Invalidity dossier
US 7049102
Multi-gene expression profile
Current assignee: Leland Stanford Junior University
Added 9/27/2026, 6:26:16 PM
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Patent summary
Title, assignee, inventors, filing/issue dates, abstract, and a plain-language overview of the claims.
I'll search for information on this patent number, including any CAFC litigation activity.
Let me try to retrieve the literal claim text, which wasn't included in the authoritative text provided.
US 7,049,102 B1 — Summary
Caveat on sources: I could not retrieve the USPTO full-text claim set or any CAFC docket entry for this patent through search. The summaries below are grounded in the authoritative patent text supplied to me plus Google Patents/Justia bibliographic data. Exact claim wording/numbering is not verified — see the uncertainty note at the end.
Bibliographic data
| Field | Value |
|---|---|
| Patent number | US 7,049,102 B1 (no letter suffix error — "B1") |
| Title | Multi-gene expression profile |
| Application | 09/713,545 |
| Filing date | November 15, 2000 |
| Issue date | May 23, 2006 |
| Earliest priority | September 22, 1989 (via the continuation chain) |
| Inventors | Russell N. Van Gelder; Mark E. Von Zastrow; Jack D. Barchas; James H. Eberwine |
| Assignee | Board of Trustees of the Leland Stanford Junior University (original assignee: Leland Stanford Junior University) |
| Legal status | Expired – Fee Related; anticipated expiration listed as 2009-09-23 |
| Government interest | NIH contract MH23861; NIH confirmatory license recorded 2008 |
Continuity chain (from the spec): This is a continuation of 09/286,533 (filed Apr. 5, 1999 → US 6,291,170), itself a continuation of 08/922,965 (filed Sep. 3, 1997 → US 5,891,636), a continuation of 08/636,748 (filed Apr. 19, 1996 → US 5,716,785), a continuation of 07/957,647 (filed Oct. 5, 1992 → US 5,545,522), which was a continuation of 07/411,370 (filed Sep. 23, 1989, abandoned). Note a minor internal discrepancy: the priority date is listed as 1989-09-22 while the spec states 07/411,370 was filed Sep. 23, 1989. I report both literally.
Classification: C12P19/34; C12Q1/6809 (differential detection); C12Q1/6865 (promoter-based amplification).
Abstract (verbatim)
"This invention relates to the use of promoters for ribonucleic acid amplification and other genetic manipulations. Processes are provided wherein complementary deoxyribonucleic acid (cDNA) is synthesized from a ribonucleic acid (RNA) sequence using a complementary primer linked to an RNA polymerase promoter region complement and then anti-sense RNA (aRNA) is transcribed from the cDNA by introducing an RNA polymerase capable of binding to the promoter region. Additional processes using the resulting aRNA are also described."
Plain-language overview (note on the title)
Despite the title "Multi-gene expression profile," the disclosure is the foundational anti-sense RNA (aRNA) amplification patent (the Eberwine/T7-polymerase method). The specification's stated field is "improved methods for producing amplified heterogeneous populations of RNA from limited quantities of cDNA."
The Summary of the Invention recites four independent process families (which correspond to the independent claims I could not literally retrieve):
Core amplification process — Hybridize a "primer complex" (a primer complementary to the target sequence plus an RNA-polymerase promoter in anti-sense orientation) to a target; extend to make a first cDNA strand, then a second (complementary) strand; then transcribe multiple copies of anti-sense RNA from the second strand using a promoter-specific RNA polymerase. Promoters are preferably prokaryotic/phage (T3, T7, SP6); a preferred T7 primer is SEQ ID NO: 1 / SEQ ID NO: 2. Amplification runs at least ~20–40×, typically 50–100× or 250×, and up to 500–1000× or more, from nanogram-or-less quantities of cDNA.
Gene-expression detection in a preselected cell population — (a) make ds-cDNA from mRNAs of the cell population using a primer linked to a promoter oriented to direct anti-sense transcription; (b) transcribe the cDNA into aRNA with the matching polymerase; (c) determine presence/absence of aRNA complementary to the mRNA of the gene of interest. Cell populations may be single cells up to 100–1,000,000+ cells (brain nuclei, blood cells, neural cells, tumor cells, etc.).
Subtractive hybridization probe production — (a) make a first ds-cDNA collection from a first mRNA population using a primer linked to a first promoter; (b) transcribe aRNA; (c) hybridize that aRNA against a second mRNA population, leaving an unhybridized subpopulation; (d) reverse-transcribe the unhybridized material using a second, different promoter (e.g., T3 or SP6 vs. T7); (e) transcribe a labeled probe. The claimed advantage is that no physical separation of single- vs. double-stranded material is needed.
cDNA library construction — (a) hybridize primer complexes to a plurality of mRNAs; (b) extend to produce ds-cDNAs bearing the promoter; (c) transcribe multiple aRNA copies; (d) prepare a cDNA library from the aRNA copies. This is aimed at libraries from very limited tissue (single cells, single brain nuclei, tissue sections).
A kit embodiment is also described (reverse transcriptase, RNA polymerase, labeled or unlabeled nucleotides, primer complexes, instructions).
Litigation check
- USPTO: The patent is recorded as Expired – Fee Related, with an anticipated expiration of 2009-09-23 (consistent with a 20-year term measured from the 1989 earliest filing date). A 2008 NIH confirmatory license is recorded.
- CAFC 2026 dockets: My search of 2026 Federal Circuit materials returned no case involving US 7,049,102. The 2026 CAFC roundups I retrieved (e.g., Constellation Designs v. LG, Federal Express v. Qualcomm, Enviro Tech v. Safe Foods) are unrelated. This does not prove no such docket exists — a lapse of fee maintenance in 2009 makes current appellate activity unlikely, and my search coverage is not exhaustive.
Uncertainty flags
- Claims text not verified. The authoritative text I was given truncates before the claims, and I could not retrieve the literal claim language via search. The four bullet-point "processes" above are paraphrased from the Summary of the Invention, which likely tracks the independent claims but may not be identical to them (claim count, numbering, and exact antecedent language are unconfirmed). Google Patents' indexed term frequencies (e.g., "gene expression" in ~25 claims, "nucleic acids" in ~45 claims, "cell" in ~27, "RNA polymerase" in ~33) indicate a set of at least 45 claims, but this is an inference from indexing data, not a reading of the claims.
- I did not locate an assignee change of record beyond Stanford→Board of Trustees; the Justia listing also shows the attorney of record as The Luther Law Firm, which I have not independently corroborated.
- The 1989-09-22 vs. 1989-09-23 date discrepancy noted above is reported as-is; I did not auto-correct either value.
Generated 9/27/2026, 6:32:09 PM
Cases on file (0)
Specific litigation cases in our database that name US patent 7049102. The free-form analysis below may also discuss cases beyond this list.
No cases on file mention this patent. Upload a CSV or add a case manually in Admin → Manage litigation cases.
Litigation summary
Past and pending lawsuits — plaintiffs, defendants, jurisdictions, outcomes, and notable rulings.
I'll search for litigation involving US patent 7049102 across patent litigation databases.
The initial results were mostly noise. Let me run targeted searches on litigation-specific databases.
Search Results: Litigation Involving U.S. Patent No. 7,049,102
Bottom line: I found no evidence of any litigation (district court, ITC, PTAB, or Federal Circuit) involving U.S. Patent No. 7,049,102.
Searches performed
I ran targeted queries across patent-litigation-oriented sources, including:
- Google Patents' own litigation/legal-events section for US7049102 (the authoritative page you supplied)
- Unified Patents–style litigation/docket queries (
portal.unifiedpatents.com-oriented searches) - Case-law and PTAB document repositories (CourtListener, Docket Alarm, USPTO PTACTS petition documents)
- Party-name queries (patentee and inventors)
None returned a case docket, complaint, or decision naming U.S. Patent No. 7,049,102 as an asserted patent. The hits returned were false positives arising from unrelated dockets, foreign case numbers, and other patents (e.g., ’102 shorthand in Genzyme v. Fresenius Kabi, D. Del. 1:18-cv-01934, which concerns U.S. Patents 6,987,102 and 7,897,590 — different patents, and a number that must not be conflated with 7,049,102).
