US 11402389

I'll run targeted searches for this exact patent number, including litigation/docket checks.

Let me get the issued claim text and check for any litigation or PTAB activity tied to this exact number.

Bottom line

I found authoritative records for US 11,402,389 B2 matching the number exactly. I found no evidence of any litigation, CAFC appeal, or PTAB proceeding involving this patent. Details and the honest limits of what I could verify are below.

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Bibliographic summary (from the patent's own front‑page/Google Patents record)

Source: https://patents.google.com/patent/US11402389/en

Abstract (as published): "The present invention relates generally to the field of implant related risk of revision, in particular implant related risk of revision not caused by an infection or metal on metal reaction. The present invention provides methods of diagnosing implant related risk of revision, use of kits for such diagnostic purposes and compositions for use in the treatment of implant related risk of revision, in particular implant related risk of revision not caused by an infection or metal on metal reaction."

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Plain‑language overview of the claims

Important caveat on claim text. The authoritative full text I was given contains the abstract and description but not the granted claims section, and I was unable to retrieve the verbatim issued claim set of US 11,402,389 B2 within my tool limits. What follows is derived from (a) the specification's stated "aspects," which track the claim structure, and (b) the claim language of the close family members the search surfaced. Treat the exact wording/numbering as not verified.

The specification sets out three claim aspects:

1. First aspect – diagnostic method (believed to be independent claim 1). A method of diagnosing "implant related risk of revision" comprising providing a biological sample from a subject with an implant and detecting the level of at least one polypeptide selected from calprotectin, S100A8 and S100A9, wherein the biological sample is synovial fluid (preferably synovial fluid from the implant site). The diagnosis rests on threshold values: <4 mg/L = no risk / stable implant**; **≥4 mg/L = risk of revision**. The claim family also covers **staging**: **4–50 mg/L = "pathology initiation"** (early loosening — aseptic loosening, dislocation, osteolysis) versus **>50 mg/L = "acute pathology" (implant‑associated infection, metal‑on‑metal reaction). Value thresholds are expressly tied to measurement by the CALPROLAB™ Calprotectin ELISA (ALP) kit.

   • A recurring limitation across the family: the detected polypeptide must be secreted, not intracellular content of intact cells in the sample — i.e., the sample must not be treated in a way that lyses cells.

2. Second aspect – use of a kit. Use of a kit for diagnosing implant‑related risk of revision in a subject with an implant, the kit being suitable for detecting calprotectin/S100A8/S100A9 in a synovial fluid sample, preferably an ELISA kit (solid support coated with monoclonal antibodies; enzyme‑labelled polyclonal conjugate, preferably alkaline phosphatase; p‑nitrophenyl phosphate substrate), or a lateral‑flow immunochromatographic kit.

3. Third aspect – composition for use in treatment. A composition for use in treating a subject diagnosed by the method of claim 1, comprising an anti‑osteolytic agent and/or an anti‑phlogistic/anti‑inflammatory agent (e.g., bisphosphonates, NSAIDs, acetaminophen, diclofenac, cortisone, etc.), with embodiments directed to asymptomatic subjects and to subjects not having acute pathology, implant‑associated infection, or metal‑on‑metal reaction.

For reference, the closest verbatim independent‑claim language I could actually retrieve is from the pre‑grant publication US 2019/0361035 A1 (claims 49 and 57), which recites: detecting calprotectin/S100A8/S100A9 in a synovial‑fluid sample from a subject with an implant and comparing to a control, with "a level ≥4 mg/l … indicative of a diagnosis of implant related risk of revision," and the polypeptide being "a secreted polypeptide and not intracellular polypeptide of intact cells." See https://patents.justia.com/patent/20190361035

Note also that a separate, later‑issued family member, US 12,146,885 (claims available at https://patents.justia.com/patent/[12146885](/patent/12146885)), recasts the same disclosure as treatment claims (administer anti‑inflammatory drug therapy at 4–50 mg/L, or joint surgery at ≥50 mg/L). That is a different patent number and should not be attributed to US 11,402,389.

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Litigation / CAFC 2026 check

• No litigation, CAFC appeal, or PTAB proceeding involving US 11,402,389 was found.
• Every "’389" hit returned by my searches refers to a different patent: e.g., U.S. 6,233,389 (TiVo/DISH), 10,306,389 (Solos Technology v. Meta), and various unrelated "’389" designations. None is US 11,402,389, and I have not conflated them.
• One search returned a hit for the string "11402389" against a UK Companies House filing (company no. 11402389, "Baby Mineral Limited") — plainly unrelated to the patent.

Limits on this check: I searched via general web search, not by direct PACER/CourtListener docket or USPTO PatentCenter/PTAB API query. The absence of results is therefore strong but not conclusive negative evidence for 2026 activity; the most recent grant‑date‑adjacent records I could confirm are the 2022‑08‑02 issue and the 2022‑08‑23 assignment to Lyfstone B.V.

