Invalidity dossier

US 7067296

Methods and means for modulating PGE synthase activity

Current assignee: XR Communications, LLC (d/b/a Vivato Technologies)

Added 9/27/2026, 9:51:51 PM

At a glanceNo PTAB challenges1 lawsuit on fileasserted by XR Communications, LLC (d/b/a Vivato Technologies)Biotechnology

Active provider: DeepSeek · deepseek-v4-flash

Auto-generating section 1 of 2: Extensions…

Each section takes ~30-60s with web-search grounding. Keep this tab open — sections will fill in below as they complete.

Patent summary

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

✓ Generated

I'll search for authoritative information on US patent 7067296, including any 2026 litigation activity.

Let me pull the actual claim set and check for any 2026 litigation or PTAB activity specific to this patent.

Let me retrieve the actual claim text for US 7,067,296 specifically.

Search scope and caveats

I ran targeted searches against Google Patents, USPTO-linked sources, and CAFC 2026 materials. Two important caveats up front:

  1. The full patent text supplied to me is truncated before the claims section (it ends mid-way through the Experimental/Materials and Methods). I therefore could not verify the verbatim text of the granted claims of US 7,067,296 from the authoritative document. The claim summary below is reconstructed from the specification's stated aspects and must be treated as provisional, not authoritative.
  2. Number-match false positives. Searches for "7067296" repeatedly returned JP7067296B2 (Japanese patent, "Screening method for laminated ceramic electronic components" — multilayer ceramic capacitors) and shorthand references to "Sander '706" in unrelated seed-planter litigation. These are not US 7,067,296 and I excluded them.

Bibliographic summary — US 7,067,296 B2

Field Value
Title Methods and means for modulating PGE synthase activity
Patent number US 7,067,296 B2
Application number US 10/109,438
Filing date 2002-03-28
Issue (grant) date 2006-06-27
Priority date 1998-11-09 (US provisional 60/107,687)
Inventors Per-Johan Jakobsson; Bengt Samuelsson; Ralf Morgenstern; Anthony Ford-Hutchinson; Joseph Mancini
Assignee Karolinska Innovations AB (Stockholm, Sweden)
Status Expired – Lifetime; adjusted expiration 2021-08-17
Pre-grant publication US 2003/0064493 A1 (2003-04-03)
Main classification G01N 33/553; further A61P 19/02, 25/00, 25/28, 29/00, 35/00, 43/00; C12N 9/90; G01N 2500/04

Prosecution relationship (from the patent's own text): the specification states this application "is a divisional of U.S. patent application Ser. No. 09/433,466, filed Nov. 4, 1999, now U.S. Pat. No. 6,395,502," which claims priority under 35 U.S.C. §119(e) to U.S. Provisional Application 60/107,687 filed Nov. 9, 1998. Related family members visible in the record include US 7,192,733 B2 (from App. 10/962,155), US 7,645,601 B2 (from App. 11/679,585), and EP 1 129 188 B1 ("PGE synthase and methods and means for modulating its activity," WO 2000/028022).


Abstract (as published)

"Isolated PGE synthase, provided from encoding nucleic acid. Methods of production and use. Assays for modulators, especially inhibitors, of PGE synthase activity."


Plain-language overview of the claims

⚠️ Uncertainty flag: I was unable to retrieve the granted claim set of US 7,067,296. What follows is derived from the specification's enumerated "aspects of the invention," which are the likely claim bases. Do not rely on this as a verified claim chart.

The patent discloses three distinct assay concepts, expressed in the specification as:

  1. A binding/interaction assay — (a) bringing a PGE synthase polypeptide or peptide of the invention into contact with a putative binding molecule or other test substance; and (b) determining whether interaction/binding occurred. In plain terms: mix the enzyme (or a fragment) with a candidate compound and detect whether they stick to each other.

  2. A specific PGE-production assay — (a) incubating an isolated polypeptide having PGE synthase activity with a test compound in the presence of reduced glutathione and PGH₂ under conditions in which PGE is normally produced; and (b) determining PGE production. In plain terms: run the enzyme's natural reaction (PGH₂ → PGE₂, glutathione-dependent) with and without the candidate, and measure how much PGE₂ comes out.

  3. A generalized "cyclic endoperoxide" assay — (a) incubating an isolated polypeptide having PGE synthase activity with a test compound in the presence of a cyclic endoperoxide substrate, under conditions in which the enzyme normally converts that substrate to its 9-keto, 11α-hydroxy product; and (b) determining production of that product. The specification tabulates the contemplated substrate/product pairs: PGH₂→PGE₂, PGH₁→PGE₁, PGH₃→PGE₃, and PGG₂/PGG₁/PGG₃→their 15(S)-hydroperoxy PGE forms. In plain terms: a broader version of concept 2 that covers the enzyme's other endoperoxide substrates, not just PGH₂.

Since this is a divisional, its claims would be a subset of the parent disclosure — most likely the screening/assay method claims (concepts 2 and/or 3 above), with the polypeptide- and nucleic-acid-based claims more plausibly residing in the parent '502 or the sibling patents. Product detection is taught as HPLC, UV spectrometry, radioactivity detection, RIA, GC/MS, or TLC with radioactivity scanning. Inhibitors are identified by reduced product formation relative to a no-test-compound control.

Substantive background the claims sit on: the inventors identified human PGE synthase as the previously unannotated database sequences MGST1-L1 (GenBank AF027740) and PIG12 (GenBank AF010316), expressed it in E. coli, and measured ~0.25 µmol/min/mg glutathione-dependent activity in the membrane (not cytosolic) fraction — a microsomal, IL-1β-inducible enzyme.


2026 litigation / CAFC docket status

No 2026 (or any) CAFC or PTAB proceeding involving US 7,067,296 was found in my searches. Specifically:

  • Searches of CAFC 2026 oral-argument calendars, Rule 36 judgments, opinion releases, and 2026 Federal Circuit summaries returned no case captioned to US 7,067,296.
  • No IPR/PGR petition, PTAB hearing-schedule entry, or Federal Circuit appeal referencing this patent number appeared.
  • This is consistent with the patent's record: Google Patents lists it as "Expired – Lifetime," adjusted expiration 2021-08-17. A patent that expired in 2021 is unlikely to anchor a live 2026 infringement appeal, though expired patents can still appear in appeals over past damages — I found no such case.

I cannot state with high confidence that no such proceeding exists — my searches were web-based, and I did not directly query a complete Docket Navigator / PACER / PTAB API index. If you need a definitive negative, that requires an authoritative docket database query.


What I could not verify

  • The verbatim text and count of the granted claims of US 7,067,296 (readily available via USPTO Patent Public Search / PatentCenter for App. 10/109,438, or the patent PDF); the supplied document was truncated before the claims.
  • The exact independent/dependent claim breakdown and whether claim 1 is the binding assay, the PGH₂/glutathione assay, or the generalized endoperoxide assay.
  • Current ownership — "Karolinska Innovations AB" is listed as current assignee, but Google Patents disclaims having performed a legal analysis, and I did not retrieve the USPTO Assignment record for a post-issue chain of title.

If you can supply the claims section (or authorize a query against USPTO Patent Public Search for application 10/109,438), I can produce a verified, element-by-element claim summary.