What the patent record itself shows (from the Google Patents page you supplied)
- Patent: US 7,049,102 B1, "Multi-gene expression profile"
- Inventors: Russell N. Van Gelder; Mark E. Von Zastrow; Jack D. Barchas; James H. Eberwine
- Assignee: Board of Trustees of the Leland Stanford Junior University
- Application: 09/713,545; filed 2000-11-15
- Granted: 2006-05-23
- Priority: 1989-09-22
- Legal status: Expired – Fee Related; anticipated expiration 2009-09-23
- Government interest: made with NIH support (contract MH23861); a confirmatory license to NIH/DHHS was recorded 2008-11-14
- Family (continuations): US 5,545,522 → 5,716,785 → 5,891,636 → 6,291,170 → 7,049,102
The Google Patents entry for this patent contains no "Litigation" section or court-party data. The absence of a litigation panel on the patent record, combined with a patent that was already expired by 2009, is consistent with there having been no infringement suits asserting this particular patent.
Important caveats — please treat these as limitations, not findings
- Name correction not applied. Consistent with your rule, I interpreted "7049102" literally as US 7,049,102. I did not substitute the more commonly litigated-looking equivalents (e.g., 6,987,102 or 7,049,102's family members). If you intended a different number, the answer may differ.
- Family members not verified for litigation. I did not find (and cannot confirm) any litigation on the sibling patents US 5,545,522, 5,716,785, 5,891,636, or 6,291,170 either. I have no grounded evidence on those, so I make no assertion about them.
- Commercialization / NPE activity unverified. This patent family covers amplified antisense RNA ("aRNA") technology that I understand was later commercially embodied in RNA-amplification products (e.g., the RiboAmp-type kits associated with Arcturus/Applied Biosystems/Thermo Fisher), and the underlying Eberwine technology was the subject of academic and commercial disputes. I could not verify from these searches that any such dispute named US 7,049,102 in a court or agency docket. I flag this only as a lead to check, not as a finding.
- Source access limits. I was not able to retrieve a page directly from the Unified Patents litigation portal or from PACER for this patent. My negative finding rests on the sources above and should be confirmed against PACER/Unified Patents/RPX directly before being relied upon for a legal opinion.
Recommendation
Before relying on a "no litigation" conclusion, confirm directly in:
- PACER / CourtListener RECAP — party-name search ("Stanford" / "Leland Stanford Junior University" plus inventor names Van Gelder, Eberwine, Barchas, Von Zastrow), not just patent-number search
- Unified Patents Litigation portal and RPX/Innography patent-number lookup for 7,049,102
- USPTO PTAB (IPR/PGR/CBM) and assignment/reexamination records for the patent and its family
- USITC EDIS for any Section 337 investigation
If those confirm the negative, the correct answer is: there is no known litigation involving U.S. Patent No. 7,049,102.
Generated 9/27/2026, 6:32:07 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.
I'll start by verifying the structured block against live sources.
Let me run more targeted queries on the patent number and its family.
PTAB / AIA Trial Activity — US 7,049,102 ("Multi-gene expression profile")
Source of record: structured "PTAB proceedings on file" block (USPTO Open Data Portal ingest) supplied with this task.
Verification: independent web searches (Google Patents, Justia, PTAB document servers, PTAB practice literature, Federal Circuit / docket material) surfaced no AIA trial proceeding naming US 7,049,102.
Proceedings overview
Total AIA trial proceedings on file for US 7,049,102: 0 (zero). Breakdown: 0 active, 0 claims invalidated, 0 claims sustained, 0 settled, 0 institution denials. The bottom line is not the usual "hardened patent" story: US 7,049,102 is expired and there has never been a PTAB trial on it — which means there is no IPR pedigree at all, and any demand letter asserting it today is asserting a patent whose term the USPTO record shows as ending 2009-09-23, i.e., roughly sixteen years before the AIA trial regime in its current form matured and before any current sales activity could infringe.
No proceedings to report — explicitly
Per the operating instruction to source the list from the structured block (and to flag only proceedings actually found), I am not inventing proceeding numbers. There is no IPR20xx-xxxxx, no PGR, and no CBM to describe. Accordingly, the per-proceeding template (Type / Filed / Status / Panel / Grounds / Institution / FWD / Settlement / Appeal / Defensive value) is not populated — filling it in would require fabrication.
What I can document from the patent's own front page and the ODP record:
| Item | Value |
|---|---|
| Patent | US 7,049,102 B1 |
| Title | Multi-gene expression profile |
| Inventors | Russell N. Van Gelder; Mark E. Von Zastrow; Jack D. Barchas; James H. Eberwine |
| Assignee | Board of Trustees of Leland Stanford Junior University |
| Appl. No. / Filed | 09/713,545 / 2000-11-15 |
| Granted | 2006-05-23 |
| Priority chain | 09/286,533 → 08/922,965 → 08/636,748 → 07/957,647 → 07/411,370 (filed 1989-09-23, abandoned) |
| Family | US 5,545,522; US 5,716,785; US 5,891,636; US 6,291,170 |
| Anticipated expiration (as listed) | 2009-09-23 |
| Legal status (as listed) | Expired – Fee Related |
| Government interest | NIH contract MH23861 (Stanford subsequently granted the U.S. Government a confirmatory license, recorded 2008-11-14) |
| Source | https://patents.google.com/patent/US7049102/en |
Confidence and caveats (stated plainly):
- High confidence there is no AIA trial on this patent. The canonical ODP block says none, and my searches returned none. The reason is structural, not a reflection of patent strength: the patent's term (as listed) ended in 2009, and IPR/PGR/CBM practice did not exist in any meaningful form until the AIA trial provisions took effect around 2012. A petitioner would have had no forum.
- Moderate confidence on the precise expiration date. "Anticipated expiration 2009-09-23" is Google Patents' assumption, keyed to the 1989-09-23 priority filing (20 years under 35 U.S.C. § 154(a)(2) for a § 120 continuation chain). Patent Term Adjustment could push the date later by some months; the recorded status "Expired – Fee Related" also implies the maintenance-fee trail terminated the patent independently of term. Before relying on expiration in litigation, confirm the operative date on the face of the patent and in USPTO PatentCenter — the "*" terminal-disclaimer asterisk on the printed patent also needs to be accounted for.
- I found no Federal Circuit appeal relating to this patent and no ex parte reexamination certificate. Those are negative search results, not affirmative findings.
Strategic summary
Claim status: everything is untested at the PTAB. No claim of US 7,049,102 has been canceled, confirmed, or otherwise adjudicated by the Board. That is categorically different from a patent that has "survived two IPRs" — there is no Board-issued validity holding to leverage in either direction, no estoppel, and no FWD to cite. If you are being accused, you cannot point to a canceled claim, and the patent owner cannot point to a confirmed claim.
Estoppel landscape: § 315(e) estoppel is inapplicable. Because no petition was ever instituted and no final written decision ever issued, no petitioner, real party in interest, or privy is estopped from anything. There is accordingly no § 315(e)(2) bar on any prior-art ground — § 102 and § 103 defenses built on patents, printed publications, on-sale activity, public use, or "known or used" prior art remain fully available in district court. Conversely, nothing in the ODP record suggests any third party has done the invalidity work for you.
Pattern signals: none, for a mundane reason. No repeat petitioner, no joinder chain, no defensive aggregator (e.g., Unified Patents) in the record, and no aggressive patent-owner PTAB appeal posture at the Board. The patent owner is a university research foundation, and the record shows a government-interest confirmatory license — the classic profile of a foundational single-cell RNA-amplification patent (the "Eberwine"/aRNA family, cited extensively in later linear-amplification and microarray patent literature) that was licensed broadly rather than litigated at the PTAB.
The important framing point: the absence of PTAB activity here is not the "well-asserted patents eventually attract IPRs" signal. It is a date artifact. This patent's enforceable window closed before AIA trials became a practical tool.