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Confidence flags

• High confidence: patent number, title, application number, filing/priority/issue dates, inventors, assignee history, status, expiry, classification, family members, abstract.
• Medium confidence: identification of the three independent‑claim groupings (diagnostic method; kit use; composition for use) — these follow explicitly from the specification's "first/second/third aspect" language and the reference to "the method of claim 1."
• Low confidence / not verified: the verbatim text and exact numbering of the granted claims of US 11,402,389 B2.

If you need the verbatim granted claim set, the authoritative sources would be USPTO PatentCenter for application 16/483,784 or the granted‑patent PDF; I was unable to pull those directly here.

I'll search for litigation involving US patent 11402389 across patent litigation databases.

Let me search patent litigation databases more specifically.

Let me run a few more targeted searches to be thorough.

Litigation Search Results: US Patent No. 11,402,389

Bottom line

I found no litigation — filed, pending, or concluded — involving US Patent No. 11,402,389 (US11402389B2). Based on the searches I was able to run against patent‑litigation resources (Unified Patents portal references, Docket Alarm/PTAB materials, Justia federal docket documents, and CourtListener docket results), this patent does not appear as an asserted patent in any identifiable district court or Federal Circuit action.

What the patent is (context)

• Patent: US 11,402,389 B2 — "Biomarkers for diagnosing implant related risk of implant revision due to aseptic loosening"
• Application: US 16/483,784 (PCT national stage)
• Priority date: 2017‑02‑07; Filed: 2018‑02‑07; Granted: 2022‑08‑02
• Assignee of record (as listed): Lyfstone BV (originally Lyfstone AS → Orthogenics AS → Lyfstone AS → Lyfstone B.V.)
• Inventors: Stein Lian; Jarle Mikalsen; Eric Bendiksen; Anders Einung Hansen
• Subject matter: Calprotectin / S100A8 / S100A9 in synovial fluid; asserted claim 1 is a method of treating implant‑related risk of revision (administering anti‑inflammatory drug therapy for 4–50 mg/L, or revision surgery for ≥50 mg/L)

Case-by-case table

No case entries can be populated for any of the requested fields (plaintiff, defendant, jurisdiction, case number, filing date, outcome/status) because no suit asserting this patent was found.

Important disambiguation notes

Several search hits contained the string "389" or "11402389," but none involve this patent — I am explicitly not treating them as matches:

• The "389 patent" in litigation documents (e.g., Solos Technology v. Meta Platforms, D. Mass.; eMagin "'389" matters; IBM v. Zillow "'389" patent) refers to entirely different patents (e.g., U.S. 10,306,389 in the Solos/Meta case, which is a different patent number). These are NOT US 11,402,389.
• UK company number 11402389 ("BABY MINERAL LIMITED," Companies House) is a corporate registration number, not a patent.
• "11402389" in a Brazilian exam/result list (CESPE/UnB) is an unrelated personnel ID.

Confidence and caveats

• Confidence that no litigation exists as of the search date: moderately high, but not absolute. Litigation databases are not always fully indexed in general web search, and very recent filings (post‑index) could exist outside my reach.
• I was unable to complete all planned searches (further queries to Docket Navigator, RPX, PACER, and the Unified Patents litigation caselist were cut off due to a search‑step limit).

Recommended verification steps to confirm before relying on this: search PACER (all district courts, party name "Lyfstone" and patent number "11402389"), Docket Navigator, RPX Insight, Unified Patents Portal litigation caselist (https://portal.unifiedpatents.com/litigation/caselist), and CourtListener/RECAP using the exact patent number. Note also that Lyfstone markets a calprotectin PJI test, so any enforcement activity would likely be brought by Lyfstone B.V. as plaintiff — a useful search key.

If you can share the specific litigation resource you want me to re-query (e.g., a CourtListener or Unified Patents URL), I can re-run a focused search.

Proceedings overview

Zero AIA trial proceedings are on file for US 11,402,389 — no IPR, no PGR, no CBM, and no derivation proceeding — per the structured "PTAB proceedings on file" feed from the USPTO Open Data Portal (which returns an empty result set), and my independent web searches surfaced no petition, institution decision, final written decision, appeal, or Board docket naming Lyfstone, Orthogenics, or the '389 patent. There is therefore no petitioner-side win to lean on and no claim that has been canceled or construed by the Board; the defensive posture is "clean slate, no estoppel, but no free head start either" — the patent is fully intact and un-adjudicated at the PTAB, and any IPR you file will be the first.

Because there are no proceedings, the per-proceeding template is not populated. What follows is the strategic picture built from the patent's own record (Google Patents: https://patents.google.com/patent/US11402389/en).

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No proceedings to itemize

Verified by:

• USPTO Open Data Portal / PTAB structured feed — returns no AIA trials for patent number 11,402,389 (the canonical source for this task).
• PTAB E2E / Patent Trial and Appeal Board EndPoint — no case indexed against the '389 patent: https://ptacts.uspto.gov/ptacts/
• CourtListener / CAFC docket search — no Federal Circuit appeal involving the '389 patent or its owner Lyfstone B.V. surfaced: https://www.courtlistener.com/?q=Lyfstone
• Targeted web searches (Lyfstone + IPR, Orthogenics + PTAB, "11,402,389" + IPR/PGR) — returned only prosecution, EPO/BR family equivalents, product/CE-IVD literature, and unrelated Orthogen International GmbH matters (a different, Regenokine-related company — do not conflate it with Orthogenics AS, the '389 applicant).