Generated 9/27/2026, 10:13:44 PM

Cases on file (1)

Group view →

Specific litigation cases in our database that name US patent 7067296. The free-form analysis below may also discuss cases beyond this list.

Litigation summary

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

✓ Generated

I'll search for litigation involving US patent 7067296 across patent litigation sources.

Initial searches were noisy. Let me target patent litigation databases specifically.

No litigation results yet. Let me query litigation-specific databases directly.

Litigation Search Results — U.S. Patent No. 7,067,296

Bottom line

No litigation involving U.S. Patent No. 7,067,296 ("Methods and means for modulating PGE synthase activity," Karolinska Innovations AB) was identified. Within the sources I was able to query, there are no known district court, Federal Circuit, PTAB, or ITC proceedings asserting or challenging this specific patent.

I want to be explicit about the confidence level here: this is a negative finding based on the searches actually run, not an affirmative verification from a complete litigation database.

The patent as a litigation target

  • Patent No.: US 7,067,296 B2
  • Title: Methods and means for modulating PGE synthase activity
  • Assignee: Karolinska Innovations AB (original and current)
  • Inventors: Jakobsson, Samuelsson, Morgenstern, Ford-Hutchinson, Mancini
  • Filed: March 28, 2002 (App. No. 10/109,438) — divisional of Ser. No. 09/433,466 (now US 6,395,502)
  • Priority: November 9, 1998
  • Granted: June 27, 2006
  • Legal status (per Google Patents): Expired – Lifetime; adjusted expiration August 17, 2021
  • Continuation family: US 7,192,733 B2 and US 7,645,601 B2

The patent is a research-tool/biochemistry patent (assays for PGE synthase modulators) owned by a university technology-transfer entity, not a typical assertion vehicle. It expired in 2021, which independently makes active infringement litigation very unlikely today.

False positives encountered (excluded)

Searches for "7067296" returned several unrelated hits that are not this patent and should not be mistaken for it:

Hit What it actually is
JP 7067296 B2 Japanese patent to Murata Manufacturing — "Screening method for laminated ceramic electronic components" (multilayer ceramic capacitors)
AU 7067296 A Australian patent application — locomotive multiple-unit trainline/jumper for EP brake application
Case # 7067296 FDA Adverse Event Reporting System (FAERS) record for Mirena
7067296-59.2022.8.22.0001 Brazilian state court case number (TJRO), unrelated
Pranešimo Nr. 7067296 Lithuanian company-registry filing number

These share only the digit string and have no connection to US 7,067,296.

Sources queried

  • Google Patents page for US 7,067,296 B2 (fetched directly — the entry shows no litigation section; only classifications, family members, and an expiry-based legal status)
  • Unified Patents litigation/PTAB portal (via web search)
  • CourtListener / RECAP dockets (via web search)
  • General litigation-indexed web searches keyed to the exact number and to the related family patents (US 6,395,502; US 7,192,733; US 7,645,601)
  • Assignee-based searches (Karolinska Innovations AB)

Important caveats

  1. Tool limitation: I could not directly execute a docket query inside PACER, Unified Patents' portal, or CourtListener's API in this session; results came through general web search, which under-indexes patent dockets. A negative web-search result is not equivalent to a confirmed "no cases on file."
  2. Recommended verification before relying on this: run the patent number directly through (a) Unified Patents Portal → Litigation → Case List, (b) CourtListener/RECAP docket search, (c) Docket Navigator, and (d) USPTO Patent Center's "Litigation" tab for the patent. Any older, settled, or voluntarily dismissed case (common for research-tool patents) may not surface in general web search.
  3. Why a null result is plausible here: the patent expired August 17, 2021, is a divisional in a family that dates to a 1998 priority date, and is held by a non-practicing technology-transfer entity — a profile consistent with no enforcement history.

If you want, I can attempt a more targeted follow-up against a specific docket database syntax (e.g., a CourtListener or Docket Navigator query string) to try to convert this from "not found" to a confirmed null.

Generated 9/27/2026, 10:13:39 PM

Proceedings on file (0)

All PTAB activity →

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

Current assignee: XR Communications, LLC (d/b/a Vivato Technologies)

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

PTAB challenges

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

✓ Generated

I'll verify the structured block's "no proceedings" signal against live sources before reporting.

Proceedings overview

Zero AIA trial proceedings on file. The USPTO Open Data Portal returns no IPR, PGR, or CBM for US 7,067,296, and my independent searches of PTAB decision databases, CourtListener/Federal Circuit materials, and secondary PTAB coverage surfaced no petition, institution decision, FWD, or appeal naming this patent — so the breakdown is active: 0 / claims invalidated: 0 / claims sustained: 0 / settled: 0 / institution denied: 0.

Bottom line for a defendant: there is no PTAB record to lean on, but you almost certainly do not need one. This patent reached its adjusted expiration on 2021-08-17 and is docketed as "Expired – Lifetime." Any demand letter asserting it today can only reach pre-expiration conduct, and any validity challenge would be an academic exercise. The real defensive move is not an IPR — it is a damages-cutoff and standing analysis.


Proceedings by docket

None — no AIA trial proceeding exists on this patent

  • Type: N/A (no Inter Partes Review, Post-Grant Review, or Covered Business Method review identified)
  • Filed: N/A
  • Status: Verbatim from the structured source block: "The USPTO ODP API returns no AIA trial proceedings for this patent as of the most recent ingest." Plain-English gloss: no petition has ever been indexed for 7,067,296.
  • Judge panel: N/A — no panel was ever assigned.
  • Petition grounds: N/A — no claims were challenged under § 102, § 103, or § 112 in an AIA trial.
  • Institution decision: N/A — no institution deadline, oral hearing, or statutory one-year FWD deadline was ever triggered.
  • Final Written Decision: N/A — no claim of 7,067,296 has been canceled, confirmed, or construed by the Board.
  • Settlement / termination: N/A — there was nothing to settle or terminate.
  • Appeal: No PTAB FWD exists, so there is no CAFC appeal of a Board decision to report. I located no Federal Circuit opinion addressing this patent's validity, and I am not asserting one exists.
  • Defensive value: Because no IPR was ever filed, you get no § 315(e)(2) estoppel and no administrative invalidity record — but that cuts against you, not for you: it means every prior-art ground remains untested and unexhausted in any forum. The better lever is the patent's expired status, discussed below.

Strategic summary

Claim status — CANCELED vs. SUSTAINED vs. UNTESTED. All claims are UNTESTED. No IPR, PGR, or CBM ever reached this patent, so nothing has been canceled by the Board and nothing has been ratified by the Board. That is unusual for a patent of this profile: the underlying science (microsomal PGE synthase / mPGES-1, the "MGST1-L1"/"PIG12" sequence of GenBank AF027740 and AF010316) became one of the most heavily pursued anti-inflammatory drug targets of the 2000s, and the specification itself frames the discovery as "a potential novel drug target." A well-asserted patent on that target would ordinarily have drawn IPR petitions from branded pharma defendants. It apparently never did. The most probable explanations are (a) the claims were never asserted in a way that justified a $300K–$500K petition, (b) claim scope on an isolated-protein/assay patent made design-around easier than invalidation, and (c) the patent simply ran out its term before assertion pressure built. I cannot confirm which from the public record — treat this as the absence of a signal rather than affirmative evidence of weakness.

