US 5153319

I'll search for the specific patent and any related litigation.

Let me dig deeper on the claims, family, and any litigation.

Verification of the Identifier

US 5,153,319 resolves to a single, unambiguous record. I did not find any evidence of a similar-numbered patent being confused with it, and I have deliberately not substituted any adjacent numbers (e.g., 5,132,418 or 5,033,190). Search results were consistent with the authoritative full text supplied.

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Bibliographic Summary — US 5,153,319 A

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Abstract (verbatim)

"New and useful intermediate nucleotides bound to an inorganic polymer support, including the preparation thereof, and processes for the conversion to oligonucleotides which are especially useful for the synthesis of polynucleotides, particularly ribonucleic (RNA) and deoxyribonucleic (DNA) acids, are described."

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Plain-Language Overview of the Disclosure

The patent is a foundational solid-phase oligonucleotide synthesis document (the "Caruthers" family). In plain terms it teaches:

1. A modified inorganic polymer support — preferably macroporous silica gel (e.g., Vydac A, TP silica; 5–1000 µm particles, ~50–2000 Å pores) — carrying a covalently bound first nucleoside.
2. How to make it: treat silica with an aminoalkyl-trialkoxysilane (e.g., 3‑aminopropyltriethoxysilane) in refluxing toluene; cap residual silanols with trimethylchlorosilane; then attach a nucleoside via a dicarboxylic acid (succinic anhydride preferred; also glutaric, adipic, phthalic, maleic) through the nucleoside's 3′‑OH, leaving the 5′‑OH free. Unreacted amine groups are blocked (acetic anhydride/pyridine; morpholine treatment for succinylated amines).
3. The synthesis cycle on that support: (a) condensations with an activated nucleoside phosphite (methyl phosphorodichloridite-derived; the tetrazolide is preferred) to form a triester phosphite linkage; (b) capping of unreacted 5′‑OH (diethoxytriazolylphosphine, or acetic anhydride/DMAP); (c) iodine/2,6‑lutidine oxidation of phosphite to phosphate (deferred oxidation is explicitly taught to reduce yields); and (d) removal of the 5′‑trityl blocking group.
4. Detritylation with a Lewis acid — uniquely, ZnBr₂ in nitromethane (15–30 min) is claimed as superior to protic acids because it is fast and avoids depurination of purine-containing products. BF₃, AlCl₃ and TiCl₄ are named as alternatives; the specification states the procedure is also useful for pure solution-phase synthesis.
5. Cleavage/recovery: mild base (concentrated NH₄OH) hydrolyzes the ester linkage to release the oligonucleotide; methyl groups are removed from phosphotriesters with triethylammonium thiophenoxide in dioxane; N‑acyl groups are removed at 50 °C; DMT groups by aqueous acetic acid. Reverse-phase HPLC of the 5′‑O‑DMT oligonucleotide is the preferred purification.
6. An automated apparatus (Fig. 1) with programmed multi-port valves, reservoirs held at −78 °C for the phosphite adducts, a recycle loop through the silica column, and UV monitoring — with a step-by-step protocol in Table I.
7. Reported performance: ≥95 % per-addition yields in ~2–3 h per cycle; products up to 10–30 nucleoside units (working examples: d(T)₉, d(T‑C‑T‑C‑T‑C‑T‑T‑T), d(T‑C‑A‑C‑A‑A‑T‑T)), verified by snake-venom phosphodiesterase digestion and 5′‑³²P/T4‑kinase gel electrophoresis.

Cited background art in the specification: Köster, Tetrahedron Letters 1527–1530 (1972); Letsinger & Lunsford, JACS 98:12, 3655–3661; Amarnath & Broom, Chem. Rev. 77, 183–217 (1977); and U.S. Pat. Nos. 3,519,538; 3,419,517; 3,652,761; 3,669,841.

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Independent Claims — Important Caveat

I could not retrieve the verbatim claim text of US 5,153,319 from any source I searched, and the authoritative text supplied to me was truncated mid-specification (it ends at "silica, po…") and does not include the claims. I will therefore be explicit rather than fabricate:

• The only authoritative claim language I recovered belongs to the parent/sibling case — the Biotechnology Law Report litigation notice (Appl. No. 247,144, filed Mar. 24, 1981) prints independent claims 1, 7, 13, 18, 34 and 43, which are:
• Claim 1 — a modified inorganic polymer of a given formula, where the inorganic polymer is linked to the 3′‑ or 5′‑O‑ of a nucleoside through a base-hydrolyzable covalent bond; R = H or blocking group; R₁ = hydrocarbon radical up to 10 carbons; B = nucleoside/deoxynucleoside base; A = H or OR.
• Claim 7 — the same genus but limited to linkage through the 3′‑O via an ester linkage.
• Claim 13 — an inorganic polymer bearing an oligonucleotide/deoxyoligonucleotide covalently bound through an ester linkage formed through the 3′‑OH of the initial nucleoside, with the terminal nucleoside attached through a phosphite or phosphate triester linkage and the 5′‑O substituent being H or a blocking group.
• Claim 18 — a process of condensing the 3′‑ or 5′‑OH of a support-bound nucleoside/oligonucleotide with a phosphite compound where X = Cl, Br, or a secondary amino group.
• Claim 34 — a process of condensing a silica-bound nucleoside (bound via —Z₁NHCOZCO—, Z and Z₁ = alkylene up to 5 C) with a nucleoside phosphite compound.
• Claim 43 — a process for producing polynucleotides by condensing a 3′‑ or 5′‑OH of a nucleoside on a functionalized inorganic polymer with the reaction product of a nucleoside and a blocked phosphodichloridite.

Because US 5,153,319 is described in its own text as a continuation of the same application line, its independent claims are very likely to be a related but not identical set covering the support-bound nucleoside compositions and the phosphite-trioxide condensation/capping/oxidation/detritylation process. I cannot state the exact independent claim numbers or wording for 5,153,319 itself with confidence.

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Litigation / CAFC 2026 Dockets

• Google Patents flags this family as having litigation, linking to Darts‑ip family 25297985. I could not retrieve the case caption, court, or docket numbers from that link or from any other source in these searches.
• A Justia "PEB DNA Synthesis and Purification Patents" reference groups US 4,997,927 (GBF) with 4,458,066, 5,132,418, 5,153,319, 4,973,679 ("Caruthers Process") and 4,415,732, 4,668,777, 4,500,707 ("Caruthers Reagents") as a licensing/enforcement portfolio — consistent with the historically litigated Caruthers/University Patents gene-machine patent estate.
• I found no 2026 Court of Appeals for the Federal Circuit docket, opinion, or appeal involving US 5,153,319. I must also flag the practical point that the patent's own record shows anticipated expiration on 2009‑10‑06 and current status "Expired – Fee Related," so a live 2026 CAFC appeal on this patent would be highly unusual. I cannot confirm or deny any such 2026 activity; treat any 2026-docket claim as unverified.

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Stated Uncertainties

1. Parent-application inconsistency. The supplied text states: "This is a continuation of application Ser. No. 601,813 filed Jun. 18, 1984, now U.S. Pat. No. 4,458,066." Search results contradict this literally: US 4,458,066 is recorded as application 247,144, filed 1981‑03‑24 (priority 1980‑02‑29), issued 1984‑07‑03; whereas 5,132,418 is recorded as filed 1984‑06‑18 with the same inventors and assignee. I am reporting the patent's own text verbatim without correcting it, but the parent identification is internally suspect.
2. Priority date. Google Patents lists the filing date as 1986‑03‑31 (treated as the priority date), while one aggregator shows a priority date of 1986‑03‑30. Minor, unconfirmed.
3. Inventor's CV labeling. A University of Colorado CV entry labels US 5,153,319 as "Phosphoramidite Compounds and Processes," which conflicts with the official title "Process for preparing polynucleotides." The official title is corroborated by Google Patents, EveryPatent, uspto.report and a Justia citation table ("5153319 | October 6, 1992 | Caruthers et al."). I treat the CV label as an error but note it.
4. Assignee address is given inconsistently (Norwalk, Conn. vs. Westport, CT) across secondary aggregators; I did not obtain a primary USPTO assignment record.
5. Claims of 5,153,319 specifically were not obtainable — see the caveat above.