Recommended next steps
- Verify the expiration date first — this is dispositive of almost everything. Pull the face of the patent and the PatentCenter/ODP record and confirm the actual expiration (including any Patent Term Adjustment) and the maintenance-fee history. If the patent expired in 2009, then under 35 U.S.C. § 286 any damages window (six years back from suit) would fall entirely after expiration, leaving no infringing conduct to reach — and no injunctive relief is available for an expired patent. Source: https://patents.google.com/patent/US7049102/en · USPTO PatentCenter: https://patentcenter.uspto.gov · ODP: https://data.uspto.gov
- If you nonetheless face a demand, treat it as a paper-invalidity problem, not a PTAB problem. With no IPR estoppel in play, the full prior-art universe is on the table, and the on-sale/public-use/known-or-used prongs are available rather than being reserved. The published work predating the 1989-09-23 priority date (e.g., the antisense-RNA-synthesis and in-vitro-transcription literature cited on the face of the patent) is the natural starting point.
- Check the family, not just the '102. US 5,545,522; 5,716,785; 5,891,636; and US 6,291,170 share the same § 120 chain and, on the same analysis, would have expired on or about the same date. I did not verify each family member individually in this exercise; if a demand letter cites one of those numbers instead, run the same expiration check before anything else.
- Confirm the negative. A targeted docket search (CourtListener: https://www.courtlistener.com; PTAB E2E / Patent Trial and Appeal Board End-to-End: https://ptacts.uspto.gov) for "7,049,102" returned nothing relevant in my searches. If you need a citable clearance record, capture the PTAB E2E search results page and the ODP "no proceedings" response as evidence of the negative, dated 2026-09-27.
One-line answer for a defendant: there are no AIA trial proceedings on US 7,049,102 — none ever — and the patent's listed expiration of 2009-09-23 means the absence is the least of your concerns; the expiration is your defense.
Generated 9/27/2026, 6:32:26 PM
Ownership chain (2)
Asserters network →Structured records extracted from the assignment-history narrative below. Each entity links to its full ownership-network profile.
? · recorded 2003-09-29 · Assignment
Van Gelder, Russell N.; Von Zastrow, Mark E.; Barchas, Jack D.; Eberwine, James H.Board of Trustees of the Leland Stanford Junior University
? · recorded 2008-11-14 · License
Stanford UniversityNational Institutes of Health (NIH), U.S. Department of Health and Human Services
Assignment history
Inventors, original assignee, and the chain of ownership recorded with the USPTO — including the correspondent attorney who recorded each assignment, since shell-LLC chains often share one repeat-player attorney even when the entity names look unrelated. Surfaces NPE / patent-troll patterns: shell-entity transfers, known asserters in the chain, repeat correspondent fingerprints, pre-litigation assignments, and bankruptcy fire-sales.
I'll work through this systematically. Let me first try to pull the actual USPTO Assignment Center records for this patent number.
Let me look for the assignment record in indexed USPTO assignment databases.
Let me try direct queries against the assignment databases and the correspondent of record.
I hit the tool-call limit before I could pull the literal reel/frame entries from the Assignment Center, so I'll report only what is grounded in the authoritative patent text, the Google Patents legal-events panel, and the Justia patent-history data, and I'll clearly mark what I could not verify rather than fill the gaps.
Method note / honest limitation. I could not retrieve reel/frame numbers, execution dates, or the correspondent of record for US 7,049,102 from USPTO Assignment Center or from any index (Plainsite, Justia, Google Patents assignments panel). What I can report is the set of assignment-type events that appear on the patent record. I did not invent reel/frame placeholders to fill the format.
Inventors
Four named inventors (all listed on the face of the patent, Justia "Patent History"):
| Inventor | Address of record at filing | Employer at time of filing (inferred) |
|---|---|---|
| Russell N. Van Gelder | Des Peres, MO | Washington University in St. Louis area (MO) — inferred from address; not verified |
| Mark E. Von Zastrow | San Carlos, CA | University of California, San Francisco (UCSF) — inferred; not verified |
| Jack D. Barchas | Philadelphia, PA | Not verified (address is Philadelphia; Barchas's institutional home around 2000 is commonly reported as Cornell/Weill Cornell, NY — the mismatch is reported literally, not reconciled) |
| James H. Eberwine | Philadelphia, PA | University of Pennsylvania (Philadelphia) — consistent with address; not independently verified |
Unusual pattern — flagged. This patent's earliest priority is 1989-09-22 (application 07/411,370, filed from the Eberwine lab at Stanford), but the 09/713,545 application was not filed until 2000-11-15 — roughly 11 years later. By the 2000 filing date, none of the four inventors' addresses of record is at Stanford; they are at institutions in Missouri, California, and Pennsylvania. So the "all inventors departed the original assignee" pattern is present here, but the driver is a long continuation chain of a university invention, not a portfolio fire-sale. Corroborating this: the inventors' assignment to Stanford was not recorded until 2003-09-29, roughly three years after filing — a late-recorded confirmatory/administrative assignment typical of universities cleaning up chain of title, not a distress transfer.
Original assignee
- Entity on the issued patent: Board of Trustees of the Leland Stanford Junior University (original applicant of record: "Leland Stanford Junior University"). The "Board of Trustees" is Stanford's legal name — this is not a change-of-name event.
- Primary line of business: Non-profit research university / technology-transfer (Office of Technology Licensing). It is not a product manufacturer.
- Did Stanford ship a product embodying the claims? No. Stanford is a licensor. The claimed subject matter — aRNA amplification with a promoter-bearing primer (the "Eberwine"/T7 method) — is nonetheless heavily practiced by third parties; e.g., NCBI GEO sample GSM4212895 records that "Biotin-labeled complementary RNA (cRNA) was prepared … by the method of Van Gelder et al., US Patent 7049102." That is evidence of use-by-licensees/practitioners, not evidence that the assignee itself commercialized.
- Current status: Operating (university). The patent is Expired – Fee Related, anticipated expiration 2009-09-23 (20 years from the 1989 priority), per the Google Patents legal-status panel.
Assignment timeline
The Assignment Center records for this patent were not retrievable by me, so I cannot give reel/frame, execution date, or correspondent. The following events are those that appear on the patent's recorded legal-events panel (Google Patents). Treat reel/frame as unverified.
Executed: not retrieved / recorded 2003-09-29 — Reel not retrieved / Frame not retrieved
- Conveyance: Assignment of Assignors' Interest (assignment)
- Assignor: Van Gelder, Russell N.; Von Zastrow, Mark E.; Barchas, Jack D.; Eberwine, James H.
- Assignee: Board of Trustees of the Leland Stanford Junior University
- Correspondent: not retrieved (attorney of record for the patent is listed by Justia as The Luther Law Firm; whether that firm was the recording correspondent on this reel/frame is unconfirmed)
- Context: internal/administrative confirmation of title — inventors who had long since left Stanford assigning their rights to the university; not a fire-sale.
Executed: not retrieved / recorded 2008-11-14 — Reel not retrieved / Frame not retrieved
- Conveyance: License — Executive Order 9424 Confirmatory License (this is a license, not an assignment of title)
- Assignor: Stanford University
- Assignee: National Institutes of Health (NIH), U.S. Department of Health and Human Services (the "U.S. Government")
- Correspondent: not retrieved
- Context: statutory Bayh-Dole / E.O. 9424 acknowledgment of the government's funded-invention rights (NIH contract MH23861, recited on the patent face). Does not convey ownership and does not change the assignee of record.
If the Assignment Center holds no additional records beyond the above, that is itself the finding: apart from the original inventors→Stanford assignment and the government's confirmatory license, there is no post-issuance assignment of title, which ordinarily means the original assignee (Stanford) still owns the patent.
Timeline diagram
timeline
title Ownership of US 7049102
1989 : Earliest priority date
2000 : Application filed by Stanford
2003 : Four inventors assign to Stanford
2006 : Patent granted
2008 : NIH confirmatory license recorded
2009 : Patent expired for failure to pay fees
NPE / troll-pattern signals
Shell-entity transfer — not present. No assignee with an "IP / Patents / Holdings / Ventures / Licensing" suffix appears anywhere in the chain. The only title assignee is a university; the only other recorded party is a U.S. federal agency taking a license. No single-purpose LLC, no registered-agent address.
Known asserter in the chain — not present. Neither the original assignee (Board of Trustees of Leland Stanford Junior University) nor the recordable party (NIH/DHHS) appears on any public NPE list (Acacia, Marathon, IV, IPNav, Wi-LAN, Conversant, Vringo, Pendrell, Innovatio, MPHJ, Lumen View, Round Rock, DGC, Spangenberg entities, etc.). No such entity appears in the 2003-09-29 or 2008-11-14 events.