Estoppel landscape. With zero AIA trials, § 315(e)(2) estoppel is a null set — no petitioner and no privy is barred from anything. Practically, that means a defendant today retains the full menu of § 102/§ 103 grounds in district court and could theoretically file an IPR. But note the asymmetry: because the patent expired 2021-08-17, an IPR would be a pure cost exercise with no injunction to defeat. The binding constraint on a plaintiff is instead:

  • 35 U.S.C. § 286 — damages recoverable only for infringement within the six years preceding suit (i.e., roughly on or after 2020-09-27, given today's date), which is itself largely subsumed by the expiration date.
  • 35 U.S.C. § 287(a) — no pre-suit damages absent marking or actual notice, a frequent killer in expired-patent assertions.
  • No injunctive relief is available on an expired patent; the remedy is a past-damages royalty only.

Pattern signals. No repeated-petitioner pattern exists (no petitioner at all). No defensive aggregator such as Unified Patents appears in the chain — I found no Unified Patents, RPX, or similar filing against this patent. There is likewise no evidence of an aggressive PTAB-appeal posture by the patent owner, because the owner (Karolinska Innovations AB) never had a Board decision to appeal. Worth flagging for completeness: this patent is one member of a family — the application is a divisional of Ser. No. 09/433,466 (now US 6,395,502, priority 1998-11-09), with continuations issuing as US 7,192,733 and US 7,645,601. Those siblings carry the same 1998-11-09 priority and would run from the same 1999-11-04 non-provisional filing date, so they are expired or near-expired as well — but I have not verified their individual expiration dates, PTAB histories, or litigation histories, and you should confirm each before assuming symmetry.


Recommended next steps

  1. Do not build a defense around an IPR. There is nothing to distinguish, no institution record to attack, and no FWD to cite. The USPTO PTAB E2E docket search for this patent is the place to confirm the nil return yourself: https://ptab.uspto.gov/ (PTAB E2E / Patent Trial and Appeal Board End-to-End). I also found no Federal Circuit disposition to link; CourtListener's docket search is the cross-check: https://www.courtlistener.com/.

  2. Lead with expiration. Confirm the expiration date and any terminal disclaimers or maintenance-fee lapse on the face of the patent and in Patent Center (https://patentcenter.uspto.gov/). The Google Patents record lists Adjusted expiration 2021-08-17 / Status: Expired – Lifetime. If a demand letter is asserting this patent for ongoing activity, the assertion is defective on its face — respond with the expiration date and request withdrawal.

  3. If past conduct is being asserted, run the § 286/§ 287 math. Demand the plaintiff's damages period and its marking/notice theory. On an expired patent with no PTAB record and no injunctive exposure, the case usually compresses to a marking question and a pre-2020-09-27 cutoff.

  4. If a demand cites claims you can't match, say so explicitly. I cannot give you claim-level granularity here because no tribunal has ever construed these claims — there is no FWD, no institution decision, and no Board claim construction to quote. Do not let an adversary imply that Board proceedings have ratified the claims; the truthful statement is that no AIA trial has ever been instituted on 7,067,296, and no claim has been tested administratively. To obtain the actual claim text and count, pull the patent PDF from https://patents.google.com/patent/US7067296/en and read the claims section directly rather than relying on any secondary summary, including mine.

  5. Verify the siblings. Before responding, check US 6,395,502, US 7,192,733, and US 7,645,601 for PTAB history, expiration, and any district court assertions. My searches covered 7,067,296 specifically; the family's other members were not independently cleared.

Caveat on my own coverage: I could not complete a live, comprehensive sweep of every PTAB docket and CAFC docket for this patent number within this session, and the ODP ingest may lag recent filings. The structured source block's "no proceedings" default is consistent with everything I found, and I found no contradicting petition, FWD, settlement, or appeal — but a final confirmation against PTAB E2E is inexpensive and should be done before you rely on the nil result in a filing or a demand response.

Generated 9/27/2026, 10:14:02 PM

Ownership chain (2)

Asserters network →

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

  1. ? · reel 012585/0090 · Assignment

    Jakobsson, Per-Johan; Samuelsson, Bengt; Morgenstern, RalfKarolinska Innovations AB

    original chain of title

  2. ? · reel 015766/0689 · Assignment

    Ford-Hutchinson, Anthony; Mancini, JosephKarolinska Innovations AB

    chain completion

Assignment history

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

✓ Generated

I'll research the assignment chain for US 7,067,296. Let me run targeted searches against the USPTO Assignment Center and cross-reference sources.

Let me query the USPTO Assignment Center and related sources more directly.

Good — I'm finding assignment reel/frame data. Let me pull the Google Patents legal events and dig into those specific reels.

Assignment & Ownership Analysis — U.S. Patent No. 7,067,296

Scope note / tool limitation (read first): I was able to retrieve assignment reel/frame data from the Google Patents legal-events record for this family, but I could not directly execute a query against the USPTO Assignment Center or its API in this session, and the correspondent-of-record fields were not returned in any of the indexed records I recovered. Every reel/frame below is reported as it appears in the family's public legal-events data. Correspondents are marked "not retrieved" rather than guessed. This matters for signal #3 below.


Inventors

Inventor Residence / affiliation as recorded Employer at filing
Per-Johan Jakobsson Stockholm, SE — "MBB/Chemistry 2, Karolinska Institutet, S-171 77 Stockholm" Karolinska Institutet (Dept. of Medical Biochemistry & Biophysics)
Bengt Samuelsson Djursholm, SE — "MBB/Kemi 2, Karolinska Institutet" Karolinska Institutet (1982 Nobel laureate, prostaglandin biology)
Ralf Morgenstern Stockholm, SE — "IMM, Karolinska Institutet" Karolinska Institutet (Institute of Environmental Medicine)
Anthony Ford-Hutchinson Doylestown, PA, US Likely Merck Frosst (Kirkland, QC) — see caveat
Joseph Mancini "Kirkland" (per Justia listing for US 7,192,733) Likely Merck Frosst (Kirkland, QC) — see caveat

Caveat on the two North American inventors: My background knowledge is that Anthony Ford-Hutchinson was a long-time Merck Frosst Centre for Therapeutic Research scientist (Kirkland, Quebec) working on eicosanoid biology, and that Joseph Mancini was also Merck Frosst. I was not able to verify this in-session, so treat the Merck affiliation as likely, unverified. The residence data ("Doylestown, PA"; "Kirkland") is what the patent records themselves show.

Unusual patterns worth flagging:

  • Two-stage inventorship/assignment. Only three inventors (Jakobsson, Samuelsson, Morgenstern) appear in the parallel PCT/AU family record (AU 770307 B2, "Inventors/Applicants for US only"), whereas five inventors issue on the US patent. The two added inventors' assignments were executed 2002-02-05 to 2002-02-12 — i.e. roughly six weeks before the 2002-03-28 filing of divisional application 10/109,438 (which became US 7,067,296), and roughly 3 years after the original Swedish inventors assigned. This is a late-stage chain-of-title completion, not a departure pattern.
  • No evidence of inventor departure preceding the chain. There is no recorded indication that inventors left Karolinska Institutet; the three Swedish inventors remained academically affiliated, and the record shows no portfolio "fire-sale" follow-on.
  • Minor source discrepancy (flagged, not corrected): the OCR of US 6,395,502 renders the provisional as "filed Nov. 9, 1999," but the authoritative priority date is 1998-11-09 (Provisional 60/107,687). I treat the 1998 date as correct; the "1999" is an OCR artifact.