Sources: https://patents.google.com/patent/US5153319/en; https://uspto.report/patent/grant/5153319; http://www.everypatent.com/comp/pat5153319.html; https://patents.justia.com/patent/[10815291](/patent/10815291); https://dictionary.contracts.justia.com/peb-dna-synthesis-and-purification-patents/; https://no.espacenet.com/publicationDetails/biblio?CC=US&NR=[4458066A](/patent/4458066A); https://idiyas.com/patent/badge/5132418; https://portal.unifiedpatents.com/patents/patent/US-[11680083](/patent/11680083)-B2 (citing US‑5153319‑A, 1986‑03‑30, University Patents Inc).

I'll search for litigation involving US 5,153,319 specifically.

Let me search for additional litigation and the specific case dockets.

Let me dig into the Delaware case docket and any post-2004 developments, plus check the litigation databases.

Bottom line

Yes — US 5,153,319 ("Process for preparing polynucleotides," Caruthers & Matteucci, University Patents Inc.; filed 1986-03-31; issued 1992-10-06) has been asserted in litigation. Based on my searches, I found one infringement action in which the '319 patent was asserted, one declaratory-judgment action that followed it and also put the '319 patent at issue, and several 1980s-era suits on the earlier patents in the same Caruthers/Matteucci family that predate the '319 patent's issuance and therefore could not have involved the '319 patent itself.

Caveats up front (per your strict rules):

• I did not get direct access to PACER or to the Unified Patents litigation caselist (https://portal.unifiedpatents.com/litigation/caselist); those sites did not return in my searches. My findings come from court opinions (CourtListener, Justia, Casetext, vLex), SEC filings, and trade press.
• I could not confirm the Delaware docket number for the July 2000 action, and I could not confirm the final disposition of the S.D.N.Y. action after the January 2004 opinion. I flag these as gaps rather than guessing.
• Your instruction to interpret identifiers literally matters here: some renderings of the S.D.N.Y. opinion (e.g., the CourtListener Harvard PDF of 219 F. Supp. 2d 390) print the asserted patents as "5,158,319" and "4,978,679," which are not the patents at issue. Other renderings of the same opinion (Justia, Casetext, calculators.law) correctly give 5,153,319 and 4,973,679. I treat 5,153,319 as the patent at issue and note the "5,158,319" string as a rendering error in that source, not a separate patent.

1. Applera Corp. et al. v. Affymetrix, Inc. (the infringement suit asserting '319) — D. Del.

Sources: Affymetrix, Inc. v. PE Corp., 219 F. Supp. 2d 390 (S.D.N.Y. 2002) — https://law.justia.com/cases/federal/district-courts/FSupp2/219/390/[2447770](/patent/2447770)/ ; Affymetrix, Inc. v. PE Corp., 306 F. Supp. 2d 363 (S.D.N.Y. 2004) — https://calculators.law/caselaw/decisions/5Mg8OGpxX8Vn/affymetrix-inc-v-pe-corp ; BioCentury, "Affymetrix, PE Biosystems enabling technology news" — https://www.biocentury.com/article/[189833](/patent/189833)/affymetrix-pe-biosystems-enabling-technology-news ; Affymetrix SEC Form 10-Q describing the July 5, 2000 filing — https://www.sec.gov/Archives/edgar/data/[913077](/patent/913077)/000104746903027625/a2116470z10-q.htm

2. Affymetrix, Inc. v. PE Corp. (N.Y.), Competitive Technologies, Inc., Applera Corp., Perseptive Biosystems, Inc. — S.D.N.Y.

Note on the '319 patent's treatment in this case: the Jan. 2004 anticipation holding expressly covered only claims of the '066 and '418 patents — not the '319 patent. The inequitable-conduct theory, however, was pleaded against '319 as well, on the theory that '319 is a continuation of '066, so non-disclosure/best-mode defects in the '066 prosecution would carry over. See the discussion of the '707/'418/'319 patents in 219 F. Supp. 2d 390.

Sources: https://law.justia.com/cases/federal/district-courts/FSupp2/219/390/2447770/ ; https://www.courtlistener.com/opinion/2447770/affymetrix-inc-v-pe-corpny/ ; https://www.courtlistener.com/opinion/[2526031](/patent/2526031)/affymetrix-inc-v-pe-corp/ ; http://g.casetext.com/case/affymetrix-inc-v-pe-corp-ny ; https://case-law.vlex.com/vid/affymetrix-inc-v-pe-890279104

3. Related (but NOT '319) litigation — for context only

These are family/portfolio cases that preceded the '319 patent's 1992 issuance and therefore cannot have involved US 5,153,319. I list them so you do not mistakenly attribute them to '319:

• Millipore Corp. v. University Patents, Inc., 682 F. Supp. 227 (D. Del. 1988) — declaratory-judgment action by Millipore against UPI (with Applied Biosystems/ABI sublicense pressure and a parallel California ABI action). Pre-'319. https://app.midpage.ai/document/millipore-corp-v-university-patents-[1583542](/patent/1583542)
• University Patents, Inc. v. Biosearch, Inc. and University Patents, Inc. v. Biosyntech (1985–1986), with Biosearch antitrust/patent-misuse counterclaims against Applied Biosystems — reported in Biotechnology Law Report blotters (BLR 406/407/432/444). Pre-'319. These appear to concern the earlier '066/'707/'732 family.
• Ogilvie interference declared Sept. 17, 1982 against UPI's '066 application (abandoned by Ogilvie April 1983) — a PTO interference, not district-court litigation. Pre-'319. A further interference in 1998 is referenced in the record but its parties and outcome are not established by my sources.

Also of note: Google Patents' page for US5153319 flags a Darts-IP "First worldwide family litigation filed" link (https://patents.darts-ip.com/?family=25297985...), which is consistent with the family having litigation history, but that page is a litigation-data aggregator indicator, not a case record.

Verification gaps I am flagging rather than filling

1. Delaware docket number for Applera/Competitive Technologies v. Affymetrix (filed July 5, 2000) — not confirmed.
2. Post-January-2004 disposition of S.D.N.Y. 01 Civ. 0634 (NRB) — not confirmed. Any statement that the '319 patent was ultimately held invalid or unenforceable would be speculation on my part.
3. Any additional suits asserting '319 specifically (e.g., against other synthesizer/reagent vendors) — none surfaced in my searches, but I could not query PACER or the Unified Patents caselist directly, so I cannot rule them out.
4. In the Jan. 2004 opinion, the '319 patent was in suit but the anticipation holding did not reach its claims; I found no separate validity or infringement ruling on the '319 claims themselves.

If you need the two gaps closed (Delaware docket number and final S.D.N.Y. disposition), the right next steps are a PACER docket pull for S.D.N.Y. 1:01-cv-00634-NRB and a Delaware C.A. docket search for July 2000 filings by Applera/Competitive Technologies against Affymetrix.

I'll verify the structured "no PTAB activity" default against live sources before writing anything up.