If a petition has been filed very recently and not yet ingested by ODP, it would not appear here. Treat the "no activity" conclusion as accurate as of the ODP ingest date, with the standard caveat that filings within the last ingest cycle can lag.

Key dates that govern whether a challenge is even available

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Strategic summary

Claim status: everything is UNTESTED. No claim of the '389 patent has been canceled, confirmed, or construed by the PTAB, because no AIA trial has ever been instituted. The patent issued on 2022-08-02 covering a method of diagnosing implant-related risk of revision by detecting calprotectin, S100A8, and/or S100A9 in synovial fluid, with the specification tying the § 314 threshold analysis to concrete cut-offs (e.g., ≥4 mg/L = risk of revision; 4–50 mg/L = "pathology initiation"; >50 mg/L = "acute pathology") and an ELISA/lateral-flow readout. None of that claim scope has been narrowed or validated externally. There are no "surviving claims" to list because none were ever at risk, and correspondingly no FWD to quote — I will not manufacture one.

Estoppel landscape: a complete blank. Because no IPR or PGR was ever instituted, § 315(e)(2) estoppel attaches to no one. There is no petitioner, no privy, and no "grounds raised or reasonably could have raised" that a defendant inherits or is blocked by. For a defendant being asserted against today, the entire IPR toolbox is open: any patents or printed publications under § 102/§ 103, including art that might have been apparent to a hypothetical earlier challenger. Two practical limits remain: (1) the § 315(b) one-year bar — if you or a real party in interest/privy were served with a complaint alleging infringement more than one year ago, you are time-barred from filing an IPR on this patent; and (2) the PGR window has closed, so the only PTAB vehicle left is IPR (patents/printed publications, § 102/§ 103). Eligibility (§ 101) and disclosure (§ 112) challenges — which are the most natural attacks on a diagnostic-method claim of this type — are unavailable at the Board and must be litigated in court.

Pattern signals: none. There is no repeat petitioner (there is no petitioner at all), no patent-owner appeal history at the CAFC, and no defensive aggregator (Unified Patents, RPX, etc.) visible in the chain. The ownership history is a benign corporate-restructuring sequence — Lyfstone AS → Orthogenics AS (assignment 2019-08-06) → Lyfstone AS (name change 2020-06-26) → current assignee Lyfstone B.V. (2022-08-23) — not a litigation-driven transfer to an NPE. Lyfstone is an operating med-tech company selling a CE-IVD calprotectin point-of-care test, so assertion risk is likely tied to the PJI diagnostic product market rather than to a licensing campaign.

Family note (verify before relying): the EPO family listing for EP 3 580 571 B1 references later US grants in this family — reported as US 12,148,885 B2 (2024-11-19) and US 12,203,940 B2 (2025-01-21) (the EPO record renders the first as "US 1214885"), plus US 2019/0361035 A1. Those continuations have their own, later PGR windows and IPR exposure. I have not independently validated those grant numbers, so confirm them on Google Patents/ODP before citing; if they are live continuations, a challenger targeting the family should assess them separately — an IPR win against the '389 alone would not clear the continuation claims.

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Recommended next steps

• No PTAB activity exists — say so plainly in any validity opinion. The absence is itself a signal: the patent has been on file since 2022 and in the family since 2017 without attracting a single IPR. That most often means either (a) no one has yet had sufficient commercial incentive to challenge it, or (b) the diagnostic-method claims are narrow/commercialization-specific enough that competitors haven't felt exposed. It is not evidence that the claims are strong — it just means the record is silent.
• If you were served more than one year ago, check § 315(b) immediately. With no prior petitioner, there is no estoppel to navigate, but the one-year bar is a hard cutoff and is the single most common reason a first IPR never gets filed.
• Best-art hunt against the '389 priority date (2017-02-07), not the 2022 grant date. Because no earlier petition framed the art, you get to choose the primary references. Focus on pre-2017 synovial-fluid calprotectin publications (the specification itself cites Wouthuyzen-Bakker-type work on the 50 mg/L PJI threshold), which are exactly the kind of printed publications that both anticipate the "acute pathology" cut-off and arguably render the 4 mg/L / 4–50 mg/L brackets obvious.
• Route § 101/§ 112 attacks to district court. The PGR door closed 2023-05-02. Map any eligibility (Mayo/§ 101 diagnostic-method) or written-description theory to a district-court invalidity contention under § 282, and preserve it — it cannot be run at the PTAB.
• Watch for newly-ingested petitions. Since ODP lags, re-check the PTAB feed and E2E before finalizing a stay motion or a § 315(b) calculation: https://ptacts.uspto.gov/ptacts/ and https://patents.google.com/patent/US11402389/en (Legal Events tab).

Bottom line for a defendant: there is no PTAB proceeding to cite, no canceled claim to point at, and no estoppel to work around — the '389 patent is untested and fully alive. Your realistic PTAB option is a first-filed IPR on § 102/§ 103 art, subject only to the § 315(b) clock; your § 101/§ 112 theories must be fought in court.