Original assignee

Karolinska Innovations AB (S-171 77 Stockholm, SE) — named as both original and current assignee on the issued patent.

  • Primary line of business: university technology-transfer / IP holding company for Karolinska Institutet (one of Europe's largest medical universities, and the institution of Bengt Samuelsson). It is a licensing-and-holding entity, not an operating company. It does not ship any product embodying the claims.
  • Product embodying the claims: None. The patent claims purified PGE synthase, encoding nucleic acids, and screening assays — research reagents/methods. There is no evidence Karolinska Innovations commercialized a product; its model is out-licensing to pharma.
  • Current status: No record of acquisition, dissolution, or bankruptcy surfaced. The patent's Google Patents legal status is Expired – Lifetime, adjusted expiration 2021-08-17, with no assignee change recorded across the ~15 years the patent was in force. (I could not independently confirm the present corporate status of Karolinska Innovations AB in this session — treat "still the owner of record at expiry" as well-supported, and any post-expiry corporate events as unverified.)

Assignment timeline

The records recovered all trace to the parent application (Ser. No. 09/433,466 → US 6,395,502) in the same family; US 7,067,296 is its divisional. I could not confirm that each reel was separately re-recorded against application 10/109,438.

  • 2000-01-21 → 2000-01-25 (executed) / recorded date not retrieved — Reel 012585/0090

    • Conveyance: Assignment
    • Assignor: Jakobsson, Per-Johan; Samuelsson, Bengt; Morgenstern, Ralf
    • Assignee: Karolinska Innovations AB (Sweden)
    • Correspondent: not retrieved (record as indexed shows only "ASSIGNMENT OF ASSIGNORS' INTEREST")
    • Context: Initial inventor-to-assignee assignment (original chain of title).
  • Reel 012747/0285 — content of this entry appeared in the family legal-events feed truncated; assignor/assignee/conveyance and dates were not recoverable.

    • Context: Unknown. Plausibly an inventor-addition or corrective/curative recording in the same window as 012585, but I will not assert this — flagged as an open item.
  • 2002-02-05 → 2002-02-12 (executed) / recorded date not retrieved — Reel 015766/0689

    • Conveyance: Assignment
    • Assignor: Ford-Hutchinson, Anthony; Mancini, Joseph
    • Assignee: Karolinska Innovations AB (per the family record; assignee field partially truncated)
    • Correspondent: not retrieved
    • Context: Late inventor assignment completing the chain — executed ~6 weeks before the divisional filing that matured into US 7,067,296.

No post-issuance assignments were found. There is no recorded transfer to any LLC, no security agreement, no merger, no change of name, and no license record in the indexed data. That is itself the finding: the original assignee (Karolinska Innovations AB) appears to have held the patent from issuance (2006-06-27) to expiry (2021-08-17).


Timeline diagram

timeline
    title Ownership of US 7067296
    1998 : Priority filing
    2000 : Swedish inventors assign to Karolinska Innovations
    2002 : US inventors assign to Karolinska Innovations
         : Divisional application filed
    2006 : Patent issued
    2021 : Patent expires

NPE / troll-pattern signals

# Signal Call Basis
1 Shell-entity transfer Not present No LLC/Inc. IP-holding vehicle ever appears. Chain begins and ends at Karolinska Innovations AB, a university TTO. No reel/frame shows a transfer to a "Holdings / Licensing / Ventures" entity.
2 Known asserter in the chain Not present No assignee matches Acacia, Marathon, IV, IPNav, Wi-LAN, Mosaid/Conversant, Vringo, Pendrell, Round Rock, MPHJ, Lumen View, Spangenberg entities, or any Unified/RPX high-frequency plaintiff. Assignee of record is the original university TTO (Reels 012585/0090; 015766/0689; current assignee per Google Patents = Karolinska Innovations AB).
3 Repeat correspondent across the chain Unclear The correspondent-of-record was not retrievable for any reel. I therefore cannot assess recurrence, and decline to infer it from the prosecuting firm (Dann, Dorfman, Herrell and Skillman / Kathleen D. Rigaut, which appears as attorney of record on the face of US 6,395,502 and US 7,645,601 — that is prosecution counsel, not the assignment correspondent).
4 Cascading transfers Not present Only inventor→assignee transfers exist; no consecutive LLC-to-LLC hops, and the two dated events are ~2 years apart (2000 → 2002), not <24 months of cascading transfers.
5 Pre-litigation transfer Not present The prior section found no litigation asserting this patent. The 2002 filing-window assignments predate issuance by ~4 years and are not keyed to any suit.
6 Bankruptcy fire-sale Not present No Chapter 7/11, no sale-in-proceedings record; Karolinska Innovations is not a distressed operating company.
7 Privateering Unclear / not evidenced The two North American inventors with apparent Merck Frosst ties assigning to Karolinska could in principle hint at a pharma–academic arrangement, but there is no recorded transfer from Karolinska to any asserting entity, no SEC disclosure, and no assertion activity — so no privateering finding can be supported.
8 Defensive aggregator (anti-NPE) Not present Chain does not terminate at RPX, AST, LOT, Unified, or OIN.

Verdict

Insufficient data — and, on the available record, non-asserting.

The only recorded conveyances are the two inventor-assignment groups to the original university assignee — Reel 012585/0090 (executed 2000-01-21→2000-01-25; Jakobsson/Samuelsson/Morgenstern) and Reel 015766/0689 (executed 2002-02-05→2002-02-12; Ford-Hutchinson/Mancini) — with no post-issuance transfer, no shell entity, no known asserter, and no litigation (consistent with the earlier litigation section). Because I could not confirm the correspondent fields and the Reel 012747/0285 entry was truncated, and because I could not query the Assignment Center directly, the honest verdict is Insufficient data, with the strong subsidiary observation that the chain terminates at the original TTO assignee and shows characteristic non-asserting university-licensing behavior, not NPE behavior.

Verify at: https://assignmentcenter.uspto.gov/ (search "7067296") and the mirrored indexing at https://assignment.uspto.gov/patent/index.html — specifically to (a) recover the correspondent of record on Reels 012585/0090, 012747/0285, and 015766/0689, (b) resolve the 012747/0285 entry, and (c) confirm whether Reels 012585/0090 and 015766/0689 were re-recorded against application 10/109,438 itself or only against parent 09/433,466. Those three items would move the verdict from "Insufficient data" to a confirmed null.


Cross-reference flags vs. the prior section

  • Consistent: inventors, assignee, family (US 7,192,733; US 7,645,601), filing/priority dates, and the no-litigation finding all agree with the earlier litigation section.
  • New (not in prior section): the concrete reel/frame numbers, the two-stage assignment timing (2000 vs. 2002), and the apparent Merck Frosst affiliation of two inventors.
  • Open item / potential gap in prior work: the earlier section did not surface any assignment data; this analysis adds it but leaves the 012747/0285 entry and all correspondent fields unresolved.

Generated 9/27/2026, 10:14:11 PM

Prior art

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

✓ Generated

I'll query multiple sources for US 7,067,296's citation record. Let me run these in parallel.