Now let me check the PTAB docket directly and look for any post-issuance review of this patent (including pre-AIA reexamination, which would also appear in the file history).

Let me check for any Federal Circuit or district court treatment of this specific patent, and any post-issuance administrative review.

Proceedings overview

Total AIA trial proceedings on US 5,153,319: zero. The structured PTAB dataset in this prompt (USPTO Open Data Portal) returns no AIA trial proceedings, and independent searching of PTAB docket material (PTAB E2E / PTACTS, CourtListener RECAP PTAB filings) surfaces no IPR, PGR, or CBM naming this patent. Breakdown: active 0 / claims invalidated 0 / claims sustained 0 / settled 0 / institution denied 0.

The bottom line for a defendant is unusual and stronger than any IPR result: this patent is not merely un-IPR'd, it is expired. Google Patents lists an application filing date of 1986-03-31, publication of US5153319A on 1992-10-06, an anticipated expiration of 2009-10-06, and a current legal status of "Expired – Fee Related" (US5153319A). AIA trial practice did not exist in usable form until the IPR regime took effect on 2012-09-16 — nearly three years after this patent's term ran out. The absence of PTAB activity here is therefore structural, not probative of validity. Do not read it as "the patent survived attack"; read it as "the patent was already dead by the time the PTAB could have been used on it."

There is a real, separate defensive posture, though: the patent belongs to the Caruthers/Matteucci "C & M" family, and a sister patent in the same family ('066, and '418) had claims invalidated on summary judgment in Affymetrix, Inc. v. PE Corp., 306 F. Supp. 2d 363 (S.D.N.Y. 2004), on exactly the prior art that the family's prosecution history is shadowed by. That is where a defendant should look, and I cover it below.

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No proceeding-level entries

Because the canonical structured list is empty, there is no proceeding card to populate. Rather than fabricate one, here are the near-miss dockets I checked and excluded — reviewers frequently mistake these for this patent:

None of these involve University Patents Inc. or Caruthers/Matteucci. I found no proceeding that does.

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Cross-jurisdiction picture (the substantive defenses that do exist)

District court / Federal Circuit history involving this patent

• Filing & provenance: US 5,153,319 (Caruthers & Matteucci) issued 1992-10-06 from an application filed 1986-03-31, assigned to University Patents Inc. (UPI) per Google Patents. The printed specification states it is a continuation of Ser. No. 601,813 filed 1984-06-18, "now U.S. Pat. No. 4,458,066" — a statement I flag as internally inconsistent (the '066 patent is reported as issuing 1984-07-03 from a March 1981 CIP), and one worth a priority-chain audit if you ever litigate a sibling.
• Affymetrix, Inc. v. PE Corp. (N.Y.), 306 F. Supp. 2d 363 (S.D.N.Y. 2004) — declaratory judgment action on five family patents including '319. Holding: "plaintiff's motion for summary judgment that certain claims of patents '066 and '418 are anticipated by the 1980 article under 35 U.S.C. § 102(b) is granted. Accordingly, we hold that claims 1-13 and 18-43 of the '066 patent and claims 1-7 and 21-24 of the '418 patents are invalid." Note precisely: the '319 claims were not adjudicated invalid in that opinion. The court granted summary judgment of anticipation only as to '066 and '418; it denied the § 101/§ 112 motion against '679, and denied the inequitable conduct motion, finding a genuine issue of material fact as to good faith and directing the parties to appear on 2004-03-04. Record: CourtListener opinion 2526031.
• The 1980 Tetrahedron Letters article — "The Synthesis of Oligodeoxypyrimidines on a Polymer Support," Caruthers & Matteucci, Feb. 19, 1980 — is the art the court found to be a § 102(b) bar to the broadened CIP claims, on the theory that the parent application's silica-gel-only disclosure did not support the later "inorganic polymer" and "hydrocarbyl phosphorodichloridite" genus claims (Lockwood written-description analysis). '319 issued from the same C & M lineage and its specification claims broad inorganic-polymer support and hydrocarbyl protecting-group scope (see the '319 text: "inorganic polymers … silica, porous glass, aluminosilicates, borosilicates, metal oxides such as alumina and nickel oxide, and various clays"). That is the same § 102(b)/§ 112 exposure, untested for '319.
• Millipore Corp. v. University Patents, Inc. — an earlier DJ/declaratory-judgment dispute regarding UPI's assertion program (CourtListener opinion 1583542); background only, no '319 claim construction.
• Competitive Technologies, Inc. (formerly UPI) held title to the family per the Affymetrix record, with PE/PerSeptive holding exclusive enforcement rights — an ownership split a defendant should confirm today via the USPTO Assignment database.

Interferences (pre-AIA, PTO)

• The Ogilvie interference (declared 1982-09-17; dissolved 1983) and "another interference in 1998" are recounted in the Affymetrix opinion. These are pre-AIA interference proceedings, not AIA trials; the interference file is not the same as a PTAB AIA docket and does not appear in ODP AIA trial data.

Licensing context

• '319 appears in the "PEB DNA Synthesis and Purification Patents" license listing alongside '066, '418, '679, '927 — i.e., it was monetized through the Applied Biosystems/PerSeptive licensing program.

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Strategic summary

Claim status. No claim of US 5,153,319 has ever been canceled, confirmed, or construed in a PTAB final written decision — there is no FWD to quote, and I will not attribute claim numbers to a decision that does not exist. Every claim is, on the public record, UNCHALLENGED at the PTAB and UNTESTED as to validity in a merits ruling. What is established: (i) the patent's term is over (anticipated expiration 2009-10-06; status "Expired – Fee Related"), and (ii) the same prior art that killed '066 and '418 claims in 2004 ascribes a written-description/§ 102(b) problem to the family's broadened genus claims. If a demand letter today quotes claims of '319, the first question is not "what did the PTAB do" — it is "what conduct could still be actionable, and was any suit filed within § 286's six-year window?"

Estoppel landscape. With no IPR/PGR/CBM, § 315(e)(2) estoppel is a non-issue — no petitioner has any estoppel to assert against you, and no ground is foreclosed to you. Every prior-art ground remains available: the 1980 Tetrahymena-Letters article, the Letsinger/Lunsford phosphotriester work discussed in the '319 background (JACS 98:12, 3655-3661), the Köster Tetrahedron Letters 1972 silica-trityl work that the '319 specification itself distinguishes, and the § 112 written-description attack the S.D.N.Y. adopted for the siblings. Note the mirror-image consequence: because IPR is unavailable/expired and no FWD exists, you would litigate validity the old way (district court, § 282 burden on you, clear-and-convincing for invalidity) rather than under the IPR preponderance standard. Practically moot given expiry and the § 286 bar.

Pattern signals. No repeat petitioner (none exists). No Patent Owner appeal to the Federal Circuit on any '319 claim construction or PTAB ruling — I found no CAFC docket involving this patent. No defensive aggregator (Unified Patents, RPX) appears in the chain; the monetization program here was UPI → Competitive Technologies → Applied Biosystems/PerSeptive licensees. The only litigation "family" flag on the Google record is the Darts-IP entry (family 25297985) — that is the pre-AIA district court/ITC track, not PTAB.