I'll research the assignment chain for US 11,402,389 using the sources available to me.

Ownership & Assignment Record: US Patent No. 11,402,389 (US11402389B2)

Method note / data limitation: The primary source (USPTO Assignment Center, assignmentcenter.uspto.gov) was not directly reachable from my tool set, so I could not pull reel/frame numbers or the correspondent-of-record for the recorded assignments. Everything below is cross-checked against the Google Patents legal-events record in the authoritative full text of this patent (which mirrors the recorded post-issuance assignments) plus corroborating public records. Where I could not obtain a field, I say so rather than inventing it. Verify reel/frame and correspondent at: https://assignmentcenter.uspto.gov/ (search patent number 11402389).

⚠️ Contradiction flagged vs. the earlier Litigation section. That section describes "asserted claim 1" as a method of treating (administering anti-inflammatory drug therapy / revision surgery). The granted description here indicates the first aspect (claim 1) is a diagnostic method — "providing a biological sample from a subject with an implant; detecting a level of at least one polypeptide selected from the group consisting of calprotectin, S100A8 and S100A9." The treatment aspect is the third aspect ("a composition for use in the treatment of a subject that has been diagnosed … according to the method of claim 1"). The claim set is not reproduced verbatim in the provided text, so treat the "method of treating" characterization as unverified pending the actual granted claims.

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Inventors

Four named inventors, all residents of the Tromsø region of Norway at the relevant time (per the USPTO issue notice for the related continuation US 12,203,940):

• Employer basis: The recorded assignment of 2019-08-06 names the assignors as "BENDIKSEN, Eric; HANSEN, ANDERS EINUNG; LIAN, Stein; MIKALSEN, Jarle" conveying to ORTHOGENICS AS. This is the inventors-assign-rights-to-the-employer event and is the strongest direct evidence of their employer at filing. (Note the name-order discrepancy in the record: "HANSEN, ANDERS EINUNG" vs. patent-front "Anders Einung Hansen" — reported literally, not corrected.)
• Unusual-pattern check: No evidence of inventors departing the original assignee within 12 months of filing. All four reside in the Tromsø cluster where Orthogenics AS was founded (Jan 2012, Tromsø); the portfolio stayed intact through the 2020 name change and the 2022 intra-group transfer. Not determinable whether any inventor formally left, but there is no fire-sale signal.

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Original assignee

• Entity named on the issued patent (front page): Google Patents lists the Original Assignee as "Lyfstone AS" and the Current Assignee as "Lyfstone BV".
• The true originating entity was Orthogenics AS (Tromsø, Norway), founded January 2012. Per the recorded events, the inventors assigned rights to Orthogenics AS (2019-08-06); Orthogenics AS then changed its corporate name to Lyfstone AS (recorded 2020-06-26); Lyfstone AS then assigned to Lyfstone B.V. (2022-08-23). "Lyfstone AS" on the front page is therefore the renamed original assignee, not a separate first owner.
• Primary line of business: Norwegian med-tech / IVD diagnostics for orthopedics — "informative and functional biomarkers for the orthopaedic market," built on calprotectin measured in synovial fluid to risk-stratify periprosthetic joint infection (PJI) and aseptic loosening.
• Product embodying the claims: Yes. The group commercializes the Lyfstone® Calprotectin for Synovial Fluid point-of-care lateral-flow test (product codes LYFCLP001/LYFCLP005; CE-IVD marked; ~15–17 min result read via the Lyfstone Reader smartphone app), developed in collaboration with Calpro AS (Norway). The claimed diagnostic concept — calprotectin in synovial fluid at the 4/14/50 mg/L thresholds — is the company's core product.
• Current status: Operating. The group is now headquartered at Papehof 49, 1391 BE Abcoude, Netherlands (Lyfstone B.V.); the Norwegian operating arm was Lyfstone AS (Tromsø). Related continuation US 12,203,940 ("Biomarkers for diagnosing implant related risk of implant revision due to aseptic loosening," Norwegian inventors) issued Jan 21 to Lyfstone B.V., confirming an ongoing, product-driven portfolio rather than a liquidation remnant.

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Assignment timeline

Chronological recorded events (dates are the recorded/event dates surfaced in the legal-events record; execution dates and reel/frame were not retrievable):

• Recorded 2019-08-06 — Reel NNNNNN/NNNN: not retrieved

  • Conveyance: Assignment (inventors → company)
  • Assignor: Bendiksen, Eric; Hansen, Anders Einung; Lian, Stein; Mikalsen, Jarle (the four inventors)
  • Assignee: Orthogenics AS
  • Correspondent: not retrieved — could not obtain; flag for manual pull.
  • Context: Founding assignment — inventors perfect the company's title to the application (coincides with ~30-month US national-stage entry; US 2019/0361035 A1 published 2019-11-28).

• Recorded 2020-06-26 — Reel NNNNNN/NNNN: not retrieved

  • Conveyance: Change of Name
  • Assignor: Orthogenics AS
  • Assignee: Lyfstone AS
  • Correspondent: not retrieved
  • Context: Internal reorg / name change only — same legal entity rebranded; no change in economic ownership.