I have the key citation data. Let me now verify the front-page references specific to US 7,067,296 and try to retrieve its claim text.

Prior-Art Citation Analysis — US 7,067,296 B2

Scope note, date conflict, and confidence flag (read first)

Date conflict: My operating instructions state today's date is 2026-09-27; this task states Current Date: April 26, 2026. I'm flagging the discrepancy rather than silently picking one. It does not affect the substance below (the patent expired 2021-08-17), but you should resolve it.

Method/noise caveat: I could only run web search — not a direct API query against USPTO Patent Public Search, PatentCenter, or the Patent Assignment database. All "7067296" hits I relied on were filtered to the correct US document. Consistent with the prior sections, the searches again surfaced JP 7067296 B2 (Murata Manufacturing, multilayer ceramic capacitors) as a dominant false positive; excluded.

Verbatim-claims flag (unchanged from prior sections): I still could not retrieve the granted claim text of US 7,067,296. The authoritative text supplied ends mid-Experimental section. Therefore every "which claim(s) it anticipates" statement below is conditional on the provisional claim reconstruction from the prior section (binding assay; the PGH₂/glutathione PGE-production assay; the generalized cyclic-endoperoxide assay). Treat the § 102 mapping as analytical reasoning, not a verified claim chart.


Ground truth located: the "References Cited" record

US 7,067,296 is a divisional of US 6,395,502 B1 (App. 09/433,466; filed Nov. 4, 1999), and its disclosure is identical. I retrieved the front-page "(56) References Cited" list from the parent and from the sibling in the same family, which mirror each other:

Notable structural finding: the front page contains no "U.S. Patent Documents" section at all — zero U.S. patent citations. It lists exactly one foreign patent document and a set of non-patent publications. I could not directly read the '296 front page, so I state the list as "inherited from the parent and mirrored in the sibling"; a divisional examiner occasionally adds art, so verify against the '296 PDF.

Table 1 — Cited prior art (as listed on US 6,395,502 / US 7,645,601)

# Full citation Date Type
P1 WO 99/14356 published March 1999 Foreign patent doc
N1 Polyak, Kornelia, et al., "A model for p53-induced apoptosis," Letters to Nature 389:300–305 Sep. 18, 1997 Journal
N2 Shalinsky, D.R., et al., "Inhibition of GSH-dependent PGH2 isomerase in mammary adenocarcinoma cells by allicin," Prostaglandins 37(1):135–48 (PubMed abstract) Jan. 1989 Journal
N3 Ogorochi, Toshiya, et al., "Purification and Properties of Prostaglandin H-E Isomerase from the Cytosol of Human Brain: Identification as Anionic Forms of Glutathione S-Transferase," J. Neurochem. 48:900–909 1987 Journal
N4 Tanaka, Yasuhito, et al., "Immunochemical and Kinetic Evidence for Two Different Prostaglandin H-Prostaglandin E Isomerase in Sheep Vesicular Gland Microsomes," J. Biol. Chem. 262:1374–1381 Jan. 25, 1987 Journal
N5 Watanabe, Kikuko, et al., "Two Types of Microsomal Prostaglandin E Synthase: Glutathione-Dependent and -Independent Prostaglandin E Synthases," Biochem. Biophys. Res. Commun. 235:148–152 1997 Journal
N6 Jakobsson, Per-Johan, et al., "Identification of Human prostaglandin E synthase: A microsomal, glutathione-dependent, inducible enzyme, constituting a potential novel drug target," Proc. Natl. Acad. Sci. 96:7220–7225 June 1999 Journal (inventors' own)
N7 XP-002132552 — EMBL/GenBank/DDBJ Database, Accession No. AF027740 ("MGST1-L1") created Nov. 1997 (listed "Jul. 5, 1999" in '502) Sequence database entry

Critical-date framework (pre-AIA, since priority is 1998)

  • Priority date: Nov. 9, 1998 (provisional 60/107,687)
  • Parent filing: Nov. 4, 1999 → § 102(b) statutory-bar critical date ≈ Nov. 4, 1998
  • The '296 divisional takes the parent's filing date for § 102(b) purposes (proper divisional), so the operative bar date is Nov. 4, 1998.

This is decisive for the mapping below: references published before Nov. 9, 1998 are § 102(a)/(b) art; references published after Nov. 9, 1998 but before the filing date can only be § 102(a)/(e) art — and if they are the inventors' own work, they are neither "by others" (§ 102(a)) nor a § 102(b) bar (inside the one-year grace period).


§ 102 analysis, reference by reference

P1 — WO 99/14356 (published March 1999)

  • Full citation: PCT international publication WO 99/14356, published March 1999.
  • Date: published after the Nov. 9, 1998 priority date → cannot be § 102(b) art; only § 102(a)/(e).
  • Description / § 102 mapping: ❗ I could not retrieve the content of WO 99/14356 in this session. It appears in the citations as a "D"-type reference (cited in the application). Because it post-dates the priority date, it would be relevant only as § 102(e)-type art if it designates the US and pre-dates the applicant's actual filing — a narrow window. I will not speculate on its disclosure. Verify this reference directly before relying on any anticipation conclusion involving it.

N1 — Polyak et al. 1997 (Nature 389:300–305)

  • Date: Sep. 18, 1997 → pre-priority; § 102(a)/(b) art.
  • Description: Reports the cloning of p53-upregulated sequences including "PIG12," described as "a novel member of the microsomal glutathione S-transferase family of genes." It discloses the sequence (GenBank AF010316) but assigns no enzymatic function — no suggestion it is PGE synthase.
  • Potential § 102 anticipation: Relevant only if the divisional contains a claim to the isolated nucleic acid of that sequence (or a fragment/probe). Such a claim could be anticipated by the printed disclosure of the sequence. Against the assay-method claims (the likely subject matter of this divisional), N1 does not anticipate — a reference disclosing a sequence with no known function cannot anticipate a method of screening for modulators of PGE synthase activity, because the recited "PGE synthase activity" element would be absent.

N2 — Shalinsky et al. 1989 (Prostaglandins 37(1):135–48)

  • Date: Jan. 1989 → § 102(b) statutory bar.
  • Description: "Inhibition of GSH-dependent PGH2 isomerase in mammary adenocarcinoma cells by allicin" — i.e., using a glutathione-dependent PGH₂→PGE₂ isomerase activity as a target and measuring inhibition by a test substance (allicin) in a cellular context.
  • Potential § 102 anticipation: This is the closest cited art to a generic "screening method" claim. It discloses the essential logic — contact a GSH-dependent PGH₂ isomerase with a substance and measure reduced PGE₂ formation. It could anticipate a broad assay claim that does not require an isolated/purified/recombinant enzyme (e.g., one practiced on a cell or a crude preparation). It would not anticipate a claim reciting "an isolated polypeptide which has PGE synthase activity" of SEQ ID NO:2 (or recombinant human enzyme), because the reference's activity is attributable to a cellular preparation and the specific human enzyme was unidentified. Anticipation turns entirely on how the claim's enzyme element is worded — exactly the wording I could not verify.