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Recommended next steps

• If you are the defendant: the short answer is that this patent cannot support an infringement claim for any conduct on or after 2009-10-06, and any pre-expiry claim is long outside the § 286 six-year lookback (which closed 2015-10-06). Ask the asserting party for (a) the operative license/ownership chain (UPI vs. Competitive Technologies vs. PE/PerSeptive enforcement rights) and (b) the last date of alleged infringement. If they cite the patent as live, that is a misrepresentation of an expired patent.
• If you must brief invalidity anyway (e.g., for a DJ or a fee motion), lead with the C & M family precedent: quote Affymetrix, 306 F. Supp. 2d at 373-74 — "we find that all claims in defendants' CIP based on use of an inorganic polymer support were new material not encompassed by their parent application … they therefore were and are invalid as having been filed more than one year after they were described in the 1980 article" — and map that reasoning onto '319's identical "inorganic polymer" genus language. Full text: CourtListener opinion 2526031. Flag clearly to the court that this holding addressed '066 and '418, not '319; it is persuasive authority, not a judgment against this patent.
• Do not overclaim the inequitable conduct point. The 2004 opinion denied summary judgment on inequitable conduct and set the issue for a 2004-03-04 hearing. I do not have a confident record of the ultimate disposition of that claim (I could not verify a later ruling or the trial outcome). If you intend to plead unenforceability, retrieve the post-2004 docket and the S.D.N.Y. judgment before filing.
• How to confirm the negative yourself: query PTAB E2E / PTACTS (ptacts.uspto.gov) and the PTAB decisions search (developer.uspto.gov PTAB API) by patent number 5153319 and by the "319" string with an assignee filter for University Patents/Competitive Technologies. That filters out the four same-suffix imposters listed above.
• Trial-stage milestones: none. There is no pending proceeding, so there is no institution deadline, no oral hearing, and no § 316(a)(11) one-year FWD clock running against this patent.

Confidence note: I am highly confident in the "no AIA trial proceedings" finding (structured ODP data + independent docket searching agree). I am not asserting that no other post-issuance challenge ever existed — I did not verify whether UPI ever faced a pre-AIA ex parte reexamination on '319, and I have no reliable record either way. If that matters, pull the '319 file wrapper from USPTO Patent Center directly.

I'll research this patent's assignment chain before writing anything. Let me start with targeted searches.

The first searches returned bibliographic data but no assignment records. Let me dig into the ownership history and litigation.

Good — I found litigation context (Millipore v. University Patents). Now let me hunt for the actual recorded assignments and UPI's corporate fate.

Ownership & Assignment Analysis — US 5,153,319

Important methodology caveat up front. I was unable to retrieve a single reel/frame record for this patent. I could not query the USPTO Assignment Center / Patent Assignment Search index directly within my working limits, and every indexed source I did reach (Google Patents legal-events table, Espacenet, Justia/patent aggregators) returned zero recorded assignment entries for US 5,153,319. I will therefore not print reel/frame numbers, correspondents, or execution dates I could not verify. What follows separates (a) what the authoritative patent text and retrievable records show, from (b) what is unverified. Where the format below asks for reel/frame data that does not exist in my sources, I say so rather than filling the slot.

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Inventors

Unusual pattern — flag it: the patent carries a government-interest statement — "The inventions described herein were made in the course of work under a grant or award from the Department of Health, Education and Welfare" — yet the assignee of record is not the University of Colorado. It is a private third-party licensing company, University Patents, Inc. So federally funded, university-lab work was assigned to an outside commercial patent-holding entity. That is the single most consequential ownership fact on this document, and it is the root of the non-practicing posture of the entire chain. I found no evidence of inventors departing a corporate assignee within 12 months — there was no corporate employer to depart from.

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Original assignee

University Patents, Inc. ("UPI") — named as Original and Current Assignee on the Google Patents record.

• Product shipped? No. UPI was a patent licensing/holding company, not an operating concern. It did not manufacture DNA synthesizers or reagents. The operating company in the story was Applied Biosystems, Inc. ("ABI" / "ABIO"), which held an exclusive license and sold the instruments and reagents — ABI appears as licensee, not as assignee.
• Primary line of business: acquiring rights in university-originated patents and licensing/asserting them — the 1970s–80s archetype of the modern NPE. (UPI's litigation over patents it licensed in from universities is documented, e.g. the University Patents, Inc. v. Kligman line of cases in D. Del., which I list here as context on UPI's business model, not as a record tied to 5153319.)
• Current status: Not verified. I could not confirm whether UPI is still operating, was wound down, renamed, or sold its portfolio. I will not guess. Two concrete observations from the record: (i) Google Patents still returns UPI as Current Assignee, i.e. no downstream reassignment is indexed; and (ii) the patent's legal status is Expired – Fee Related, with an anticipated expiration of 2009-10-06, meaning it lapsed rather than being maintained to full term.

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Assignment timeline

No recorded assignment is retrievable for US 5,153,319 from the sources available to me.

Specifically:

• The Google Patents Legal Events table for US5153319A lists exactly five entries — the 1986-03-31 filing and priority claim by University Patents Inc, the 1992-10-06 grant, the 1992-10-06 publication, and the 2009-10-06 anticipated expiration. No "Assignment" event appears.
• The "Current Assignee" field is still populated as University Patents Inc, consistent with no indexed change of title.

I cannot state that "the Assignment Center has no records" — that would be asserting a negative I did not personally check at the registry. The accurate statement is: no post-issuance assignment of title is reflected in any index I could reach, and the assignee of record appears never to have changed. Anyone needing a definitive answer should query https://assignmentcenter.uspto.gov/ by patent number 5,153,319 and confirm reel/frame directly.

Because there is no assignment chain, there are no correspondent-of-record entries to capture, and no recurrence analysis of a recording attorney is possible for this patent. That absence is itself material: the classic NPE tell — a repeat recording attorney running a chain of look-alike LLCs — is simply not observable here, because there is no chain.

What did happen to this patent was licensing and litigation, not assignment, documented as follows:

• ~1986–1988 — UPI, with exclusive licensee ABI, ran an enforcement/licensing campaign across the polynucleotide-synthesis family. Per Millipore Corp. v. University Patents, Inc., 682 F. Supp. 227 (D. Del. 1988), UPI had letters sent "throughout the industry threatening suit to those who infringed UPI's patents," and pending California litigation against another party ("GMBH"). ABI's James Kitch offered Millipore a sublicense on a "take-it-or-leave-it" basis, with litigation as the alternative. This is licensing pressure backed by the patent title, not a transfer.
• 1991-10-01 — Sublicense Agreement between Applied Biosystems, Inc. and Cruachem Holdings, Ltd., covering "certain U.S. and foreign patents related to polynucleotide synthesis, originally assigned to University Patents, Inc.," executed as part of settling prior litigation (document indexed at contracts.justia.com). Confirms UPI remained the title holder while ABI sublicensed.
• 2009-10-06 — Patent expires/lapses on fee grounds. The Google Patents banner "Family has litigation" links to a Darts-IP family record (family=25297985).

Flag — a records discrepancy worth chasing: the patent text states "This is a continuation of application Ser. No. 601,813 filed Jun. 18, 1984, now U.S. Pat. No. 4,458,066." Espacenet indexes US 4,458,066 as filed 1980-02-29 and issued 1984-07-03. A continuation filed 1984-06-18 cannot issue 15 days later as the same patent. The dates as printed/fetched are mutually inconsistent; the priority chain for the Caruthers family (4,458,066, 5,132,418, 5,153,319) should be verified against the actual file wrappers before anyone relies on it for term or priority.

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Timeline diagram

timeline
    title Ownership of US 5153319
    1980 : Earliest Caruthers family filing
    1980 : Rights held by University Patents Inc
    1986 : US 5153319 application filed 31 March
    1987 : UPI and ABI press industry for licenses
    1988 : Millipore challenge rejected by D Del
    1991 : ABI sublicense granted to Cruachem
    1992 : US 5153319 granted 6 October
    2009 : Patent lapses for unpaid fees

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NPE / troll-pattern signals

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Verdict

Insufficient data.

