pol. Sci. 22:2817–2828 (1984); Lacey et al., Anal. Biochem. 163:151–158 (1987); Roffman et al., Biochem. Biophys. Res. Commun. 136(1):80–85 (1986‑04‑14); Takaya et al., Bull. Chem. Soc. Japan 40:2636–2640 (1967) — supporting photochemistry/immobilization/biotin-synthesis literature. I cannot confirm the subject matter of each from this session and flag them as unread.
  • Fodor et al., Science 251:767–773 (1991‑02‑15) and Dower & Fodor, Ann. Rep. Med. Chem. 26:271–280 (1991) — anomalous citations. Both postdate the 1990‑11‑13 filing date and therefore cannot be § 102 prior art against US 5,252,743. They are common-assignee publications and are most plausibly attributes of the later-filed family members (US 5,451,683 / US 5,482,867) that have been aggregated into the database records for 5,252,743. Do not treat them as anticipatory.

6. Ranked bottom line

  1. No reference on the face of US 5,252,743 anticipates claims 1–15. Every method/apparatus/assay reference is per se incapable of anticipating compound claims; every compound reference lacks the N‑oxycarbonyl caging group (claims 3–7, 12–15) or lacks the ring substitution required by claim 1.
  2. Strongest § 102 candidate (generic claim 1 only): US 4,709,044 (Sklavounos, 1987‑11‑24). Its 1,3‑bis(alkoxycarbonyl) biotin-pathway imidazolinones read on claim 1's "oxycarbonyls of lower alkyl" X/Z alternative. Requires an element-by-element comparison; no nitroveratryl content, so it cannot touch claims 3–7 or 12–15.
  3. Strongest structural-but-date-defective candidate: US 5,086,185 (Eyer, 1992‑02‑04). A literal 1,3‑disubstituted biotin thieno-imidazolone, but post-filing-date; viability depends entirely on its § 102(e) filing date, which must be verified.
  4. Strongest conceptual art (both § 103, not § 102): Forster et al. 1985 (photobiotin); US 4,898,951 (Symons); US 4,722,906 (Guire); US 4,656,252 (Giese); WO 90/15070 (Fodor).
  5. Citations that should be removed from any § 102 analysis for date reasons: WO 91/16425 (1991‑10‑31), Fodor et al. Science 1991, Dower & Fodor 1991, and (unless § 102(e) is established) US 5,086,185 and US 5,162,352.

7. Stated uncertainties

  • I could not read the front-page citation block from the USPTO image record itself; the list above is from three independent non-USPTO mirrors that agree with one another, plus Espacenet's claims text.
  • Filing dates for US 5,086,185 and US 5,162,352 (needed for § 102(e)) are not established here.
  • I have not verified the subject matter of US 4,582,910, US 4,775,545, GB 615,798, or several of the NPL items; I have flagged rather than characterized them.
  • I found no reexamination, interference, or litigation record applying specific art against claims 1–15 in this session, so the § 102 assessments above are my own structural analysis, not an Office or court holding.

Generated 9/27/2026, 7:03:48 PM

Obviousness

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

✓ Generated

I'll ground this analysis in the actual prior-art references cited on the patent page and try to retrieve the claim text, since the fetched Google Patents text for US5252743 includes the description and abstract but not the claims themselves.

I now have the granted claim set (compound claims 1–15). Let me verify the remaining cited prior-art references and check whether any method claims exist.

Obviousness analysis — US 5,252,743 (Barrett et al., "Spatially-addressable immobilization of anti-ligands on surfaces")

0. Preliminary: what is actually claimed (and a source caveat)

The Google Patents page you supplied (https://patents.google.com/patent/US5252743/en) contains the abstract, the "Definitions," and the description, but not the claim set. I retrieved the granted claims from two independent mirror/source pages:

Both show 15 claims, all of them composition-of-matter claims, not method claims. Claim 1 is "A caged binding member compound having the formula ##STR30##," wherein

  • X and Z = H or "oxycarbonyls of lower alkyl, aryl, and benzyl groups," provided that when X is H, Z is not H or methyloxycarbonyl; when Z is H, X is not H or methyloxycarbonyl; and when X or Z is methyloxycarbonyl, R is not methyl formate;
  • R = H, lower alkyl, aryl, lower alkyl formate, aryl formate, formamide, N-alkylformamide, N-succinimidyl, hydroxyl, alkoxyl, thiol, thioether, disulfide, hydrazide or amine; U = O, S or NH; Y = sulfur, oxygen, methylene, carbonyl, sulfinyl, sulfonyl, or two hydrogens; n = 1–7; plus acid addition salts.