N3 — Ogorochi et al. 1987 (J. Neurochem. 48:900–909)

  • Date: 1987 → § 102(b).
  • Description: Purifies PGH-E isomerase from human brain cytosol, identifying it as anionic forms of glutathione S-transferase — a cytosolic, GST-type PGE-forming activity.
  • Potential § 102 anticipation: Discloses a human PGE-forming enzyme and its glutathione dependence. But it characterizes a cytosolic/GST enzyme, whereas the patent's invention is the microsomal, IL-1β-inducible 15 kDa enzyme (SEQ ID NO:2). It therefore does not anticipate claims requiring that enzyme; at most it is § 103 background or a § 102 reference against an over-broad genus claim to "a PGE synthase."

N4 — Tanaka et al. 1987 (JBC 262:1374–1381)

  • Date: Jan. 25, 1987 → § 102(b).
  • Description: Immunochemical/kinetic evidence for two different PGH→PGE isomerases in sheep vesicular gland microsomes; the 17.5 kDa protein had a K_m for PGH₂ of 40 µM; both were glutathione-dependent and lacked GST activity.
  • Potential § 102 anticipation: Discloses microsomal, glutathione-dependent PGE synthase activity with a defined K_m — methodologically very close to the assay the patent teaches. But it concerns ovine protein, was not purified to homogeneity, and the inventors expressly relied on this reference as showing the prior art lacked a pure enzyme. It could anticipate a claim to a method of assaying microsomal PGE synthase activity generically; it does not anticipate claims tied to the human recombinant enzyme.

N5 — Watanabe et al. 1997 (BBRC 235:148–152)

  • Date: 1997 → § 102(b).
  • Description: Demonstrates two types of microsomal PGE synthase (glutathione-dependent and -independent) across rat organs; high GSH-dependent activity in ductus deferens, genital accessory organs and kidney.
  • Potential § 102 anticipation: Establishes the glutathione-dependent vs. -independent dichotomy recited throughout the specification. Relevant to § 102(a)/(b) against any claim not limited to a specific enzyme molecule; but, like N4, it discloses activity in tissue preparations, not an isolated/recombinant human PGE synthase, so it does not anticipate assays requiring the isolated polypeptide.

N6 — Jakobsson et al. 1999 (PNAS 96:7220–7225) ⚠️ key nuance

  • Date: June 1999 → after the Nov. 9, 1998 priority date, but before the Nov. 4, 1999 parent filing.
  • Description: The inventors' own paper identifying human microsomal, glutathione-dependent, IL-1β-inducible PGE synthase — i.e., the disclosure of the invention itself.
  • Potential § 102 anticipation: NONE. This is the pivotal legal point most likely to be mishandled:
    • It is not § 102(b) art: publication (June 1999) is within one year of the Nov. 4, 1999 parent filing, so the statutory bar does not attach.
    • It is not § 102(a) art: it is the work of the inventors themselves, hence not "known or used by others."
    • It is not § 102(e) art: not a U.S. patent or published U.S. application.
    • It is cited for disclosure duty / background, functionally a "D" reference — not an anticipatory reference.
    • Only if the applicant were unable to claim the Nov. 9, 1998 priority date would its status change — and there is a provisional supporting that date.

N7 — GenBank AF027740 (XP-002132552, "MGST1-L1")

  • Date: entry created Nov. 1997 (front page of '502 lists "Jul. 5, 1999").
  • Description: The sequence record for the cDNA now shown to encode human PGE synthase — deposited under a microsomal glutathione S-transferase name, with no enzymatic function ascribed.
  • Potential § 102 anticipation: If the Nov. 1997 creation date is the operative public-availability date, this is pre-priority, § 102(a)/(b) art. It anticipates only product claims to the isolated polynucleotide/polypeptide of that sequence (a public database sequence can anticipate a claim to that sequence if the claim is so drawn). It does not anticipate the assay-method claims, because a sequence deposited without functional annotation does not disclose PGE synthase activity, and the specification itself emphasizes that "no function has previously been ascribed to these cDNA sequences." Note the same reasoning applies to the companion record AF010316 (PIG12), which is discussed in the specification but does not appear in the front-page "References Cited" list.

Consolidated § 102 conclusion

Reference § 102 category Claims potentially anticipated (conditional) Confidence
WO 99/14356 § 102(a)/(e) only (post-priority) Unknown — content not retrieved Very low
Polyak 1997 § 102(a)/(b) Isolated-nucleic-acid product claims (if any) Moderate (product claims only)
Shalinsky 1989 § 102(b) Broad assay claim not requiring isolated enzyme Moderate (turns on claim wording)
Ogorochi 1987 § 102(b) Genus-level "PGE synthase" claims only Low
Tanaka 1987 § 102(b) Generic microsomal-activity assay claims Low–Moderate
Watanabe 1997 § 102(b) Generic GSH-dependent activity claims Low
Jakobsson 1999 Not prior art None (inventors' own grace-period publication) High
AF027740 (MGST1-L1) § 102(a)/(b) Isolated sequence product claims (if any) Moderate (product claims only)

Bottom line: On the reconstructed claim set (screening/assay methods using an isolated PGE synthase polypeptide), none of the cited references appears to squarely anticipate under § 102. Each cited reference lacks at least one element — either the isolated/recombinant human enzyme, or the recognition that the MGST1-L1/PIG12 sequence is PGE synthase. The strongest § 102 candidate is Shalinsky 1989, and only against a claim drafted broadly enough to cover a non-isolated GSH-dependent PGH₂ isomerase reaction. The strongest references against product claims are the sequence disclosures (Polyak 1997 / AF027740). The one reference that literally discloses the invention — Jakobsson 1999 — is legally excluded as the inventors' own pre-filing publication within the grace period, which is presumably why the applicant's priority chain (provisional 60/107,687 → parent 09/433,466) matters so much here.


What I could not verify (recommended before you rely on this)

  1. Verbatim claims of US 7,067,296 — still not obtained; the claim-conditioned mapping above is provisional. Confirm via USPTO Patent Public Search / PatentCenter for App. 10/109,438, or the patent PDF.
  2. The front-page "(56)" list as printed on US 7,067,296 itself — I used the parent '502 and sibling '601 lists. Divisional examiners sometimes add references; compare against the '296 front page.
  3. The content and date of WO 99/14356 — not retrieved; it materially affects the § 102(a)/(e) analysis because it post-dates the priority date.
  4. Actual deposition/public-availability date of GenBank AF027740 — "created Nov. 1997" vs. the "Jul. 5, 1999" listing; this changes whether N7 is § 102(a)/(b) or post-priority art.
  5. A definitive USPTO database pull — my tools were web-search only; a direct PatentCenter query is needed to convert these findings from "web-verified" to "database-verified."

If you can provide the claims section of US 7,067,296 (or authorize a PatentCenter pull), I can convert the conditional § 102 table into a verified, element-by-element claim chart.

Generated 9/27/2026, 10:14:33 PM

Obviousness

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

✓ Generated

I'll pull the authoritative claim set and the prior-art citations cited on the patent's face, since the supplied text truncates before the claims.

Let me try to retrieve the granted claim text specifically for this patent.

Let me make one final attempt at the exact granted claims for US 7,067,296 and any record of an obviousness rejection in its file history.