Justification: there is no retrievable recorded assignment chain for US 5,153,319 — Google Patents legal events show only filing, priority, grant, publication and anticipated expiration, and the Current Assignee field still reads University Patents Inc — so four of the eight signals (1, 3, 4, 5) cannot be assessed and the "known asserter" and "defensive aggregator" tests come back negative. The substantive evidence is a licensing/enforcement history rather than an ownership history: UPI and its exclusive licensee Applied Biosystems threatened the industry with suit in 1987–88 per Millipore Corp. v. University Patents, Inc., 682 F. Supp. 227 (D. Del. 1988), and ABI sublicensed Cruachem on 1991-10-01 under patents "originally assigned to University Patents, Inc." That is a non-practicing assertion posture from day one — but it is documented as licensing, not as an assignment chain, and I have no reel/frame, no correspondent, and no verified current owner, so I cannot grade this as NPE-moderate without fabricating the missing links. For completeness: the patent is expired (2009-10-06, fee-related) and the asserted family members were the earlier filings, so no live assertion risk attaches to this number today.

Verify at: https://assignmentcenter.uspto.gov/ — search patent number 5153319; and cross-check https://patents.google.com/patent/US5153319/en (Legal Events tab) plus the Darts-IP family-litigation record https://patents.darts-ip.com/?family=25297985. If the Assignment Center returns hits, the reel/frame numbers and correspondent names there should be treated as authoritative over everything above.

I'll research US 5,153,319 and its cited prior art. Let me run targeted searches.

Let me pull the actual front-page citations for US 5,153,319.

Let me try to retrieve the front-page citation list directly.

Scope and method — read first

I could not complete an authoritative USPTO‑database query in this session. My tool is a general web search, and the front‑page "(56) References Cited" module for US 5,153,319 did not render in the authoritative text I was given (that text runs from title → abstract → description and is truncated mid‑description, with no (56) block and no claim text). Accordingly, below I separate:

• (A) citations that are verifiable from the authoritative US 5,153,319 text itself (the specification's own references),
• (B) the Caruthers/University Patents family members and litigation‑identified patents surfaced by search,
• (C) forward citations (patents citing 5,153,319) — included because "patent citation for 5153319" is direction‑ambiguous, but flagged as not prior art,
• flagged items are things I could not verify and will not fabricate.

A verification query you should run to close the gap: USPTO Patent Public Search / PatentCenter for application 06/846,453 (the granted‑patent file wrapper will list the examiner‑cited references), and the Google Patents "Patent citations / Non‑patent citations" module at https://patents.google.com/patent/US5153319/en.

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1. Identification of the subject patent (verified from the authoritative text)

Continuity statement as literally rendered in the text: "This is a continuation of application Ser. No. 601,813 filed Jun. 18, 1984, now U.S. Pat. No. 4,458,066."

⚠️ Flagged discrepancy (reported, not corrected): this literal statement is chronologically impossible as written — US 4,458,066 is recorded elsewhere as filed 1981‑03‑24 and issued 1984‑07‑03 (LexDana, https://lexdana.ai/patent/4458066), i.e. it issued nine days after Ser. No. 601,813 was filed, and Ser. No. 601,813 appears to correspond to US 5,132,418 (filed 1984‑06‑18, Caruthers & Matteucci, University Patents Inc.; https://idiyas.com/patent/badge/[5132418](/patent/5132418)). This is most likely a truncation/OCR artifact at the source, but per your rule I am not auto‑correcting it — verify the continuity chain against the printed patent and PatentCenter.

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2. References cited in the specification of US 5,153,319 (Group A)

These are the only references I can tie to the US 5,153,319 disclosure with primary‑source confidence, because they appear verbatim in the authoritative text.

A‑1. U.S. Pat. Nos. 3,419,517; 3,519,538; 3,652,761; 3,669,841

• Full citation (as given in the patent): "methods described in U.S. Pat. Nos. 3,519,538; 3,419,517; 3,652,761; and 3,669,841."
• Dates: none stated in the patent. All are numerically in the 3.4–3.7M series, i.e. pre‑1972 issuance with 1960s filing dates. (I did not retrieve their issuing/filing dates or titles in this session — treat as unverified.)
• Brief description (as characterized by the patent itself): these are cited for "the production of a variety of functional groups on the surface of the silica gel suitable for reaction with the hydroxy (3'‑ or 5'‑) of the initial nucleoside." In the art at that time, the 3,4xx,xxx/3,5xx,xxx/3,6xx,xxx − 538/−761/−841 cluster is the immobilized‑biologically‑active‑material literature on siliceous supports derivatized with organosilanes (e.g., γ‑aminopropyltriethoxysilane) to install amino/hydroxy functionality (moderate confidence — I did not confirm titles; do not rely on this characterization without checking).
• § 102 potential: All predate the earliest plausible priority (1980‑02‑29, per the sibling US 4,458,066) and the 1986‑03‑31 filing by far → they are § 102(b) printed‑publication/patent art. They could, in principle, anticipate a claim drawn only to an amino‑ or hydroxy‑functionalized inorganic support. They cannot anticipate any claim of US 5,153,319 as issued, because every claim family I can identify requires the support to carry a nucleoside covalently bound through a dicarboxylic‑acid‑derived (succinyl/ester/amide) linkage (claims 1–17), or requires the polymer‑bound nucleoside in a phosphite condensation (claims 18–43). These four patents disclose support functionalization only → best characterized as § 103 combination art for the "derivatize the silica" steps, not § 102 anticipation.

A‑2. H. Köster, Tetrahedron Letters, 1972, pp. 1527–1530

• Full citation: H. Köster, Tetrahedron Letters, 1527–1530 (1972). (The patent is the sole source for the page range; no volume/issue is stated.)
• Date: 1972 → § 102(b) art.
• Brief description (per the patent): "The attachment of nucleosidephosphates to silica gel using a trityl linking group … but the method is apparently applicable only to pyrimidine nucleosides. The cleavage of the nucleoside from the silica support can only be accomplished with acid to which the purine nucleosides are sensitive."
• § 102 potential — this is the single most relevant backward citation: it is the closest art on a nucleoside covalently attached to a silica gel support. Anticipation risk is nonetheless low, because:
  • its linkage is a trityl (acid‑labile) linkage, whereas claim 1/claim 7 require the linkage to be through an ester linkage formed via a dicarboxylic acid (e.g., succinyl) with the sequence (silica gel)–(CH2)n–NHCO–Z–CO– (n = 1–5; Z = divalent hydrocarbyl ≤ C10) — see the text's formula and the succinic‑anhydride/aminopropylsilane chemistry in Examples 1, 2 and 6;
  • it is limited topyrimidine nucleosides, whereas claims 12 and Examples 5–6 expressly cover purine bases (adenine, guanine);
  • claim 7/13 require the 3'‑O ester attachment with a 5'‑O blocking group, and claims 30/31 require Lewis‑acid (ZnBr₂) detritylation — Köster teaches the opposite (acid cleavage, purine‑incompatible).
  • Verdict: § 103 art of record importance; does not anticipate claims 1–43. If the examiner treated it as anticipatory, it could only be against a hypothetical generic "nucleoside‑on‑silica" claim, which is not in this claim set.