• Recorded 2022-08-23 — Reel NNNNNN/NNNN: not retrieved

  • Conveyance: Assignment
  • Assignor: Lyfstone AS
  • Assignee: Lyfstone B.V.
  • Correspondent: not retrieved — this is the link where the correspondent is most diagnostically useful (post-grant intra-group transfer to the Dutch parent); flag for manual pull.
  • Context: Intra-group transfer — Norwegian operating subsidiary → Netherlands group holding/operating entity, recorded ~3 weeks after grant (2022-08-02). Same corporate family; not a transfer-to-asserter.

(No other recorded assignments appear in the legal-events record. There is no recorded security agreement, license, release, or corrective assignment.)

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Timeline diagram

timeline
    title Ownership of US 11402389
    2017 : Priority application filed
    2018 : PCT application filed by Orthogenics AS
    2019 : Inventors assign rights to Orthogenics
         : US national stage published 20190361035
    2020 : Orthogenics AS renamed Lyfstone AS
    2022 : Patent granted as US 11402389 B2
         : Assigned to Lyfstone B.V.
    2025 : Continuation US 12203940 issues to Lyfstone

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NPE / troll-pattern signals

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Verdict

Operating-company assertion — with the explicit caveat that the "assertion" prong is currently unmet (no suit found). Best read as operating-company ownership, non-asserting.

Justification (2–3 sentences): The chain is a short, clean corporate-reorganization sequence — inventors → Orthogenics AS (recorded 2019-08-06) → name change to Lyfstone AS (recorded 2020-06-26) → intra-group assignment to Lyfstone B.V. (recorded 2022-08-23) — terminating at a med-tech operating company that ships a product embodying the claimed calprotectin/synovial-fluid diagnostic (the CE-IVD Lyfstone® Calprotectin for Synovial Fluid test) and that continues to prosecute related family members (e.g., continuation US 12,203,940, issued Jan 21 to Lyfstone B.V.). Zero of the eight NPE signals are affirmatively present; the only unresolved item is signal #3 (correspondent-of-record), which is a data-retrieval gap, not evidence of a pattern. I could not retrieve reel/frame numbers or correspondents — verify the three entries above at the USPTO Assignment Center (https://assignmentcenter.uspto.gov/, patent 11402389) and confirm the correspondent on the 2022-08-23 Lyfstone AS → Lyfstone B.V. recording before treating this verdict as final.

I'll search for the cited prior art references for US 11,402,389.

Let me try to access the patent's citation records directly.

I found a citation list, but it's attached to a related family member. Let me pull the actual "References Cited" for US 11,402,389 itself.

Prior Art Analysis — US 11,402,389 B2

Verification status (read first)

I want to be explicit about what I could and could not obtain, because it materially limits the confidence of this section.

• Patent identity confirmed. US 11,402,389 B2 ("Biomarkers for diagnosing implant related risk of implant revision due to aseptic loosening"), App. 16/483,784, Lyfstone B.V. — matches the number exactly. No similar-number substitution was performed.
• I could not retrieve the verbatim "References Cited" front page of US 11,402,389 itself. My searches did not return the grant's own citation block, and I hit the tool step limit before completing a direct PATENTSCOPE/PatentCenter pull. This is a real gap, not a claim I verified.
• What I did retrieve is the citation list for a sibling in the same family — US 12,146,885 (same specification, filed as a continuation) — whose front page lists its own "Referenced Cited" and which itself cites US 11,402,389 as a U.S. patent document. Because it shares the identical specification and examiner art unit, this list is a strong proxy for the art cited against US 11,402,389, but it is a proxy, not the 11,402,389 front page. I flag every place where this matters.
• US 11,402,389 also has extra top-level filings in the family I had not previously surfaced: US 12,203,940 B2 (Jan 21, 2025) in addition to US 12,146,885 (Nov 19, 2024). These are different patent numbers and must not be attributed to 11,402,389.

⚠️ Contradiction to flag (per instruction)

The previously generated sections contradict each other on what claim 1 of US 11,402,389 recites:

• The Patent summary section states claim 1 is the diagnostic method.
• The Litigation summary section states "asserted claim 1 is a method of treating implant‑related risk of revision (administering anti‑inflammatory drug therapy for 4–50 mg/L, or revision surgery for ≥50 mg/L)."

These cannot both be right for the same patent. On the intrinsic record I was given, the diagnostic reading is better supported: the specification's third aspect defines the composition claims as "for use in the treatment of a subject that has been diagnosed … according to the method of claim 1," which only makes sense if claim 1 is the diagnostic method. The "method of treating" language matches US 12,146,885, not 11,402,389. I treat the Litigation summary's characterization as an apparent conflation and do not rely on it. Verbatim granted claim text remains unverified.

Because of that, the §102 mapping below uses the element-level claim structure (summarized from the specification and the pre-grant publication US 2019/0361035 A1), not asserted claim numbers.

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Element set used for the §102 analysis

Independent diagnostic claim (element labels for reference):

Anticipation under §102 requires one single reference disclosing all elements as arranged. §103 requires the differences be obvious over the art.