Obviousness Analysis — U.S. Patent No. 7,067,296

35 U.S.C. § 103(a) (pre-AIA)


0. Flagged corrections/inconsistencies with the earlier sections

Before the substance, two cross-reference flags (per the build-on-don't-repeat rule):

  1. New proxy claims recovered. My earlier section stated the granted claims of US 7,067,296 could not be verified. That remains true, but I did recover two family proxies that materially improve the analysis: (i) the parent's claim 1 (US 6,395,502 B1, "What is claimed is: 1. An assay method for identifying a modulator of Prostaglandin endoperoxidase (PGE) synthase activity, which method comprises: (a) incubating an isolated polypeptide selected from the group consisting of: a polypeptide which comprises the amino acid sequence of SEQ ID NO. 2…" — https://patentimages.storage.googleapis.com/f0/c2/db/cfb894ead9970b/US6395502.pdf), and (ii) the Canadian sibling CA 2349529 C claim 11 (membrane-fraction inhibitor-identification method) and claims 14–20 (methods of producing a PGE synthase polypeptide by recombinant expression plus activity testing) — https://patents.google.com/patent/CA2349529C/en. These are proxies, not the '296 claims.

  2. A contradiction with the earlier section's hypothesis. My earlier "plain-language overview" predicted the '296 divisional claims would most likely be the PGH₂/glutathione screening assay (concept 2) and/or the generalized cyclic-endoperoxide assay (concept 3). That prediction is now in tension with the recovered parent proxy: the parent's claim 1 already appears to be an assay method for identifying a modulator using an isolated polypeptide comprising SEQ ID NO: 2. Because a divisional cannot re-claim the parent's invention, the '296 claims more plausibly lie elsewhere in the same disclosure — e.g., the cyclic-endoperoxide-generic assay, the membrane-fraction assay, the method-of-production claims, or nucleic-acid/host-cell claims. I cannot resolve this without the '296 claim set, so the analysis below is run against all plausible claim types, clearly labeled.


1. Legal framework and the "Prior Art section" actually supplied

  • Governing law: Effective filing date is pre-March 16, 2013 (priority 1998-11-09; application filed 2002-03-28). Pre-AIA § 103(a) applies, with the Graham v. John Deere factors (scope/content of prior art; differences; PHOSITA level; secondary considerations), as glossed by KSR Int'l v. Teleflex (2007) (a claimed combination is obvious where prior-art elements are arranged as taught/obvious, and "obvious to try" suffices where the field presents a finite number of identified, predictable solutions).
  • What the supplied "Prior Art section" contains: prior-art keywords pge, pge synthase, synthase, polypeptide, activity; prior-art date 1998-11-09; and the specification's own background recitation. There is no separate cited-reference list in the supplied text. I therefore ground the analysis in (a) the references the patent itself characterizes as prior art, and (b) the public database entries the patent admits pre-existed (GenBank AF027740, AF010316).
  • Important procedural note: the patentee's own PNAS article (Jakobsson et al., PNAS 96:7220–7225, June 1999) and PCT publication WO 00/28022 (18 May 2000) post-date 1998-11-09 and are not § 102 prior art against the priority date. Any obviousness case must be built on pre-November-1998 art.

2. Person Having Ordinary Skill in the Art (PHOSITA)

A Ph.D.-level biochemist or molecular biologist (or M.S. with several years' experience) with working knowledge of: (i) eicosanoid/prostaglandin biochemistry (COX → PGH₂ → PGE₂); (ii) standard recombinant DNA and heterologous expression (Sambrook, Molecular Cloning, 2d ed. 1989 — cited by the patent itself); and (iii) routine enzyme-activity assays with chromatographic/radioactive detection.


3. The claim elements (decomposed, per proxy claim type)

Proxy claim Limitations
'502 cl. 1 (assay/modulator) (a) incubate an isolated polypeptide comprising SEQ ID NO: 2 [or a portion] and a test substance; (b) determine PGE production
CA '529 cl. 11 (membrane-fraction inhibitor ID) (a) membrane fraction from cells recombinantly producing PGE synthase; (b) incubate ± test compound with a cyclic endoperoxide substrate; (c) detect reduced product → inhibitor
CA '529 cl. 12 same, with reduced glutathione + PGH₂, measuring PGE
CA '529 cls. 14–20 (production) recombinantly express nucleic acid encoding PGE synthase; test the polypeptide for PGE synthase activity (cl. 18: incubate with PGH₂ + reduced glutathione, measure PGE)
CA '529 cls. 21–27 (nucleic acid construct / host cell) nucleotide sequence encoding SEQ ID NO: 2 operably linked to regulatory sequences; host cell transformed therewith

Note the literal term used in the parent claim is "Prostaglandin endoperoxidase (PGE) synthase" — I preserve that wording.


4. Prior art references (all pre-November 1998 unless noted)

Reference Teaching
Ogino et al. (1977) JBC 252:890-5 Microsomal PGE synthase can be solubilized and partly purified from bovine/ovine seminal vesicles; assay format = microsomes + PGH₂, measure PGE.
Moonen et al. (1982) Methods Enzymol 86:84-91 Standard microsomal PGE synthase preparation/assay; Km(PGH₂) ≈ 40 µM.
Tanaka et al. (1987) JBC 262:1374-81 Two mAbs immunoprecipitate a 17.5 kDa glutathione (GSH)-dependent PGE synthase with no glutathione S-transferase activity.
Watanabe et al. (1997) BBRC 235:148-52 GSH-dependent microsomal PGE synthase activity across rat organs (ductus deferens, genital accessory organs, kidney).
Burgess & Reddy (1997) Biochem Mol Biol Int 41:217-26 A 16.5 kDa microsomal GSH-dependent PG endoperoxide-metabolizing protein (not accepting classical GST substrates).
Urade et al. (1995) J Lipid Med 12:257-73 GSH-transferase superfamily proteins possess PGE/PGD/PGF synthase activities.
Smith (1997) Adv Exp Med Biol 400B:989-1011 Reviews the prostanoid enzymes; notes PGE formation "has not been attributed to a unique protein."
Polyak et al. (1997) Nature 389:300-305 Clones p53-induced PIG12, "a novel member of the microsomal glutathione S-transferase family of genes." No function ascribed.
GenBank AF027740 ("MGST1-L1") / AF010316 ("PIG12"), EST R76492 — deposited 1997 Full nucleotide and predicted amino-acid sequences publicly available; annotated as MGST-family members.
Andersson et al. (1994) Biochim Biophys Acta 1204:298-304 aa 1-41 removable from MGST1 by proteolysis without loss of function.
Lam et al. (1997) JBC 272:13923-28 C-terminal segments exchangeable between LTC₄ synthase and FLAP without loss of function.
Naraba et al. (1998) J Immunol 160:2974-82; Matsumoto et al. (1997) BBRC 230:110-4; Huang et al. (1998) Cancer Res 58:1208-16; Mitchell et al. (1994) Br J Pharmacol 113:1008-14 COX-2 and inducible PGE synthase are co-induced by IL-1β/LPS; A549 cells as the model system.

5. The obviousness combinations

Combination A — Primary: "Known assay" + "Known sequence" + "Routine recombinant expression"

References: Ogino/Moonen/Watanabe (PGE synthase assay using microsomes + PGH₂ + GSH, measuring PGE) in view of Polyak 1997 / GenBank AF027740 & AF010316 (sequences publicly available) in further view of Sambrook (routine cloning/expression).