A‑3. R. L. Letsinger and W. B. Lunsford, J. Am. Chem. Soc., 98(12), 3655–3661 (1976)

• Full citation as given: "R. L. Letsinger and W. B. Lunsford, Journal of the American Chemical Society, 98:12, 3655‑3661."
• Date: 1976 → § 102(b) art.
• Brief description (per the patent): "The production of phosphotriester derivatives of oligothymidylates … by reaction of a phosphorodichloridite with a 5'‑O blocked thymidine and subsequent reaction of the product with a 3'‑O‑blocked thymidine followed by oxidation of the resulting phosphite to a phosphate and removal of blocking groups … using this procedure, the tetramer and pentamer products dTpTpTpT and dTpTpTpTpT were prepared." The patent criticizes it because "the process requires separation and purification of products at each stage."
• § 102 potential: Letsinger/Lunsford discloses the activated phosphite triester coupling/oxidation/deblocking cycle — the same core chemistry recited in claim 18 ("condensing the 3'‑OH or 5'‑OH group of a nucleoside or oligonucleotide … to the phosphite compound"), claims 34–42, and the oxidation steps of claims 26/27 (I₂) and 35/36. However, it is solution‑phase: it contains no inorganic‑polymer support, no silica gel, no succinyl/ester anchor, no capping of unreacted support‑bound 5'‑OH, and no Lewis‑acid detritylation. Because claim 18 and claim 34 both expressly require the nucleoside/oligonucleotide to be bound to the functionalized inorganic polymer support, and claim 34 requires the phosphite reactant to bear the specified –P(R₁)(X) group for coupling to that bound species, Letsinger/Lunsford does not anticipate any claim. → § 103 art only; the classic "phosphite chemistry was already known" reference.

A‑4. V. Amarnath and A. D. Broom, Chemical Reviews 77, 183–217 (1977)

• Full citation as given: "V. Amarnath and A. D. Broom, Chemical Reviews 77, 183‑217 (1977)."
• Date: 1977 → § 102(b) art.
• Brief description: cited as the review of polymer‑supported polynucleotide synthesis, relied on for the statement of the problems the invention solves: "(1) slow diffusion rates of activated nucleotides into the support; (2) excessive swelling of various macroporous, low cross‑linked support polymers; and (3) irreversible absorption of reagents onto the polymer."
• § 102 potential: a general review — no anticipation of any of claims 1–43 (it does not disclose the silica‑gel/ester/succinyl support, the phosphite‑on‑support cycle, or ZnBr₂ detritylation). Its only significance is as § 103 background establishing that organic polymer supports were known and their drawbacks recognized → i.e., motivation to switch to inorganic supports.

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3. Family / related‑patent citations (Group B)

These are the "citations" you most likely want if you mean the Caruthers patent family. All share the same inventive entity (Caruthers and/or Matteucci) and the same assignee (University Patents Inc.), so they are not "by others" and cannot be pre‑AIA § 102(a), (b), (e), (f) or (g) prior art against US 5,153,319. Their real exposure is obviousness‑type double patenting / terminal disclaimer, not § 102.

⚠️ Note the date conflict for US 4,458,066: one secondary source gives "issued 1984‑07‑03, filed 1981‑03‑24" (LexDana) while justia's citation tables list "4458066 | July 3, 1984" (consistent). I found no source supporting a 1984‑03‑07 date; disregard if you see that variant elsewhere. Dates for 4,415,732; 4,500,707; 4,668,777; 4,973,679 above come from justia citation tables (publication dates only; filing dates not verified).

§ 102 analysis for Group B: No § 102 anticipation by any family member. US 4,458,066 and US 5,132,418 disclose the same subject matter as 5,153,319 (they are in the same continuity chain and, for 4,458,066, are effectively the same disclosure), but a patent or application naming the same inventive entity is not prior art under § 102(a)/(b)/(e) against that entity's later patent. Because US 4,458,066 and US 5,132,418 both have earlier effective filing/issue dates than 5,153,319, the examiner's concern would properly be statutory‑type or obviousness‑type double patenting, addressed by a terminal disclaimer.

Litigation context (not prior art): The Google Patents record carries an active "Family has litigation" flag; public reporting states PEB (Perkin‑Elmer/PE Biosystems) sued Affymetrix in D. Del. asserting US 4,458,066, 4,500,707, 5,132,418, 5,153,319 and 4,973,679 (https://www.biocentury.com/article/[189833](/patent/189833)/affymetrix-pe-biosystems-enabling-technology-news). If you are looking for invalidity art actually litigated, that docket (and the corresponding IPR/reexam file histories) is where the § 102/§ 103 challenges to 5,153,319 will be pleaded.

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4. Forward citations (patents citing 5,153,319) — not prior art, listed only for completeness

5,153,319 is cited as background/incorporated‑by‑reference in a large number of later filings, e.g. EP 1710562 A2 ("US 4458066 A; US 4500707 A; US 5153319 A [0060]"), EP 2101823 B1 / DK 2101823 T3, EP 1176151 B1, EP 3825400 B1, EP 4008783 A1, EP 3527224 B1 (RNA‑analog preparation), US 9,701,965, US 10,815,291, US 9,631,182, WO 2011/091534 A1, and the CureVac‑style lists ("US 4373071, 4401796, 4415732, 4458066, 4500707, 4668777, 4973679, 5047524, 5132418, 5153319, 5262530, 5700642"). These are later‑published documents and therefore cannot anticipate US 5,153,319; they matter only for reading the family's commercial/technical footprint.

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5. Bottom‑line § 102 table

Net conclusion: the two references with genuine substantive bite against US 5,153,319 are Köster 1972 (nucleoside‑silica attachment, but wrong linkage/bases) and Letsinger & Lunsford 1976 (the phosphite‑triester coupling cycle, but solution‑phase with no support); Amarnath & Broom 1977 supplies the "why inorganic supports" motivation, and the four 3,4xx,xxx–3,6xx,xxx U.S. patents supply the silane/silica functionalization. On the record I can verify, none of them anticipates the specific combination recited in the claims — the dicarboxylic‑acid ester anchor through the 3'‑O (claims 7, 13, 17), the 25–1000 µm macroporous silica support with blocked silanols (claims 3, 4, 6, 9, 15, 23), the 10–30‑mer chain limit (claims 33, 40), the Lewis‑acid/ZnBr₂ detritylation of a 5'‑O‑dimethoxytrityl group (claims 30, 31), and hydrolysis of the ester to liberate the oligonucleotide (claim 41). The realistic attack is a § 103 combination (Köster or the Messing‑type silane patents + Letsinger/Lunsford + Amarnath/Broom), not § 102.

Claim numbering caveat: the claim set I quoted (1–17 compositions; 18–33 process via polymer‑bound nucleoside; 34–42 process via phosphite compound; 43 process for polynucleotides) comes from a secondary rendering of the sibling patent US 4,458,066 (LexDana), not from the truncated US 5,153,319 text supplied to me. Both patents share title, inventors, assignee and specification; verify the exact numbers against the printed US 5,153,319 claims before relying on any specific claim number in a filing or opinion.

What I could not verify (no fabrication): the exact front‑page (56) list for US 5,153,319; the examiner of record and any examiner‑cited art for application 06/846,453; and the bibliographic details (titles, issue/filing dates, inventors, assignees) of US 3,419,517, 3,519,538, 3,652,761 and 3,669,841. A USPTO PatentCenter pull on 06/846,453 and a full‑text lookup of those four numbers will close those gaps.

I'll ground this analysis in the patent's own prior-art citations and the actual claim scope. Let me pull the claim text and the cited references.

Let me pin down the actual claim scope of '319 and the identity of the 1980 Caruthers article that the litigation record treats as dispositive prior art.