Repeat correspondent across the chain — unclear / insufficient data. I could not retrieve the correspondent of record for either recorded event, so I cannot test for recurrence. This signal is not supportable either way on the data I have. (The patent's prosecution attorney of record is listed as The Luther Law Firm per Justia, but a prosecution attorney-of-record is not the same as an assignment-recording correspondent, and a single appearance would not be a finding anyway.)
Cascading transfers — not present. Only one title-conveying assignment is recorded (2003), against a 2000 filing and 2006 grant. There is no chain of LLC-to-LLC transfers within 24 months; the gap from grant (2006-05-23) to the next recorded event (2008-11-14, a license) is ~2.5 years.
Pre-litigation transfer — not present. No infringement suit naming this patent was identified in the earlier litigation review. The last recorded event (2008-11-14) is a government license, not a transfer to an asserter, and the patent expired 2009-09-23.
Bankruptcy fire-sale — not present. No Chapter 7/11 assignor; the original assignee is a solvent university.
Privateering — not present. No operating company transferred the patent to an NPE for assertion. The only non-university party is the U.S. government taking a Bayh-Dole confirmatory license (which is a retention-of-rights mechanism, the opposite of privateering).
Defensive aggregator (anti-NPE) — not present. The chain does not terminate at RPX, AST, LOT, Unified Patents, or OIN. (The 2008 NIH entry is a federal confirmatory license under E.O. 9424, which should not be miscategorized as a defensive aggregator.)
Verdict
Insufficient data — driven by my inability to retrieve the actual Assignment Center reel/frame records, not by any evidence of an NPE chain.
Justification: The only recorded title transfer is the 2003-09-29 inventors→Board of Trustees of Leland Stanford Junior University assignment, followed by a 2008-11-14 Executive Order 9424 confirmatory license of record to NIH/DHHS (a license, not a conveyance). There is no shell-entity transfer, no known-asserter assignee, no cascading LLC chain, and no pre-litigation transfer in the record I can see; the earlier litigation review found no suit asserting this patent, and it expired for fee non-payment on 2009-09-23. Under the defined categories, the honest call is Insufficient data (only the original assignment), with a strong lean toward "university-owned, never-asserted." If the Assignment Center returns additional reel/frame entries, re-run signals 2–4 before finalizing.
Verify at: USPTO Assignment Center search for patent 7,049,102 — https://assignmentcenter.uspto.gov/ (historical interface: https://assignment.uspto.gov/patent/index.html). Search by patent number and by assignor names (Van Gelder; Von Zastrow; Barchas; Eberwine) to capture any reel/frame I could not surface here.
Cross-reference discrepancy flagged. The earlier Patent-summary section stated there was "no assignee change of record beyond Stanford→Board of Trustees." That phrasing is imprecise: the 2003-09-29 event is an inventors→Board of Trustees assignment, and "Board of Trustees" is Stanford's legal name, so there was never a separate Stanford→Board-of-Trustees transfer. No other contradiction with the prior sections was found; the priority-date discrepancy (1989-09-22 vs. 1989-09-23) remains as previously reported and uncorrected.
Generated 9/27/2026, 6:32:43 PM
Prior art
Earlier patents, publications, and products that may anticipate or render the claims unpatentable.
I'll research the prior-art citations for US 7,049,102. Let me run several targeted searches.
Let me retrieve the actual cited references list for this patent.
Let me pull the front-page reference lists from US 7,049,102 and its parent patents directly.
Prior Art Analysis — US 7,049,102 B1 ("Multi-gene expression profile")
0. Sourcing and verification note (read first)
What I could verify. I confirmed that the literal number 7049102 maps to US 7,049,102 B1, "Multi-gene expression profile," app. 09/713,545, filed 2000‑11‑15, granted 2006‑05‑23, inventors Van Gelder / Von Zastrow / Barchas / Eberwine, assignee Board of Trustees of Leland Stanford Junior University, priority 1989‑09‑22 (Google Patents; Espacenet bibliographic record for US7049102 (B1) ― 2006-05-23). I did not substitute any similar number.
What I could not fully verify — and why it matters here. The authoritative Google Patents text supplied earlier truncates inside the specification and does not contain the front‑page "(56) References Cited" block. My U.S. patent‑reference list below is therefore drawn from the freepatentsonline front‑page record of the immediate family member US 5,891,636 (same specification, same examiner art, continuation chain to the 1989 application), plus the Justia record for 7049102 for the non‑patent ("Other References") list, plus the EPO/Espacenet family record. Treat the patent‑citation set as family‑level ground truth, cross‑checked for consistency, not as a byte‑accurate transcription of the 7049102 printed front page. Where a value could not be confirmed I say so rather than fill it in.
Critical caveat on the § 102 question you asked. You asked which claim(s) each reference "potentially anticipates." The earlier Patent summary already flagged that the literal claim text was never retrieved and its numbering/exact wording is unverified. I therefore map each reference to the four independent process families identified earlier (Core amplification; Gene‑expression detection in a preselected cell population; Subtractive hybridization probe; cDNA library construction), and I label every mapping as potential — a § 102 anticipation conclusion cannot be stated as fact without reading the claims, and several of these references are, on their face, not § 102 art at all (see the "own‑family" rows).
One legal threshold to keep in mind throughout. Because of the unbroken § 120 chain back to application 07/411,370 (1989), the effective critical date is 1989‑09‑22. Under pre‑AIA § 102:
- § 102(b) statutory bar → reference must predate 1988‑09‑22 (one year before the 1989 filing).
- § 102(a) → reference must predate the invention (≈1989‑09‑22).
- § 102(e) → a U.S. patent granted on an application filed before 1989‑09‑22 qualifies as of its filing date.
These dates matter because the family was granted in the 1990s–2000s while the art that actually threatens it is 1983–1989 vintage.
1. U.S. patent references (front‑page citations)
The following eleven U.S. patents appear in the cited‑reference list of the family record (FPO front page of US 5,891,636, the direct parent of 7049102). Issue dates are as listed; filing dates are marked where unverified.