Motivation, articulated:

  • The art already possessed a complete functional assay for PGE synthase (PGH₂ + reduced GSH → PGE₂, detected chromatographically/RIA). Nothing new was needed on the detection side.
  • The art expressly recognized that native purification was the bottleneck: microsomal PGE synthase "rapidly inactivated during the course of purification," was a membrane protein, and was present at very low cellular abundance. The recognized problem — obtaining a stable, homogeneous source of enzyme suitable for drug screening — would have directed a POSITA to recombinant expression.
  • The sequences were in hand (deposited 1997); expressing a cloned cDNA in E. coli and testing it for enzymatic activity was routine and predictable (the patent's own vector, pSP19T7LT, comes from Weinander et al. (1995) Biochem J 311:861-6 — pre-1998).
  • Result: a POSITA would have had a reasonable expectation of success in making a recombinant MGST1-L1/PIG12 polypeptide and running the known PGE synthase assay on it.

Supports: the assay claims (proxy '502 cl. 1; CA '529 cls. 11–12) and the production-method claims (CA '529 cls. 14–20), because those claims recite known assay steps applied to a known, cloned sequence.

Combination B — "Family-member screen" (the strongest KSR "obvious to try" case)

References: Tanaka 1987 (microsomal PGE synthase is ~17.5 kDa, GSH-dependent, membrane-bound, with no GST activity) + Burgess & Reddy 1997 + Urade 1995 in view of the MGST1/LTC₄-synthase/FLAP/MGST2/MGST3 family (Andersson 1994; Lam 1997) in view of Polyak 1997 / GenBank (MGST1-L1, PIG12).

Motivation:

  • By 1997 the art had a small, finite, structurally related set of ~14–18 kDa membrane-associated eicosanoid/GSH-metabolizing proteins (the family later formalized as MAPEG). Polyak itself flagged PIG12 as a new member of that family.
  • A POSITA seeking the microsomal PGE synthase would rationally test the newly identified family members — a member of the same superfamily as a GST with GSH-dependent peroxidative chemistry is an obvious candidate for a GSH-dependent endoperoxide isomerase.
  • Under KSR, where the field presents "a finite number of identified, predictable solutions," pursuing this family is "obvious to try" and yields the anticipated result.

Supports: all assay/production claim types; also relevant to any claim whose only distinguishing feature is the identity of the enzyme used.

Combination C — Assay-format and model-system limitations (dependent-style limitations)

  • Detection modalities (HPLC, UV at 195 nm, RIA, TLC/radioactivity scanning, GC/MS) are each conventional alternatives expressly catalogued in the art and disclosed by the patent as mere choices — obvious per KSR ("a court must ask whether the improvement is more than the predictable use of prior art elements according to their established functions").
  • A549 / IL-1β model is squarely prior art (Huang 1998; Mitchell 1994; Matsumoto 1997; Naraba 1998), so claims reciting a cell-based or membrane-fraction coarse screen are supported by art that already used IL-1β-stimulated A549 cells to study COX-2 and PGE₂ output.
  • The IL-1β→PGE synthase induction finding itself is arguably an inherent property of the enzyme; the art already taught co-induction of COX-2 and inducible PGE synthase activity (Naraba 1998).

Combination D — For nucleic-acid-construct / host-cell claims (if the '296 includes them)

Recombinant constructs and transformed hosts are the routine, predictable consequence of Combination A; nothing in such claims distinguishes them from standard molecular-biology practice (Sambrook 1989).


6. Rebuttal-side considerations (what cuts against obviousness)

  1. The art affirmatively said the answer was unknown. Urade 1995: "little is known about the properties of PGE synthase"; Smith 1997: "The PGE synthase story has been a perplexing one," with PGE formation "not attributed to a unique protein." This is genuine evidence against a certainty of success and is the patentee's best teaching-away/§103-defeating material.
  2. The database sequences had no ascribed function. Polyak 1997 characterized PIG12 purely as an MGST-family gene; neither reference suggested PGE synthase. The point of novelty is the function discovery, not any assay step.
  3. Under pre-AIA §102, these same database entries are arguably § 102(b) printed publications — but that is an anticipation argument for composition claims to SEQ ID NO: 2 (and the "isolated form" question under In re Baxter Travenol), not a §103 argument for the assay/production methods, because no prior art taught performing the PGE synthase reaction on that protein.
  4. Deuel-type caution: In re Deuel (Fed. Cir. 1995) held that a known protein plus generic cloning methods does not automatically render a specific DNA sequence obvious. Its force here is limited because the sequences were already disclosed; the "cloning" step is gone, leaving only "express and assay."

7. Claim-limitation conclusions (provisional)

Claim type (proxy) §103 assessment Confidence
Assay for modulator using polypeptide comprising SEQ ID NO: 2 ('502 cl. 1-type) Prima facie obvious — Combination A/B; all steps known, only the enzyme source is new, and that source was a publicly deposited sequence Moderate-high if the flux of the argument is that the sequence was known
Membrane-fraction inhibitor ID with cyclic endoperoxide substrate (CA '529 cl. 11–12) Prima facie obvious — Ogino/Moonen/Watanabe teach the substrate/GSH/detection; membrane-fraction format is standard Moderate-high
Method of producing PGE synthase polypeptide + testing activity (CA '529 cls. 14–20) Prima facie obvious — routine expression + known assay High
Nucleic-acid construct / host cell (CA '529 cls. 21–27) Prima facie obvious as a routine consequence; but if claim recites SEQ ID NO: 1 per se, the analysis collapses to §102 (GenBank publication) Moderate
Any claim reciting the discovery that MGST1-L1/PIG12 is PGE synthase as the point of novelty Weak §103 case — the prior art uniformly failed to identify the function; the field had not converged on this protein Low (patentable)

Net: the strongest § 103(a) case is against the method/assay and production claims, built as: Ogino/Moonen/Watanabe (known PGE synthase reaction and assay) + Polyak/GenBank AF027740 & AF010316 (publicly available sequences) + routine recombinant-expression and detection techniques, with Tanaka 1987/Urade 1995/Burgess & Reddy 1997 supplying the structural/functional family cue that made the newly deposited MGST-family members obvious candidates to screen. The weakest case is against any claim whose inventive weight rests on recognizing the function of these sequences.


8. What I could not verify (reminder, unchanged)

  • The verbatim granted claims of US 7,067,296 and their independent/dependent structure. Everything above is keyed to proxy claims (parent US 6,395,502 cl. 1; CA 2349529 C cls. 11–20) and must be re-run against the actual '296 claim set from USPTO Patent Public Search (App. 10/109,438) or the granted PDF before being relied upon.
  • Any examiner-cited art and rejections in the '296 file wrapper (the search tool returned no file-history documents for the '296; the "no separate citation list" observation in §1 is a limitation of the supplied page, not a statement that none exists).
  • Two OCR noise artifacts in the parent PDF ("MOST1-L1"/"MOST1" for MGST1-L1/MGST1; "endoperoxidase" in claim 1) are reproduced above literally and not auto-corrected, per the strict-identifier rule.

If you authorize a direct USPTO Patent Public Search / PatentCenter pull for application 10/109,438, I can convert § 7 from a proxy-based assessment into a verified, element-by-element claim chart.

Generated 9/27/2026, 10:14:55 PM

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Derivative works

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1 tracked lawsuit name US 7067296.