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Prior art references

The following is the citation set surfaced from the family record. Full citations and dates are as listed on the sibling patent's face; I have not independently verified each date against the primary document.

A. U.S. Patent Documents

B. Foreign Patent Documents

C. Non-Patent Literature (most probative)

Note: The ISR for PCT/EP2018/053044 (listed as N8) would list the examiner's relevance categories (X/Y/A) and the specific claims to which each reference relates. That is the authoritative answer to "which reference anticipates which claim," and it is precisely the document I could not pull.

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§102 anticipation analysis

Honest conclusion up front: on the record I can access, none of these references is a clean §102 anticipation of the independent claim. Each is missing at least one claim element, and the missing element is the one that appears to carry the novelty (the combination of synovial fluid + implant subject + the numeric ≥4 mg/L / staged thresholds). They are best characterized as §103 obviousness art, with N4 (Dapunt 2014, prosthetic interfaces / aseptic loosening) the closest.

Why the independent claim resists §102

The patent's own specification shows the advance was framed as solving a specific unmet need — detecting loosening "at an early stage … even in asymptomatic patients" — via synovial fluid at the implant site with defined cut-offs (4 mg/L; 4–50 vs. >50 mg/L). No single reference in the retrieved set discloses all of: (i) synovial-fluid sampling at an implant, (ii) calprotectin/S100A8/S100A9 as the analyte, (iii) the numeric threshold, and (iv) the secreted-not-intracellular limitation. That is consistent with the family having granted (US 11,402,389 issued 2022; EP 3580571 B1 granted 2023-06-07; RU 2757771 C2; JP 7108638 B2) over this art.

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What I could not verify (please treat as open)

1. The actual "References Cited" list of US 11,402,389 B2. Everything in Section "Prior art references" is drawn from the sibling US 12,146,885 and may differ in details from the 11,402,389 face.
2. The ISR for PCT/EP2018/053044 (N8) with its X/Y/A categorizations — the decisive document for a defensible anticipation mapping.
3. Subject matter of P1 (US 5,776,348), P3, P5, F1–F4. I did not read these documents and will not guess at their disclosures.
4. Verbatim granted claims, including the claim-1 identity flagged above.
5. Whether N7 (Nordal 2017) pre-dates the 2017‑02‑07 priority — this changes its §102/§103 status.

Recommended verification steps

• USPTO PatentCenter, App. 16/483,784 → "References Cited" and the "Patent Family" tab, for the verbatim front-page citations of 11,402,389.
• PATENTSCOPE / WIPO, PCT/EP2018/053044 → the International Search Report and Written Opinion (N8).
• USPTO Patent Public Search / Global Dossier for the EP 18708053.6 examination file, whose office actions (referenced in the sibling's citation list) would show exactly which references the examiner applied against which claims.
• PACER/CourtListener for "Lyfstone" are not needed here (that was the litigation task), but the same assignee key is useful if infringement history becomes relevant.

Bottom line: The number is confirmed as US 11,402,389 B2. The retrieved art — anchored by the Dapunt prosthetic-interface work (N4/N2/N3) and the older L1/calprotectin joint-fluid work (N1) — is close but not anticipatory on the elements I can see; it reads as §103 material. The claims' apparent preservation turns on the synovial-fluid-at-implant + numeric-threshold combination, but I cannot confirm that against the grant's own citation block or the ISR without the direct USPTO/WIPO records named above.

I'll run targeted prior-art searches relevant to the §103 analysis, focusing on calprotectin/S100A8/S100A9 in synovial fluid and orthopedic implant loosening/infection diagnosis.

Let me search for pre-2017 prior art specifically, since the priority date is 2017-02-07.

Let me pin down the pre-2017 state of the art for synovial-fluid calprotectin and check the priority-date-relevant publication timing.

Analysis of Obviousness under 35 U.S.C. § 103 — US 11402389 B2

Scope note and a flagged contradiction. I am analyzing US 11402389 B2 (Biomarkers for diagnosing implant related risk of implant revision due to aseptic loosening; app. 16/483,784; priority 2017‑02‑07; filed 2018‑02‑07; granted 2022‑08‑02; assignee Lyfstone BV).

The previously generated sections contain an internal contradiction I want to flag explicitly before proceeding:

• The Patent summary section states claim 1 is the diagnostic method (detect calprotectin/S100A8/S100A9 in synovial fluid; <4 vs ≥4 mg/L), and expressly says the treatment‑recast recitation belongs to a different patent, US 12,146,885.
• The Litigation summary section instead states that "asserted claim 1 is a method of treating implant‑related risk of revision (administering anti‑inflammatory drug therapy for 4–50 mg/L, or revision surgery for ≥50 mg/L)."

These cannot both be right, and the second appears to have imported the US 12,146,885 subject matter into 11402389. I resolve this in favor of the Patent summary, and there is independent corroboration: the Chinese family member CN110446929A lists as its 主权项 (claim 1) "一种诊断植入物相关的修复风险的方法" — "a method of diagnosing implant‑related risk of revision," comprising providing a biological sample from a patient with an implant and detecting calprotectin/S100A8/S100A9, wherein the sample is synovial fluid. That is the diagnostic method, not a treatment method. See http://transport.motcats.ac.cn/Search/get/[743983](/patent/743983)?db=cats_zhuanli_jt.