Claims 2–4 and 8–11 are generic sub-genuses (U=O/Y=S/n=4 for biotin itself; nitroveratryloxycarbonyl; ring-disubstituted benzyloxycarbonyl; dimethoxy; dimethyl). Claims 5–7 and 12–15 are species: NVOC-biotin methyl ester, NVOC-biotin p-nitrophenyl ester, the nitropiperonyloxycarbonyl (NPOC) analog, and four named structures.

Important consequence: because the '743 claims are compound claims, the §103 case is a structural-obviousness case (the In re Dillon / In re Baird line), not a method case. The method claims of this family live in the continuing applications — US 5,482,867 (https://patentimages.storage.googleapis.com/19/9f/02/e37b972c843520/US5482867.pdf) and US 5,451,683 — which the record identifies as claiming priority from this same disclosure. Note literally: the text of US 5,482,867 states its parent was "Ser. No. 07/612,571, filed Nov. 13, 1990, now U.S. Pat. No. 5,252,743," whereas the application number printed on the '743 page is 07/612,671. I am not correcting either number; flagging the discrepancy as printed.

I also do not have the file wrapper, so I cannot state what the examiner actually cited. What follows is an analytical assessment of the references that the page itself puts in play.


1. The prior art the page itself identifies

The "Prior Art" content on this page consists of (i) the operative keywords ("biotin, ligands, binding, ligand, compound") and (ii) the Background of the Invention citations, supplemented by prior art discussed in the description:

Ref (as printed on the page) What it teaches
U.S. Pat. No. 4,282,287 (Giese; verified: https://patents.google.com/patent/[US4282287A](/patent/US4282287A)/en) Avidin–biotin multiple-layer system; biotin-NHS ester covalently attached to a polymer surface, avidin bound to surface biotin, biotinylated extender/anti-ligand bound to avidin; expressly lists streptavidin as an avidin analog and desthiobiotin/biotin sulfone as biotin analogs; states the complex "persists when biotin is attached by means of its carboxyl group to another molecule."
U.S. Pat. No. 4,562,157 (Lowe & Earley; https://patents.google.com/patent/[US4562157A](/patent/US4562157A)/en) "BiochemFET": photoactivatable group (aryl azide) covalently bound to a silica/silicon-nitride surface, photo-exposed selectively through a mask, then biochemical species (hapten, antigen, antibody, lectin, enzyme) bonded only in selected areas; expressly contemplates "printed circuits for proteins."
U.S. Pat. No. 4,762,881 (Kauer; verified as "Photoreactive benzoylphenylalanines and related peptides," https://uspto.report/patent/grant/4762881) Light-sensitive unnatural amino acid groups used to attach polypeptides to a solid substrate on low-energy UV exposure.
U.S. Pat. No. 4,681,870 Silica matrix bearing free amino/carboxyl groups, carbodiimide coupling to proteins.
U.S. Pat. No. 4,542,102 (Dattagupta et al.; https://patents.google.com/patent/[US4542102](/patent/US4542102)) Photochemical coupling of nucleic acids to supports; cyanogen bromide/diepoxide surface activation; amine-derivatized surfaces.
U.S. Pat. No. 4,719,615 Rotating substrate under a modulated laser/diode light source (maskless spatial addressing).
Patchornik, J. Am. Chem. Soc. (1970) 92:6333; Amit et al., J. Org. Chem. (1974) 39:192; McCray et al., Annu. Rev. Biophys. Biophys. Chem. 18:239-70 (1989) — all cited in the description The o-nitrobenzylic photolabile protecting groups (nitrobenzyl/NVOC family) and the caged-compound principle: install a photolabile group on a biologically active molecule so activity is destroyed until light removes it.
Calbiochem Catalog (San Diego, 1989) pp. 244–247 (cited in the description) Panel of commercially available photoremovable protecting groups, including NVOC, NPOC, DDZ and 1-pyrenylmethyl — the very groups recited in claims 3–11.
Bayer et al., Methods of Biochemical Analysis, vol. 26 (1980) 1-45; N. Green, "Avidin," Adv. Protein Chem. 29:85-133 (1975) Derivatization of biotin at the free carboxyl end; catalogue of biotin analogs; structure–activity: the ureido/imidazolidone ring is the avidin-recognition element.
Nerbone et al., Nature (1984) 310:74 (as printed; the well-known paper is Nerbonne et al.) Photoactivatable ("caged") cAMP — precedent for caging a ligand recognized by a binding protein.
Sze, VLSI Technology (1983); Flanders et al., App. Phys. Lett. (1977) 31:426-428 Photolithographic masking/alignment technology for directing light to precise, known locations.