| # | Citation | Date | Brief description | Potential § 102 effect vs. 7049102 |
|---|---|---|---|---|
| 1 | US 4,683,202 — Mullis, "Process for amplifying nucleic acid sequences" | issued 1987‑07‑28 (filing ~1985, exact date not verified) | The original PCR patent — repeated primer‑extension/dissociation cycles producing exponential DNA copies. | § 102(b) art, but not anticipatory on its face. It discloses primer extension and amplification, but by DNA replication, not promoter‑driven transcription of aRNA. It also cannot meet the "primer linked to an RNA‑polymerase promoter in anti‑sense orientation" and "transcribing anti‑sense RNA" limitations of process family 1, nor families 2–4. Relevant only as background/§ 103 art. |
| 2 | US 4,683,195 — Mullis et al., "Process for amplifying, detecting, and/or cloning nucleic acid sequences" | issued 1987‑07‑28 | Companion PCR patent (detection/cloning aspects). | Same analysis as #1. § 102(b) art; not anticipatory of the aRNA claims — no transcription step, no promoter–polymerase pair. |
| 3 | US 4,981,783 — Augenlicht, "Method for detecting pathological conditions" | issued 1991‑01‑01 | Nucleic‑acid‑based detection of pathological (e.g., colonic) conditions. | Not § 102 art with respect to its issue date, and on its face it is a detection method, not an amplification/transcription process. No anticipation of families 1–4. Its cognate #4 below is likewise diagnostic. |
| 4 | US 5,085,983 — Scanlon, "Detection of human tumor progression and drug resistance" | issued 1992‑02‑04 | Diagnostic method for tumor progression/drug resistance. | Detection/diagnostic; assumes rather than teaches aRNA amplification. No anticipation. |
| 5 | US 5,057,410 — Kawasaki et al., "Chimeric messenger RNA detection methods" | issued 1991‑10‑15 | Methods for detecting chimeric mRNA species. | RNA detection; no RNA‑polymerase‑promoter amplification paradigm. No anticipation. |
| 6 | US 5,130,238 — Malek et al., "Enhanced nucleic acid amplification process" | issued 1992‑07‑14 (filing date unverified — controlling question; this is the 3SR/NASBA‑type transcription‑based amplification line) | Transcription‑based amplification: incorporates an RNA‑polymerase promoter into a cDNA and generates multiple RNA copies by RNA polymerase — the closest patent analog to the 7049102 concept. | The strongest patent‑reference § 102 candidate. If its underlying application was filed before 1989‑09‑22, it is § 102(e) art as of that filing date. It could potentially anticipate broad claims in process family 1 (promoter‑driven generation of multiple RNA copies from a cDNA template). It is distinguishable because it is a self‑sustained (3‑enzyme/cyclic) reaction requiring a second primer, whereas 7049102 claims a one‑direction primer‑promoter complex with a single transcription round; those distinctions will live in the claim language (not verified). Flagged as the reference most worth obtaining in full. |
| 7 | US 5,281,519 — Schechter et al., "Simple, rapid and reliable method for detecting thalassemia" | issued 1994‑01‑25 | Genetic diagnosis of thalassemia. | Notable because the 7049102 specification expressly invokes thalassemia/hemoglobin‑level diagnosis as a use case. But it is a diagnostic method, not an amplification invention → no anticipation; background only. |
| 8 | US 5,514,545 — Eberwine, "Method for characterizing single cells based on RNA amplification for diagnostics and therapeutics" | issued 1996‑05‑07 | Single‑cell characterization via RNA amplification — a sibling technology of the same inventor group. | Same‑inventor / same‑laboratory family. Because it was filed after the 1989 priority, it is not § 102(e) prior art against 7049102; and being the applicant's own work post‑dating the invention it is not § 102(a)/(b) art either. No anticipation. (It is, however, frequently cited as prior art by other, later patents — e.g., US 6,132,997 and US 5,932,451 — which is a common source of confusion.) |
| 9 | US 5,545,522 — Van Gelder et al., "Process for amplifying a target polynucleotide sequence using a single primer‑promoter complex" | issued 1996‑08‑13 (from 07/957,647, 1992, itself a continuation of 07/411,370, 1989) | The family matriarch — the original grant of the aRNA/single primer‑promoter paradigm. | Not prior art against 7049102. It is the same disclosure by the same inventive entity in the direct § 120 chain; a continuation is not anticipated by its own parent. Appears in the citation list as an internal/related reference. |
| 10 | US 5,716,785 — Van Gelder et al., "Processes for genetic manipulations using promoters" | issued 1998‑02‑10 | Family member (continuation of 08/636,748 → 07/957,647 → 07/411,370). | Same analysis as #9 — own family, not prior art. |
| 11 | US 5,569,584 (source rendered it "5569584") — Augenlicht, "Method for distinguishing or monitoring the state of premalignant or malignant transformed human colonic tissue" | issued 1996‑10‑29 | Colonic‑tissue state monitoring/quantitation. | Diagnostic/quantitative tissue method; no aRNA amplification teaching. No anticipation. (Number as rendered by the source; I did not auto‑correct it.) |
Note on rows 9–11: the front‑page list mixes true third‑party art (rows 1–8, 11) with the applicant's own family members (rows 9–10). Only rows 1–8 and 11 are even candidate prior art, and only row 6 (US 5,130,238) raises a real § 102 question.
Foreign patent documents
The Espacenet record for US7049102 (B1) states "No documents available for this priority number," and the Google Patents record shows no foreign‑patent (56) citations. I found no foreign patent documents cited. (The PCT/ISA search reports that surfaced in my searches — e.g., WO 95/11773, WO 95/01241, GB 896,910 — belong to unrelated abrasive‑article technology and must not be attributed to this patent.)
2. Most § 102‑relevant non‑patent literature
The Justia record for 7049102 carries a large "Other References" list (alphabetically M–S in the portion retrieved: Milligan, Milner, Motoyama, Murakawa, Nakai ×4, Noma, O'Malley, Ohara, Okayama ×2, Palazzolo, Polites, Portela, Pruitt, Putney, Rabkin, Saiki…) that tracks the family's "Other References" list beginning A–E (Behnam, Belldegrun, Belyavsky, Berger, Chan, Chang, Chicurel, Craig, Davis, Eberwine…). The items below are the ones with genuine § 102 teeth against the four process families:
| Reference | Date | Brief description | Potential § 102 effect |
|---|---|---|---|
| Noma, Y. et al., "Cloning of cDNA encoding the murine IgG1 induction factor by a novel strategy using SP6 promoter," Nature 319:640‑646 | 1986 | Clones cDNA using an SP6 promoter fused to the primer to drive RNA transcription as part of the cloning strategy. | § 102(b) art (predates 1988‑09‑22) and the single most potent non‑patent item. It discloses promoter‑linked primer + transcription of RNA from the cDNA — potentially anticipating broad claims of process family 1 and, by extension, the library‑construction family (4). Distinguishing features will turn on the specific primer‑promoter architecture and claimed workflow (claim text unverified). |
| Sarkar, G. et al., "RNA amplification with transcript sequencing (RAWTS)," Science 244:31‑34 | 1989 | Attaches a T7 phage promoter to a PCR primer; PCR‑amplifies cDNA; transcribes with T7 RNA polymerase to make RNA for sequencing. Expressly discussed in the 7049102 BACKGROUND as the closest art. | § 102(a) candidate (published before 1989‑09‑22; likely not § 102(b) given the ~April 1989 date). Potentially anticipates family 1 if the claims do not require transcription without prior PCR. Caveat: RAWTS requires two PCR primers / PCR amplification; the 7049102 claims (per the Summary) recite a single primer‑promoter complex and direct transcription — so this is a § 103‑flavored near‑miss on the verified record. |
| Palazzolo, M.J. et al., "A family of lambda phage cDNA cloning vectors … allowing the amplification of RNA sequences," Gene 52:197‑206 | 1987 | Phage‑promoter cDNA cloning vectors permitting amplification of RNA sequences. | § 102(b) art. Potentially anticipatory of the cDNA library family (4) and of the general "promoter → RNA amplification" concept in family 1, to the extent the claims read on vector‑based (rather than primer‑based) promoter incorporation. |
| Ohara, O. et al., "One‑sided polymerase chain reaction: the amplification of cDNA," PNAS 86:5673‑5677 | 1989 | Single‑sided PCR for cDNA amplification. | § 102(a) candidate (publication date vs. 1989‑09‑22 unverified). Relevant to the "one primer need be known" advantage recited in the specification; not a transcription‑based teaching, so a near‑miss to families 1/2. |
| Melton, D.A. et al., "Efficient in vitro synthesis of biologically active RNA … by SP6 RNA polymerase," Nucl. Acids Res. 12:7035‑7056 | 1984 | In vitro transcription from plasmid vectors with SP6 RNA polymerase; basis for the high‑specific‑activity probe concept. | § 102(b) art. Teaches the transcription half of the invention (promoter‑driven RNA synthesis). Potentially anticipates any claim that reads on promoter‑driven transcription absent the primer‑linked (non‑vector) limitation. Directly cited in the 7049102 specification as the general‑characteristics reference for amplification. |
| Milligan, J.F. et al., "Synthesis of small RNAs using T7 RNA polymerase," Methods Enzymol. 180:51‑62 (and the companion Nucl. Acids Res. 15:8783‑8798, 1987 piece) | 1989 / 1987 | T7 RNA polymerase‑driven synthesis of RNA transcripts. | § 102(a)/(b) art as applicable. Establishes T7‑polymerase transcription as known; supports obviousness more than anticipation. |
| Gubler, U. & Hoffman, B.J., "A simple and very efficient method for generating cDNA libraries," Gene 25:263‑269 | 1983 | RNase H / E. coli DNA polymerase I second‑strand cDNA synthesis — the exact method the 7049102 claims/specification use. | § 102(b) art. Anticipates nothing alone (it lacks any promoter/transcription element) but is the anchor § 103 reference for the second‑strand step of family 1; the claim cannot be anticipated by it. |
| Duguid, J.R. et al., PNAS 85:5738‑5742 | 1988 | Biotinylated‑RNA subtractive hybridization. | § 102(b) art against the subtractive‑probe family (3) background; on its face subtractive hybridization per se, not promoter‑amplified subtractive probes → near‑miss/§ 103. |
| Frohman, M.A. et al., PNAS 85:8998‑9002 | 1988 | 3′ RACE / homopolymeric tailing for amplifying unknown cDNA ends. | § 102(b) art; cited in the 7049102 BACKGROUND as the art the invention improves upon. No promoter‑transcription teaching. |
| Sive, H.L. & St. John, T., Nucl. Acids Res. 16:10937 | 1988 | Biotin‑labeled RNA probe synthesis. | § 102(b) art for the labelling embodiment; not anticipatory of the amplification process. |
| Tecott, L.H. et al., Science 240:1661‑1664 | 1988 | In situ transcription (IST) — the single‑cell cDNA capture technique the 7049102 examples build on. | § 102(b) art. Relevant to the single‑cell/preselected‑population family (2) as the starting method; it does not itself disclose promoter‑driven aRNA amplification → no anticipation. |
| Okayama, H. & Berg, P., Mol. Cell. Biol. 2:161‑170 (1982) and 3:280‑289 (1983) | 1982 / 1983 | High‑efficiency full‑length cDNA cloning vector systems. | § 102(b) art against the library family (4); vector‑based, no primer‑linked promoter → near‑miss. |
| Belyavsky, A. et al., Nucl. Acids Res. 17:2919‑2932 | 1989 | PCR‑based cDNA libraries from a few cells. | § 102(a) candidate; relevant to family 4's "extremely limited tissue" purpose, but PCR‑based (not transcription‑based) → near‑miss. |
Remaining "Other References" (Berger 1983; Chan 1986; Chang 1977; Chicurel 1993; Craig 1993/1997; Davis 1995; Milner 1983; Motoyama 1989; Murakawa 1988; Nakai 1986 ×4; O'Malley 1985; Polites 1988; Portela 1985; Pruitt 1988; Putney 1983; Rabkin 1988; Saiki, etc.) are § 102(b)/(a) background art that individually lack a promoter‑linked‑primer + anti‑sense‑RNA‑transcription teaching and do not anticipate any of families 1–4. The T7/T3/SP6 polymerase‑replication references (Nakai ×4, Rabkin 1988) are § 103 fodder for the selection of T7 as the polymerase.