Obviousness Analysis — U.S. Patent 5,153,319 (Caruthers & Matteucci, "Process for Preparing Polynucleotides")

0. Scope note before we start (important for reliability)

Two things you should weigh before relying on this:

1. The claim text was not in the material shipped with the patent page. The Google Patents text you gave me contains the definitions/description/abstract, but the "Claims" section itself was not reproduced. I therefore pulled the claim set from a third-party record (RPX/insight): claims 1–7, 11 and 14 of the stated 17 claims are visible there, with OCR artifacts (e.g., claim 1 says "oligonnucleotides"; the "[3]" and "[5]" formula blocks are garbled). Quotes below are transcribed as found, uncorrected, per your instruction.
2. Your two date sources disagree: the system prompt says 26 April 2026; the fetched page says it was retrieved 2026‑09‑30. I treat the patent text and record as authoritative and the dates as metadata only.

Also, per your literal-interpretation rule, I am flagging rather than correcting an internal inconsistency in the patent itself: US5153319's specification states "This is a continuation of application Ser. No. 601,813 filed Jun. 18, 1984, now U.S. Pat. No. 4,458,066." The litigation record states that the June 18, 1984 application is the one that issued as US 5,132,418 on July 21, 1992, and that US 4,458,066 is associated with a March 24, 1981 filing (parent filed Feb 29, 1980). I do not resolve this; it matters for the critical date, so I analyze under both the 1986‑03‑31 filing/priority date and the possible 1984‑06‑18 benefit date.

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1. Legal framework and the critical date

35 U.S.C. § 103, pre‑AIA (which governs, since the application was filed 1986‑03‑31):

• Graham v. John Deere Co., 383 U.S. 1 (1966) factors: scope/content of the prior art; differences between the prior art and the claims; level of ordinary skill; objective indicia.
• KSR Int'l v. Teleflex, 550 U.S. 398 (2007): combination of familiar elements according to known methods, yielding predictable results, is obvious; a "finite number of identified, predictable solutions" supports obviousness.

Critical date assumptions:

Either way, US 4,458,066 is prior art against '319 — it is more than one year before both candidate filing dates. Same-inventor identity does not remove it from §102(b), and pre‑AIA §103(c) (common ownership) postdates this application and is unavailable. This is the single most important structural fact in the analysis: '319 is a later continuation whose claims are drawn to support-functionalization methodology that its own patent family already published.

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2. Level of ordinary skill in the art (step 3)

A person of ordinary skill as of 1984–1986 would be a chemist/biochemist (Ph.D., or M.S. with several years' hands-on experience) working in nucleic acid chemistry, familiar with:

• Merrifield-style solid-phase synthesis;
• the phosphite triester approach of Letsinger (JACS 1976, 98(12):3655–3661);
• silane derivatization of silica and carbodiimide-mediated coupling — including the aminosilane/succinylation/linkage toolkit taught by the inorganic-support patents the patent itself cites (US 3,519,538; 3,419,517; 3,652,761; 3,669,841);
• trityl/dimethoxytrityl protection and its acid-lability, and purine depurination under protic acid.

This is a highly skilled, small, well-informed art. That cuts toward obviousness for incremental support-chemistry claims.

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3. The claims at issue (as retrievable)

Note the scope asymmetry. Claims 1–13 are support-preparation claims — they stop at a derivatized, nucleoside-loaded silica. Claim 14 is the coupling-chemistry claim and is essentially '066 claim 18 with X narrowed to the heterocyclic‑amino species. The '319 patent's own specification reproduces the '066 disclosure essentially verbatim.

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4. Ground-by-ground obviousness analysis

Ground I — Claims 1–13 over US 4,458,066 alone, or in view of Köster 1972

US 4,458,066 (issued 1984‑07‑03) claims, inter alia, a modified inorganic polymer linked to the 3′‑ or 5′‑O through a base-hydrolyzable covalent bond; claim 7 an inorganic polymer linked through an ester linkage at the 3′‑O; claim 13 an oligonucleotide bound through an ester linkage formed through the 3′‑OH of the initial nucleoside; and claim 43 "a process for producing polynucleotides which comprises the step of condensing the 3′‑OH or 5′‑OH of a nucleoside linked to a functionalized inorganic polymer with a compound which is the reaction product of nucleoside and blocked phosphodichloridite." Its Example 1 gives the whole support-prep recipe: 3‑aminopropyltriethoxysilane reflux in toluene → succinic anhydride (pH 4–6) → trimethylsilyl chloride capping → carbodiimide coupling of 5′‑O‑dimethoxytrityldeoxythymidine → deblocking, with ~40 µmole/g loading.

That is claims 1, 3, 4, 6, 7 and 11 of '319 element-for-element, including the aminoalkylsilane → half-ester-of-dicarboxylic-acid → carboxy/hydroxy condensation sequence. Independently, the 1980 Tetrahedron Letters report by the same inventors was found by the EPO to destroy the novelty of claims 1–24, 27, 29 and 30 of the '066 application (CourtListener, Affymetrix v. PE Corp.). Claims in that numeric range include the process claims. If those EPO-identified claims read on the 1980 publication, the closely parallel '319 support-prep claims are at minimum obvious — and, on the EPO's reasoning, arguably anticipated.

Why the ordinary artisan would combine: no combination is needed for Ground I. Where '066 is treated as the closest art, Köster (Tetrahedron Letters 1527–1530, 1972) supplies the silica/trityl/nucleoside anchor and expressly frames the problem the claims solve ("apparently only applicable to pyrimidine nucleosides"; cleavage "only … with acid to which the purine nucleosides are sensitive"). Swapping an acid-labile trityl anchor for a base-labile ester/amide anchor to tolerate purines is a predictable, mechanism-known substitution, not an invention.

Ground II — Claims 1–13 over Köster + Letsinger & Lunsford + Amarnath & Broom + the silica-functionalization patents

• Köster, Tetrahedron Letters 1527–1530 (1972) — nucleoside phosphates attached to silica gel via a trityl linking group; establishes silica's utility as a support and its deficiencies.
• Letsinger, R. L. & Lunsford, W. B., JACS 98(12):3655–3661 (1976) — "Synthesis of thymidine oligonucleotides by phosphite triester intermediates"; dichloridite + 5′‑O‑blocked thymidine, then 3′‑O‑blocked thymidine, then oxidation to phosphate; prepared dTpTpTpT and dTpTpTpTpT, but required separation and purification at each stage.
• Amarnath & Broom, Chem. Rev. 77, 183–217 (1977) — the patent's own cited review documenting the failure modes of organic polymer supports: slow diffusion of activated nucleotides, excessive swelling, irreversible reagent adsorption.
• US 3,519,538; 3,419,517; 3,652,761; 3,669,841 — explicitly incorporated by the '319 specification as "known methods" for putting functional groups on silica for reaction with the 3′‑ or 5′‑hydroxy of the initial nucleoside.

Motivation to combine (why this is a textbook KSR combination):

1. Amarnath & Broom supplies a recognized, documented problem with organic supports (diffusion, swelling, adsorption). Köster supplies a known candidate solution: an inorganic (silica) matrix, which the '319 specification itself says "avoid[s] swelling" and "resist[s] adsorption."
2. Letsinger supplies the phosphite triester coupling chemistry and the known price of not using a support — a purification at every chain extension. Converting a solution-phase, purify-every-step synthesis to a solid-phase format was the central, well-motivated objective of the field.
3. The silica-functionalization patents supply the linker (aminoalkylsilyl → dicarboxy half-ester) and the standard coupling reagent for the carboxy/hydroxy condensation. Nothing more than routine adaptation.
4. Köster's own admitted limitation (pyrimidine-only; acid cleavage) supplies the reason to select a base-cleavable ester/amide linkage over the trityl anchor — a finite, identified, predictable set of options (§103 "finite number of identified, predictable solutions," KSR).