I still do not have the verbatim granted US claim set (low confidence per the earlier section), so the chart below uses claim elements as they appear in the specification's "first/second/third aspect" language and in the family claim text. Wording and numbering should be verified against PatentCenter.

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1. Legal framework and level of ordinary skill

The obviousness inquiry follows Graham v. John Deere (scope/content of prior art; differences; PHOSITA level; secondary considerations), applied flexibly under KSR Int'l v. Teleflex (motivation may come from "any need or problem known in the field," common sense, and market/design incentives; predictable arts permit combination by "simple substitution of one known element for another"). For ranges and thresholds, In re Aller (a range is obvious if the prior art teaches values "close to" the claimed range or the range is the result of routine optimization) and In re Woodruff ("a recognized practical boundary") apply.

PHOSITA: An M.D. orthopedic surgeon, or a Ph.D./M.S. clinical chemist or immunologist, with ~3–5 years' experience in (a) periprosthetic joint diagnostics/revision arthroplasty and/or (b) immunoassay biomarker development (sandwich ELISA, lateral‑flow immunoassay). This is a predictable, well‑characterized art (immuno‑detection of a known protein in a known body fluid), which lowers the bar for combining references.

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2. The prior art and its status (literal identifiers preserved)

Caveat I must state plainly: If PA‑1's only public availability was the May 2017 print issue, it is not prior art against a 2017‑02‑07 effective filing date, and the whole obviousness case must then rest on PA‑3 through PA‑9. That combination is still viable (see Ground 1), but PA‑1 is the reference that most cleanly maps onto the claim. A challenger should first establish the online‑first date of PA‑1 (BJJ publishes accepted manuscripts online), and/or whether the 2017‑02‑07 priority application actually supports the full S100A8/S100A9 genus and the 4‑ and 50‑mg/L thresholds. If the priority document is narrower than granted claim 1 — a common outcome — the effective date for the broader genus could fall to the 2018‑02‑07 PCT filing, making PA‑1 and PA‑2 both squarely prior art.

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3. Ground 1 — The diagnostic method (calprotectin in synovial fluid; ≥4 mg/L)

Proposed combination: PA‑1 (primary) in view of PA‑5/PA‑6/PA‑7 (motivation) and PA‑4 (detection means); alternatively PA‑3 + PA‑8 + PA‑4 + PA‑6/PA‑7 where PA‑1 is unavailable.

Claim‑element mapping (against the family claim text and specification aspects):

Motivation to combine (KSR‑sufficient):

1. Same field, same problem, same sample. PA‑1 is not a remote reference: it is directed to the identical problem ("diagnosing or excluding a prosthetic joint infection … [in] revision surgery") using the identical sample type (synovial fluid from an implant site). Combining it with the admitted background art (PA‑5–PA‑7) requires no field‑crossing.
2. Articulated need in the art. The specification itself admits the problem (Background): "there is still a need for further biomarkers, and in particular biomarkers that are easily detectable at an early stage of implant loosening even in asymptomatic patients," and "a need for cost effective methods." PA‑1 supplies exactly the identified need — it calls synovial calprotectin "cheap," "easy to use," and quantifiable by LFA in ~20 minutes.
3. A finite, predictable set of candidates. PA‑5 (IL‑6/IL‑8), PA‑6 (PICP/OPG/TNF‑α/NTX/RANKL/IL‑1β) and PA‑7 (MCP‑1) had already established that synovial/periprosthetic inflammatory proteins track implant loosening. A PHOSITA looking to extend that panel would predictably look to the other neutrophil‑derived alarmins — calprotectin being the most abundant cytosolic neutrophil protein (~60% of soluble cytosol, as the spec acknowledges) and already validated in synovial fluid for RA/JIA (PA‑3).
4. Reasonable expectation of success. The mechanism was known: calprotectin is released by activated neutrophils/macrophages at sites of joint inflammation (PA‑3, PA‑8), and both septic and aseptic loosening involve neutrophil/macrophage activation at the bone‑implant interface (PA‑8). Measuring a known analyte with a known assay (PA‑4) in a known fluid yields an expected correlation — "obvious to try" under KSR.

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4. Ground 2 — The S100A8 and S100A9 species claims

The specification treats S100A8, S100A9 and calprotectin as interchangeable alternatives (it states calprotectin "is a complex of" S100A8 and S100A9 and lists all three in the alternative in every claim as recited in the family). Where a reference teaches a genus or a complex, and the members are known in the art, separate claims to the members are prima facie obvious.

• PA‑8 discloses S100A9 (MRP14) gene expression at osteolytic sites in aseptic loosening and in implant‑associated infection tissue.
• PA‑3 / PA‑9 disclose S100A8 and S100A9 (MRP8/MRP14) as secreted markers measurable in synovial fluid and serum.
• PA‑4 supplies the ELISA platform.

Motivation: Because calprotectin is the S100A8/S100A9 heterodimer, an artisan who wants to detect "calprotectin" necessarily detects (or can trivially choose to detect) its constituent monomers; there is no change in principle of operation. KSR ("substitution of one known element for another to obtain predictable results").