3. Prior art cited inside the 7049102 specification
Independent of the front page, the specification itself names: US 4,683,202 and US 4,683,195 (Mullis — PCR), US 4,755,619 (labelling), and US 4,458,066 (solid‑support oligonucleotide synthesis). As in the earlier summary, these are applicant‑acknowledged background; only 4,683,202/195 have any § 102(b) weight, and neither anticipates (see § 1 above).
4. Bottom line — ranked § 102 relevance
- US 5,130,238 (Malek et al.) — strongest patent‑reference candidate. Transcription‑based amplification using an RNA‑polymerase promoter; potentially anticipates broad claims in process family 1 if its application predates 1989‑09‑22 (filing date unverified — verify this first).
- Noma et al., Nature 319:640‑646 (1986) — strongest non‑patent candidate. SP6‑promoter‑driven cDNA cloning/transcription; § 102(b) art; potentially anticipates family 1 and family 4 claims.
- Palazzolo et al., Gene 52:197‑206 (1987) and Melton et al., NAR 12:7035‑7056 (1984) — § 102(b); each supplies half of the paradigm (vector‑based promoter amplification; promoter‑driven in vitro transcription) and together are potent § 103 combinations.
- Sarkar et al., Science 244:31‑34 (1989) — § 102(a) near‑miss; the specification's own closest admitted art; distinguishes on the PCR‑intermediate requirement.
- Everything else (Mullis PCR patents; the Augenlicht/Scanlon/Kawasaki/Schechter diagnostics; Gubler‑Hoffman; Duguid; Frohman; Tecott; Okayama‑Berg; Belyavsky) is § 102(b)/(a) background that does not anticipate the aRNA process families.
Not prior art at all: US 5,545,522 and US 5,716,785 (the applicant's own § 120 parents) and US 5,514,545 (same inventor group, filed post‑priority). They appear only as related/internal citations.
5. Explicit uncertainty flags (please carry these forward)
- The 7049102 front‑page "(56) References Cited" block was not in the supplied authoritative text and I could not retrieve it directly. The U.S. patent list above is the family record (FPO front page of US 5,891,636) plus the Justia "Other References" list for 7049102. It is highly likely identical or near‑identical to the 7049102 list, but that identity is an inference, not a verified transcription.
- Claim text is still unverified (carried over from the earlier Patent summary). Every "potentially anticipates [family N]" statement is a mapping to the four Summary‑of‑the‑Invention process families, not a claim‑by‑claim § 102 conclusion. Claim count/numbering remain unconfirmed (Google Patents indexing suggests a set of at least 45 claims).
- US 5,130,238's filing date is the single highest‑value fact to confirm. Without it, its § 102(e) status is unresolved.
- Publication dates for the 1989 references (Ohara, Belyavsky) are asserted at the year level only; whether they fall before 1989‑09‑22 is unverified and determines § 102(a) vs. non‑art.
- The number rendered as "5569584" in the FPO source is reported as it appears; I did not auto‑correct it.
- No foreign patent documents are cited for this number (Espacenet: "No documents available for this priority number").
- If you need a byte‑accurate (56) list, retrieve the USPTO PatentCenter IFW front page (PGPub/patent full text) for 09/713,545 or the PDF of US 7,049,102 B1 itself — neither was accessible in this session.
Generated 9/27/2026, 6:33:11 PM
Obviousness
Combinations of prior art that suggest the claimed invention would have been obvious under 35 U.S.C. § 103.
I'll research the prior-art landscape for this patent before building the § 103 analysis.
Let me retrieve the claim text and the prosecution prior-art citations for this family.
Let me pull the actual claim set and the examiner-cited references for this family.
Obviousness Analysis — U.S. Patent No. 7,049,102 B1 ("Multi-gene expression profile")
0. Scope, and a correction to the prior section
This analysis builds on the previously generated "Patent summary" and "Litigation summary." One item from the earlier summary needs correction before I proceed, because it bears on claim scope and hence on the § 103 analysis:
Flagged contradiction. The earlier summary inferred "a set of at least 45 claims" from Google Patents' indexed term frequencies (e.g., "nucleic acids … claims description 45"). That inference is not sound. The Google Patents concept table reports the total number of occurrences of a term across the claims and the description — the "45" is a hit count, not a claim count. So the "at least 45 claims" statement should be withdrawn; the claim count remains unverified.
I also could not retrieve the literal claim text in the searches available to me (the authoritative text supplied is truncated before the claims; Justia returns only bibliographic data and a "FIG. 6" fragment). My analysis therefore proceeds against (a) the four process families recited in the SUMMARY OF THE INVENTION, and (b) the dependent-subject-matter clusters visible in the concept table (cell/tissue types, blot formats, labels). Where a conclusion depends on exact claim language I say so.
Because Google Patents lists the primary examiner as James Ketter and the patent issued May 23, 2006 as a straight continuation (no reissue/reexam recorded), the claim set as issued almost certainly tracks the SUMMARY text, which is the same four-process architecture as its parents US 5,545,522 → 5,716,785 → 5,891,636 → 6,291,170.
1. Legal framework
Under 35 U.S.C. § 103 and Graham v. John Deere Co., 383 U.S. 1 (1966), I determine (i) the scope and content of the prior art, (ii) the differences between the prior art and the claims, (iii) the level of ordinary skill, and (iv) secondary considerations. Under KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007):
- A combination is obvious if a PHOSITA would have had a reason to combine the references with a reasonable expectation of success, even absent an express teaching to combine.
- Where a technique is used to improve one of a finite number of identified, predictable solutions, it is obvious.
- "[A]ny need or problem known in the field … and addressed by the patent can provide a reason for combining the elements."
- A known technique applied to a known method yields an obvious result.
PHOSITA here: an M.S./Ph.D. molecular biologist with ~2–4 years' bench experience in recombinant DNA, conversant with Maniatis et al., Molecular Cloning (1982) as the standard protocol source, with routine familiarity with cDNA synthesis, restriction/cloning, and phage-RNA-polymerase in vitro transcription.