The '319 specification's own "Definitions" section is effectively an applicant-admitted prior art statement that guts the novelty of the individual steps: "Hydroxy and amino functionality where not present on the inorganic support can be introduced by known methods"; "the nature of the reactive group which bonds the nucleoside to the polymer support is not critical"; "the structure of the covalent linkage … is not critical as long as a substantially stable covalent linkage is formed."

Ground III — Claim 14 over '066/'418/'707 in view of Beaucage & Caruthers (1981) and Matteucci & Caruthers (1981)

Claim 14's only real narrowing versus '066 claim 18 is that X is a heterocyclic-amino leaving group (tetrazolyl, imidazolyl, nitroimidazolyl, triazolyl, etc.) rather than Cl/Br or a secondary amino group.

Prior art supply:

• '066 claim 18 already covers "X is Cl or Br, or a secondary amino group," and the '319 specification itself defines that secondary amino group as "formed by removal of the hydrogen atom from a ring nitrogen of a nitrogen containing heterocyclic compound which contains unsaturated bonds in the ring structure" — i.e., the species of claim 14 is defined in the '066-family disclosure.
• US 4,500,707 ("Nucleosides useful in the preparation of polynucleotides," issued 1985‑02‑19) and US 4,973,679 disclose nucleoside phosphite/phosphoramidite species with trityl blocking groups and silica gel supports, including the nitrogen-heterocycle-activated variants and the better-known art of Beaucage & Caruthers, Tetrahedron Lett. 22:1859–1862 (1981) (the phosphoramidite method) and Matteucci & Caruthers, JACS 103:3185–3191 (1981) (confirmed in the family citation practice of later patents).

Motivation: the field knew that chloridites are moisture/air sensitive and awkward to handle, and that activating a nucleoside phosphite with a weak acid such as tetrazole gives faster, cleaner coupling with higher yields. Selecting an unsaturated nitrogen heterocycle (tetrazole being the paradigmatic weak-acid activator) as the leaving/activating group is the predictable use of a known activator for its known property — the very definition of In re Kerkhoven-style / KSR obviousness. Claim 14 adds no structural or functional surprise.

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5. Differences between the prior art and the claims (step 2) — what actually helps the patentee

Realistically, the patentee's only non-trivial differentiators are:

• Base-hydrolyzable ester/amide linkage on an inorganic support as the combination — but this is squarely what '066 (and the 1980 TL publication) disclosed, so it cannot differentiate '319 from its own family art.
• The 2–3 hour cycle time with ≥95% per-addition yield and yields maintained as the chain grows (spec: "Each mononucleotide addition requires maximally 2-3 hours with yields of 95% and greater"; isolated yields of d(T)₉ ≈ 25% and the nonamer d(T‑C‑T‑C‑T‑C‑T‑T‑T) ≈ 23%). This is a result, and results that are the natural consequence of a known solid-phase format are rarely enough to rescue obviousness absent unexpected magnitude.
• Full automation (the valve/reservoir/UV-detector scheme of the drawing and Table I). Note this is described in the specification but I did not see it recited in any of the claims I could retrieve; if it is claimed, it should be evaluated separately, and it too is a mechanical combination of known laboratory-automation elements.
• The ZnBr₂/Lewis-acid detritylation that avoids depurination (spec: "reaction is extremely fast and is not accompanied by depurination"). This is a genuine, articulable technical advance over protic-acid detritylation. However — check whether it is claimed. On the claim text I could retrieve, it is not; it appears only in the written description. Unclaimed subject matter cannot confer patentability.

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6. Objective indicia (step 4) — the patentee's best rebuttal, with a nexus problem

Two things in the record genuinely favor non-obviousness:

1. Long-felt need / failure of others. Amarnath & Broom (1977) documents years of inadequate polymer supports; Letsinger's solution-phase method required purification at every step. This is the classic "failure of others" narrative.
2. Commercial success. As described in the literature: by the late 1980s the phosphoramidite/solid-phase method "became the industry standard for oligonucleotide synthesis and ABI had virtually a monopoly within this market due to the exclusive license to Caruther's patents," and the synthesis cycle "has remained relatively unchanged for three decades."

The nexus problem is severe. The commercial success is attributable to the integrated solid-phase phosphoramidite system and to ABI's instruments — which trace to '066, '418, '432 and the automated-synthesizer art — not specifically to the support-preparation steps recited in '319 claims 1–13. Where the claim covers only "convert silica to aminosilica and attach a half-ester of a nucleoside," the success evidence is not commensurate with the claim scope. Expect the examiner/court to discount it.

Countervailing objective evidence against the patent: the Affymetrix v. PE Corp. record indicates UPI failed to disclose the 1980 article to the examiner for either application; the court's narrative states the article was "an absolute bar to any claims disclosed in the article," that it "meets every material element and limitation of [the interference count]," and that UPI disclosed it only sporadically thereafter. That is a candor/inequitable-conduct overlay, and a hint that the '319 claims would not likely survive a clean §103 challenge.

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7. Bottom line

Stated as a formal rejection: Claims 1–13 would be rejected under pre‑AIA 35 U.S.C. § 103(a) as obvious over Caruthers & Matteucci, US 4,458,066 (and the inventors' own February 1980 Tetrahedron Letters report), in view of Köster, Tetrahedron Letters 1527–1530 (1972); Letsinger & Lunsford, JACS 98(12):3655–3661 (1976); Amarnath & Broom, Chem. Rev. 77:183–217 (1977); and US 3,519,538, 3,419,517, 3,652,761 and 3,669,841. Claim 14 would be rejected under § 103(a) over '066 claim 18 in further view of Beaucage & Caruthers (1981) and Matteucci & Caruthers (1981). The motivations are (i) the admitted swelling/diffusion/adsorption failures of organic supports, (ii) the admitted acid-lability and pyrimidine-only limitation of the Köster trityl-silica system, (iii) the admitted need to avoid purification at every chain-extension step, and (iv) the express incorporation by reference of the silica-functionalization patents.

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8. What I could not establish (please do not treat these as settled)

• The complete, official claim set (all 17 claims). My claim text is from a secondary aggregator with OCR damage; claims 8–10, 12, 13, 15–17 are not in my hands. Claim 11's text is visibly incomplete, and claim 1's "oligonnucleotide" spelling may be an OCR artifact rather than the issued text.
• The exact bibliographic citation of "the 1980 article." The litigation record dates it to "Tetrahedron Letters, February 1980" (hence volume 21), but I could not confirm title and page numbers with high confidence, and I will not guess them.
• Whether the issued '319 claims include the automation, capping, or ZnBr₂ features described in the specification. This materially changes the analysis, and it should be verified against the granted claim set.
• The priority chain. The '319 specification's "continuation of Ser. No. 601,813 … now U.S. Pat. No. 4,458,066" statement conflicts with the litigation record; I flagged rather than corrected it, as instructed.
• The Google Patents "Prior Art" reference table was not part of the material supplied; my art list is reconstructed from the specification's Background section, the claim citations in the family, and the litigation record.

Sources used: US5153319 on Google Patents · claim text (RPX insight) · Affymetrix, Inc. v. PE Corp. (CourtListener) · US 4,458,066 bibliographic data (Espacenet) · principal claims of US 4,415,732 and 4,458,066, Biotechnology Law Report 4:259 (1985) · Letsinger & Lunsford, JACS 98(12):3655–3661 (1976) · Köster, Tetrahedron Letters 1527–1530 (1972), as quoted in JPH0327395A