2. Governing standard and the PHOSITA

Graham v. John Deere; KSR Int'l v. Teleflex (obvious to try with a finite number of identified, predictable solutions; predictable use of prior-art elements according to their established functions; design incentives/market pressure); In re Dillon (a prima facie obviousness case against a new chemical compound can rest on prior art teaching the structure and a contemplated utility); In re Baird/In re Jones (small, structurally defined genera with predictable properties).

The priority date is Nov 13, 1989 (CIP filing Nov 13, 1990), so the §102(b) critical date is Nov 13, 1988 and §102(a)/(e) art runs to Nov 13, 1989. (Note the 1989 Calbiochem catalog's exact publication date would matter.)

PHOSITA: a Ph.D.-level synthetic/biological chemist (or a small team including a peptide/heterocycle chemist and a bioconjugate biochemist) with a few years' experience in (a) avidin–biotin surface chemistry and (b) photolabile protecting-group chemistry.


3. The core combination that renders claim 1 prima facie obvious

Green (1975) + Bayer (1980) + Patchornik (1970)/Amit (1974)/McCray (1989), optionally + Calbiochem (1989).

  1. Green and Bayer supply the complete structure of the lead compound (biotin), the synthetic handle (the carboxyl terminus, where derivatization does not disturb binding), and — critically — the structure–activity teaching that substituents on the ureido/imidazolidone nitrogen(s) abolish avidin binding.
  2. Patchornik and Amit supply the structural class of substituent to place there: o-nitrobenzylic carbamates (including the 3,4-dimethoxy-6-nitrobenzyl = nitroveratryl group) that are installed on amines and removed by near-UV light. McCray supplies the reason to do it (reversible inactivation of a ligand until photolysis) and, via caged cAMP and caged nucleotides, proves the technique works on small molecules bound by proteins.
  3. Calbiochem (1989) supplies a finite, enumerated catalogue of the very carbamate groups recited in claims 3–11 (NVOC, NPOC, DDZ, 1-pyrenylmethyl).

Motivation, in KSR terms: this is the "predictable use of prior art elements according to their established functions." The protecting group is asked to do exactly what it is known to do (mask an amine until irradiated); the amine chosen is exactly the one long known to control avidin affinity. The result — a biotinyl compound that is a poor avidin binder until photolyzed — is the necessary consequence of two known teachings, not an unpredictable discovery. Claim 1's R/U/Y/n variables are conventional ester/amide/heteroatom variants of biotin itself; the ring-disubstituted benzyloxycarbonyl and nitroveratryl species are within a small, identified set of photolabile carbamates.

A second, independent route to claim 1 (and worth noting because of the claim's provisos): claim 1's X/Z genus is "oxycarbonyls of lower alkyl, aryl and benzyl" — i.e., ordinary carbamate protecting groups such as Boc and Cbz, not just photolabile ones. The claim does not require that X or Z be photoremovable. To the extent N-carbamoylated biotins (e.g., Boc- or Cbz-protected, or methyloxycarbonyl-biotin and its methyl ester) were already known, claim 1's genus would be a matter of routine variation of known biotin derivatives. The provisos ("when X is hydrogen, Z is not hydrogen or methyloxycarbonyl"; "when X or Z is methyloxycarbonyl, R is not methyl formate") read like claim-narrowing amendments inserted to avoid precisely such a known compound, and the infringement/validity analysis should begin by obtaining the file wrapper to identify it.


4. The second combination — supplying the purpose (why make the compound at all)

Giese '287 + Lowe '157 (+ Sze or '615) + the caging art above.

  • Giese '287 gives the whole architecture that the patent uses downstream: surface → biotin → avidin → biotinylated anti-ligand, with streptavidin expressly named and biotin analogs expressly contemplated.
  • Lowe '157 supplies the missing objective: spatially selective, mask-directed attachment of different biochemical ligands to predefined areas of one surface ("printed circuits for proteins"). It even uses a silica surface and a photo-generated attachment step.
  • Sze (and '615 for maskless laser writing) teaches that light can be directed to "relatively small and precisely known locations."
  • The specification itself concedes the known problem: "there exists a need for improved methods for attaching a broad range of anti-ligands to predefined regions of a solid support surface," and criticizes '157's nitrene chemistry for "low coupling efficiencies," non-specific reactions, and '102 for "low quantum yields… lacks spatial directability."

A POSHITA reading Lowe would ask: what photo-switchable capture system can produce patterned protein attachment without relying on a diffusible reactive nitrene? The obvious answer from Giese is the biotin–avidin pair, which is non-covalent, high-affinity and self-assembling — provided the biotin can be switched off. Caging the ureido nitrogen (per Green + Patchornik) supplies that switch. The final product of that chain of reasoning is claim 1's compound and its species claims.