2. The references to be used (the "Prior Art" section of the page)
The page's DEFINITIONS section is, in substance, the patent's own admitted prior art. Those citations are prior art under § 102(a)/(b) — all predate the Sept. 22, 1989 earliest priority date. Grouping them by function:
| Ref. | Teaching as cited in the patent | Relevance |
|---|---|---|
| Gubler & Hoffman, Gene 25:263–269 (1983) | Second-strand cDNA synthesis using RNase H + E. coli DNA polymerase I | Converts first-strand cDNA to ds-cDNA — the step that regenerates the double-stranded promoter |
| Melton et al., Nucl. Acids Res. 12:7035–7056 (1984) | In vitro synthesis of RNA hybridization probes from plasmids bearing a phage (SP6) promoter | The core "transcribe RNA off a promoter-bearing DNA template" teaching |
| Krieg et al., Nucl. Acids Res. 12:7057–7070 (1984) | Functional mRNA by SP6 transcription of cloned cDNA | Confirms promoter-driven transcription works on cDNA-derived templates |
| Dunn & Studier, J. Mol. Biol. 166:477–535 (1983) (and 175:111–112) | T7 promoter consensus from −17 to +6 | Supplies the specific promoter sequence operably linked to the primer |
| Chamberlin & Ryan, The Enzymes (1982), pp. 87–108 | Polymerase/promoter specificity | Establishes that phage polymerases are promoter-specific — enables sequential use of two different promoters |
| Sarkar et al., "RAWTS," Science 244:331–334 (1989) | Promoter-tagged-primer cDNA synthesis → amplification → T7 transcription → sequencing | Closest prior art; expressly cited in the patent's BACKGROUND |
| Stofler [Stoflet] et al., Science 239:491–494 (1988) | GAWTS — same promoter-tag/amplify/transcribe architecture | Same |
| Mullis, U.S. 4,683,202 / 4,683,195 | PCR | The alternative amplification route the patent distinguishes |
| Frohman et al., PNAS 85:8998–9002 (1988) | 3′/5′ RACE via homopolymeric tailing | Amplification without terminus knowledge |
| Eberwine et al., Neuroscience Short Course I 69–81 (1988) | Converted single-cell/tissue cDNA into amplifiable material | The inventors' own pre-priority publication |
| Tecott et al., Science 240:1661–1664 (1988) | In situ transcription (IST) — cDNA synthesis in situ in fixed tissue sections/cells | Basis for the single-cell/tissue-section claims |
| Duguid et al., PNAS 85:5738–5742 (1988) | Subtractive hybridization using biotinylated RNA | Basis for the subtractive-probe family |
| Sive & St. John, Nucl. Acids Res. 16:10937 (1988) | Biotin-labeled nucleotides incorporated into RNA | Basis for the label limitations |
| U.S. 4,458,066 (Caruthers); Beaucage et al., Tetrahedron Lett. (1981); U.S. 4,755,619 | Solid-phase oligo synthesis; labeling techniques | Makes the claimed primer complex routine to make |
| Maniatis et al., Molecular Cloning (1982) | Standard procedures for all cloning/hybridization steps (expressly incorporated by reference in the spec) | Renders every routine downstream step conventional |
Citation-accuracy note (reported literally, not auto-corrected). The patent text reads "Stofler, et al., Science 339: 491 (1988)," "Sarkar et al., Science 244: 31–34 (1989)," and "Jones et al., J. Biol. Chem. 262: 1421–14249 (1987)." The search-corroborated citations are Science 239:491–494; Science 244:331–334; and JBC 262:14241–14249. I interpret the patent's identifiers literally, but the substantive identity of each reference is not in doubt. The same is true of "Beaucage … Tetrahedron Letters 22: 1359–1962," which is the well-known Tetrahedron Lett. 22:1859–1862 (1981) paper.
Two additional references appear in the family's own prosecution record (Unified Patents listing for the parent US 5,545,522: https://portal.unifiedpatents.com/patents/patent/US-[5545522](/patent/5545522)-A): Hames et al., Nucleic Acid Hybridization, IRL Press (1985); Sargent, Methods in Enzymology vol. 152 (1987) 423–433; and Feinberg & Vogelstein, Anal. Biochem. 132:6–13 (1983) (random-primer labeling). I flag that I retrieved these from secondary listings, not from the file wrapper.
3. The priority-date fork that controls the whole analysis
This is the pivotal § 103 issue and it is independent of claim wording.
The 2000-filed claims receive the Sept. 22, 1989 benefit date only to the extent they are supported by 35 U.S.C. § 112 in the 1989 application (Ser. No. 07/411,370). The four process families paraphrased in the SUMMARY all appear to be supported by the 1989 disclosure — but the title "Multi-gene expression profile," and the 2000 filing date of an 11-year-old continuation chain, create a real risk that the as-issued claims are drawn to subject matter added later (e.g., a profile of multiple genes, quantified relative representation, or specific cell/tissue enumeration not in the 1989 text).
If the claims do not get the 1989 date, an entirely new and much more damaging body of prior art becomes available — including the inventors' own work:
- Van Gelder, von Zastrow, Yool, Dement, Barchas & Eberwine, PNAS 87(5):1663–1667 (Mar. 1, 1990) — https://www.pnas.org/doi/10.1073/pnas.87.5.1663 — discloses the complete aRNA method (T7-promoter/oligo-dT primer → second-strand synthesis → T7 transcription → up-to-80-fold amplification) and detection of "specific messages for moderate-abundance mRNAs for actin and G-protein α subunits," including aRNA from a single cerebellar Purkinje cell.
- Eberwine et al., PNAS 89:3010–3014 (1992) and the ensuing U.S. 5,514,545 (Eberwine, filed Jul. 26, 1993; issued May 7, 1996) — the latter expressly claims "generating an expression profile which inventories RNA present in a specific cell."
Consequence: under this fork, the "multi-gene expression profile" claims would be squarely anticipated or at minimum obvious over the inventor's own 1990 PNAS disclosure combined with the '545 patent — a § 102(b)/§ 103 problem the patentee cannot escape by arguing "same inventors," because one's own prior publication is prior art.
This is the single strongest obviousness posture against the patent and should be checked first against the actual claim language.
4. Combinations that render the claims obvious
Combination A — the core amplification family
References: Melton (1984) + Krieg (1984) + Dunn & Studier (1983) + Gubler & Hoffman (1983) + Sarkar/Stoflet (promoter-tagged primer) [+ Mullis as the known alternative].
Evidentiary mapping.
- Sarkar/Stoflet disclose every element of the independent process except the omission of PCR: (1) first-strand cDNA primed with an oligonucleotide carrying a phage promoter 5′ to the priming sequence; (2) second-strand synthesis reconstituting a double-stranded, functional promoter; (3) transcription with T7 RNA polymerase to make amplified RNA.
- Melton/Krieg establish the predictable, high-yield nature of promoter-driven transcription of any DNA bearing a cognate promoter — including the express teaching that such transcripts are anti-sense and usable as probes.
- Gubler & Hoffman supplies the standard second-strand method that the patent itself uses.
- Dunn & Studier supplies the exact promoter sequence the patent's SEQ ID NO:2 recites.
Motivation to combine (articulated as a PHOSITA would have):
- Known problem, known solution. The field knew PCR (Mullis) and knew its documented limitations — the patent's own BACKGROUND recites low Taq fidelity, propagation of misincorporations, and size-skewing beyond ~3 kb. A PHOSITA seeking linear, low-error, size-representative amplification of a heterogeneous cDNA population had a finite set of predictable options: PCR, or promoter-driven transcription.
- Transcription was already the field's tool for exactly this purpose (Melton 1984; Krieg 1984; Nielsen & Shapiro 1986).
- Sarkar/Stoflet already performed the transcription step on promoter-tagged cDNA; deleting the intermediary PCR step is a simplification of a known method, not a new instrumentality. KSR — "a known technique applied to a known method" / "omission of an element and retention of the function."
- Reasonable expectation of success: Melton 1984 showed the transcription step is processive and yields microgram quantities; nothing in RAWTS suggests the transcription step requires prior PCR — PCR merely supplies more template.
Result: the core independent process is prima facie obvious over Sarkar/Stoflet in view of Melton and Gubler & Hoffman. The patentee's distinguishing argument ("RAWTS uses two primers / requires PCR") is a limitation, not an inventive contribution — it is the removal of a step, which KSR and In re Wu treat as obvious where the remaining steps retain their function.
Combination B — detection of gene expression in a preselected cell population
References: Combination A + Tecott et al. (1988) (in situ transcription) [+ optional Eberwine Neuroscience Short Course 1988].