5. Dependent claims

Claim(s) Why obvious
2 (U=O, Y=S, n=4) Simply selects biotin itself as the scaffold — taught by Green/Bayer.
5 (NVOC-biotin methyl ester), 6 (NVOC-biotin p-nitrophenyl ester) NVOC is the archetypal nitroveratryl carbamate of Patchornik; the methyl and p-nitrophenyl esters are the two most conventional biotin carboxyl derivatives — Bayer and Giese expressly use biotin-NHS ester and caproylamidobiotin-NHS ester. Routine optimization of an ester leaving group for amine coupling.
7 (NPOC) 6-Nitropiperonyloxycarbonyl is a homolog of NVOC listed in the very Calbiochem pages the spec cites — a finite, predictable alternative.
8–11 (ring-disubstituted benzyloxycarbonyl; methoxy; methyl) The DDZ = "α,α-dimethyl-dimethoxybenzyloxycarbonyl" group is itself listed by the spec among known photosensitive protecting groups; varying ring substituents on a nitrobenzyl carbamate is the definition of predictable variation in this art. In re Baird caution: a large Markush does not automatically make every species obvious, but here the substituent set (H, alkyl, alkoxy, halogen, nitro) is fully conventional and the properties are known.
12–15 (named structures) Same analysis; each is a specific nitroveratryl/nitrobenzyl carbamate of biotin.

6. Rebuttal / non-obviousness considerations that should be tested

  1. Provisos are unexplained in the public record. Whether they were added for §102 or §103 reasons materially affects the strength of the compound claims; the file wrapper is essential.
  2. Criticism of the prior art is a two-edged sword. The specification's attacks on '157 and '102 are admissions that the goal was recognized; under KSR, a defect in an approach motivates finding a better one rather than teaching away.
  3. Unexpected results. The 3→7-orders-of-magnitude affinity differential the spec demands (activated vs. caged Ka) is a real, quantified requirement. If applicants can show that ordinary carbamate protection fails to depress avidin binding enough (steric/electronic thresholds) and that the NVOC/NPOC/DDZ selection was empirically required, that is a genuine §103 argument. The subsequent literature (Sundberg, Barrett, Pirrung, Stryer et al., "Spatially-Addressable Immobilization of Macromolecules on Solid Supports," J. Am. Chem. Soc. 1995, 117, No. 49, p. 12053 — as retrieved) lists "synthesis of biotin analogues with greatly reduced binding affinity… until after photodeprotection" as one of five non-trivial experimental prerequisites, which supports the inventors' position.
  4. Secondary considerations. Commercial success of Affymetrix microarrays and the long-felt need for spatially addressable multiplexed arrays are the natural objective indicia, but the nexus is weak as to compound claims 1–15: the array franchise is more plausibly tied to the method claims (US 5,482,867 / 5,451,683) and to the VLSIPS patents of the separate Affymax/Affymetrix family (e.g., US 5,143,854, priority June 7, 1989) than to a genus of caged biotin esters. Any "licensing/industry praise" evidence should be scrutinized for this reason.
  5. Timing caveats. WO 89/10977 (Southern, "Analysing polynucleotide sequences," published Nov 16, 1989 — three days after the Nov 13, 1989 priority date) is not on its face §102(a)/(b) art against these claims; do not assume it into an obviousness combination without an earlier priority/§102(e) analysis. The same discipline applies to the Calbiochem 1989 catalogue.

7. Bottom line

The strongest prima facie §103 case against claims 1–15 is the three-way combination Green (1975) / Bayer (1980) [biotin structure, carboxyl handle, ureido ring = avidin-recognition element] + Patchornik (1970) / Amit (1974) / McCray (1989) / Calbiochem (1989) [o-nitrobenzylic photolabile carbamates, and the caging rationale], motivated by Lowe '157 + Sze [mask-directed, spatially selective attachment of ligands to a surface] and enabled in practice by Giese '287 [biotin-NHS/avidin surface architecture]. That combination renders the generic claim and the NVOC/NPOC/DDZ species claims obvious as predictable uses of known elements, and it does so without needing any reference to render the compounds anticipatory.

Whether that case survives depends on (a) the unidentified prior art behind claim 1's provisos, (b) the file-wrapper record of why the applicants believed ordinary carbamate protection of the ureido ring destroyed avidin binding with sufficient sensitivity, and (c) whether the objective indicia can be tied to these compounds rather than to the related method/VLSIPS patents.

This is a technical analysis, not a legal opinion; I have not reviewed the prosecution history, and the claim text above was obtained from third-party mirrors rather than from the page you provided, whose fetched text omits the claims.

Generated 9/27/2026, 7:04:04 PM

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