Tecott discloses cDNA synthesis directly in fixed tissue sections/cells — i.e., the "limited-quantity starting material" problem the patent frames as its motivation. The patent's own SPECIFICATION states the IST reaction conditions are "the same as described in Eberwine et al., Neuroscience Short Course I" and that cDNA for its amplifications "was synthesized by IST." A PHOSITA combining Tecott's IST with Combination A arrives at the claimed detection method with a reasonable expectation of success; the patent's own examples confirm it worked the first time.
For single-cell claims: Van Gelder 1990 (if the priority fork opens) already demonstrates single-Purkinje-cell aRNA; the '545 patent (if art) demonstrates the six-claims/expression-profile method on single cells.
Combination C — subtractive hybridization probe
References: Combination A + Duguid et al. (1988) + Chamberlin & Ryan (1982).
The patent's own SPECIFICATION concedes the subtraction paradigm: "two nucleic acid populations … with one population present in molar excess (driver) … Sequences present in both populations will form hybrids" — citing Duguid. The only additional elements the claim family adds are (i) using aRNA as driver, and (ii) using a second, different promoter (T3/SP6 vs. T7) to re-amplify the unhybridized subpopulation. Element (i) follows directly from Melton's teaching that the transcripts are anti-sense. Element (ii) is nothing more than applying Chamberlin & Ryan's express teaching that polymerases are promoter-specific — a PHOSITA would routinely select non-cross-hybridizing promoter/polymerase pairs to avoid regenerating the first-round product. This is an obvious design choice among a finite, enumerated set (T3, T7, SP6, all named in the patent).
Combination D — cDNA library construction from aRNA
References: Combination A + Efstratiadis et al., Cell 7:279 (1976) / Maniatis et al., Cell 8:163 (1976) (hairpin priming) + Feinberg & Vogelstein (1983) (random-primer labeling) + Maniatis (1982).
The patent states that aRNA "serves … as starting material for cloning procedures using random primers" — random-primed second-strand synthesis is Feinberg & Vogelstein. Converting amplified RNA to a library is the routine application of Maniatis (1982), which the patent incorporates by reference. No unexpected result is asserted.
The kit claims
Combination A + Maniatis (the standard "buffers/enzymes/nucleotides, instructions" assembly) renders kit claims obvious; prepackaging reverse transcriptase, RNA polymerase, and labeled nucleotides was conventional (the patent itself notes T7 polymerase was commercially available from Promega and Epicenter). Aggregating known components with a printed instruction sheet is the paradigm of an obvious kit under KSR.
The dependent claims
These collapse even more easily:
- Tissue sources (blood/T-B cells, brain, spleen, bone, heart, vascular, lung, kidney, liver, pituitary, endocrine glands, lymph node, primary cells, tumor cells) — mere recitation of known biological sources of RNA; Maniatis makes each routine. Choosing among them is not inventive (In re Soni).
- Detection steps (Northern/Southern blotting, probe hybridization) — conventional as of 1989 (Southern 1975; Alwine 1977; Maniatis 1982).
- Label limitations (³²P, ³⁵S, ³H, biotin/avidin) — expressly taught by Melton (1984) (radioactive) and Sive & St. John (1988) (biotin).
- Promoter/primer length ranges (15–250 nt promoter; 10–50 nt primer; 5–50 T residues) — result-effective-variable territory; absent a showing of criticality for the specific endpoints, routine optimization.
- "Degenerate primer pool" limitations — taught by Frohman (1988) and Mullis.
5. Anticipated patentee rebuttals, and why they are weak
| Patentee argument | Why it likely fails |
|---|---|
| "RAWTS requires PCR; we eliminate it" | KSR: omission of a step that retains the function of the remaining steps is obvious; the transcription step is admitted in the patent's own BACKGROUND to be within RAWTS. |
| "aRNA amplification is linear/uniform, unlike PCR" | Linearity is the inherent property of transcription from a fixed template — Melton 1984 already teaches processive transcription. Inherency and predictability cut against the patentee. |
| "Works from a single cell" | Tecott (1988) IST + Van Gelder 1990 (if art) directly teach the single-cell application; and the '545 patent (if art) claims it. |
| "No prior cloning into vectors needed" | Nielsen & Shapiro (1986) and Sarkar/Stoflet already transcribe non-cloned cDNA. |
| "Teaching away from PCR" (Baldwin/Gilbert) | The references do not criticize PCR so much as offer a complementary route; mere preference is not a teaching away. And the patent's BACKGROUND itself lists PCR's drawbacks — evidence the field was already motivated to look elsewhere. |
| "Unexpected results" (secondary considerations) | The only non-obviousness-worthy datum is the degree of amplification (80–1000×), but the patent itself attributes yield to enzyme concentration and incubation time (4-fold gain from 10→80 units) — a result-effective variable, i.e., optimization, not invention. No nexus-based commercial success or licensing is evident in the record (the patent lapsed in 2009). |
6. The threshold defect: subject-matter eligibility is a separate, perhaps stronger attack
Although the task is § 103, I note for completeness that the core claims — directed to hybridizing a primer, extending it with an enzyme, and transcribing RNA — are classic Mayo/Bilski/Myriad-type product-of-nature/manipulation-of-natural-phenomena claims. A PHOSITA-recited "primer complex" comprising a cDNA-derived promoter plus conventional enzymes and nucleotides was, by 1989, a routine laboratory practice, and the claims may be invalid under § 101 independent of any Graham analysis. This bears on the § 103 framing because it reinforces that "the invention" is a combination of known, conventionally practiced techniques.
7. Bottom line
Yes — the claims of US 7,049,102 would be prima facie obvious under § 103.
- Strongest single combination: Sarkar/Stoflet (promoter-tagged-primer transcription) in view of Melton (1984) and Gubler & Hoffman (1983) — with Mullis evidencing the known alternative route the PHOSITA would have abandoned for the linearity reason the patent itself gives up front.
- For the detection/cell-population claims: add Tecott (1988) (and, if the priority date is broken, Van Gelder 1990 PNAS and Eberwine US 5,514,545).
- For the subtractive-probe claims: add Duguid (1988) + Chamberlin & Ryan (1982).
- For the library claims: add Efstratiadis/Maniatis hairpin priming + Feinberg & Vogelstein (1983) + Maniatis (1982).
- For kit and tissue/label/blot dependents: routine aggregation and selection from known options; no nonobviousness.
The patentee's only plausible bulwark is a perfect 1989 priority claim surviving § 112 for the as-issued "multi-gene profile" language. That is the first thing to verify against the actual claim text — and I cannot verify it from the sources available to me.
8. Explicit uncertainty flags
- Claim text not verified. Every claim-numbered statement above is derived from the SUMMARY OF THE INVENTION and the concept table, not from the literal claims. If the as-issued independent claims contain a narrowing limitation not in the 1989 disclosure (e.g., a specific multi-gene quantification algorithm, a particular label chemistry, or a claim to a profile as such), the analysis must be re-run and the priority fork (Section 3) becomes decisive.
- Priority/maintenance facts unchanged from prior sections. Anticipated expiration 2009-09-23; status "Expired – Fee Related"; NIH confirmatory license recorded 2008-11-14. No litigation located against this patent number (consistent with the earlier Litigation summary); I did not verify litigation on the four family members.
- Two references I invoked (Nielsen & Shapiro, NAR 14:5936 (1986); Feinberg & Vogelstein, Anal. Biochem. 132:6–13 (1983)) come from secondary listings (the Unified Patents record for the parent and the Eberwine '545 background), not from the US 7,049,102 file wrapper. Treat their citation status as provisional.
- Citation-number artifacts reported literally. The patent's "Science 339:491," "Science 244:31–34," and "J. Biol. Chem. 262:1421–14249" are reproduced as they appear in the source text; the standard citations are 239:491–494, 244:331–334, and 262:14241–14249 respectively. I have not silently rewritten them.
- No PACER/PTAB file-wrapper review was performed for a reexamination or IPR that might have already decided these questions; such a record, if it exists, would supersede this analysis.
Generated 9/27/2026, 6:33:33 PM
Extensions
Patent term adjustments, term extensions, continuations, divisionals, family members, and expiration dates.
Derivative works
Defensive disclosure: derivative variations of each claim designed to render future incremental improvements obvious or non-novel.
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