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5. Ground 3 — The numeric thresholds and the "pathology initiation" window (4–50 mg/L)

This is the weakest link in the applicant's position, because it rests on numeric ranges without disclosed criticality.

• 50 mg/L: squarely disclosed by PA‑1 (which used 50 mg/L as its cutoff against infection). Under In re Woodruff, the boundary is a "recognized practical boundary," so a claim to >50 mg/L as "acute pathology" is prima facie obvious.
• 4 mg/L: PA‑1's own control distribution (median 11, IQR 3–29 mg/L) brackets 4 mg/L; the spec's own Table 1 shows "no risk of revision" samples at 0.74–3.23 mg/L and "risk" samples ≥4.28 mg/L, i.e., a clean split that is the expected result of optimizing a cutoff in a bimodal distribution. Under In re Aller, selecting a threshold from within a disclosed range, absent evidence of a criticality not otherwise apparent, is routine optimization. Notably, the spec does not state any reason why 4 mg/L (rather than 3 or 5) produces a result that would be unexpected; it simply fixes the value by reference to the CALPROLAB™ kit.
• "Pathology initiation" (4–50 mg/L) and "acute pathology" (>50 mg/L): PA‑1 already teaches the dichotomy it calls "chronic PJI" (low‑grade) vs "acute PJI," with an intermediate zone. The relabeling as "pathology initiation"/"acute pathology" is a naming choice, not a technical difference.

Counter‑argument the applicant could raise (see §7): that the 1–50 mg/L / 4–50 mg/L window unexpectedly captures asymptomatic patients destined for revision, i.e., that the window's endpoints are critical. That requires evidence in the specification of unexpected results at the boundary. The spec's own data actually undercut this: the data set contains a false negative (sample F1, aseptic loosening at 0.95 mg/L) and a false positive (sample F2, "no risk of revision" at 105 mg/L), which is exactly the kind of routine scatter one expects from a threshold correlation, not a hallmark of a critical range.

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6. Ground 4 — The kit claims (second aspect)

Claim elements: a solid support coated with monoclonal antibodies specific for calprotectin/S100A8/S100A9; a washing solution; an alkaline‑phosphatase‑labelled polyclonal conjugate; p‑nitrophenyl phosphate substrate.

• PA‑4 (WO 2013/132347) discloses a calprotectin ELISA kit with these general components; the CALPROLAB™ kit described in Example 1 of the patent is itself a commercial embodiment of that prior art, not something the applicant invented.
• PA‑1 discloses a lateral‑flow immunoassay kit for synovial calprotectin.
• PA‑9 discloses an S100A8/S100A9 ELISA using monoclonal/polyclonal sandwich format.

Motivation/reasoning: A monoclonal‑capture / polyclonal‑detection sandwich ELISA with AP conjugate and pNPP substrate was a textbook, conventional configuration in 2017 (the spec itself cites The Immunoassay Handbook, ch. 10). Choosing it for synovial calprotectin is "a combination of familiar elements according to known methods [that] yields predictable results." The "use of a kit for diagnosing" claim format adds only the intended use, which follows from Ground 1.

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7. Ground 5 — The composition‑for‑use claims (third aspect)

Elements: a composition comprising an anti‑osteolytic and/or anti‑phlogistic/anti‑inflammatory agent, for use in treating a subject diagnosed by the method of claim 1, including asymptomatic subjects and subjects not having acute pathology.

• If claim 1's diagnostic method is obvious (Grounds 1–3), then the "for use in treating a subject diagnosed by [that] method" limitation carries little independent weight — the novelty resides in the diagnostic step, not the agents.
• The recited agents are all conventional: bisphosphonates for periprosthetic osteolysis, NSAIDs/cortisone for joint inflammation, and antibiotics (vancomycin, gentamicin, etc.) for the infection arm. The Background itself states that pathology initiation "may favorable be treated by e.g. using anti‑inflammatory drugs."
• Motivation: The specification frames the goal as "increasing the chance of avoiding revision surgery" via drug treatment of early‑stage loosening. Treating an inflammation‑driven osteolytic condition with an anti‑inflammatory/anti‑osteolytic agent is an obvious application once the diagnosis is available.

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8. Where the obviousness case is weakest — and what would defeat it

An honest assessment requires identifying the applicant's best defenses:

1. PA‑1's prior‑art status. If PA‑1 was not publicly available before 2017‑02‑07, Ground 1 must be rebuilt on PA‑3 + PA‑8 + PA‑4 + PA‑5/6/7. That combination is still strong for the genus (calprotectin/S100A8/S100A9 in synovial fluid) but is materially weaker on the specific 4‑ and 50‑mg/L thresholds, and cannot lean on PA‑1's express 50 mg/L value.
2. The negative limitation ("secreted and not intracellular content of intact cells"). This may be argued as a point of novelty. It fails as an obviousness defense if the prior art inherently or expressly measures supernatant (PA‑1 centrifuged and used supernatant); but if the applicant can show the prior art taught no caution against cell lysis, it becomes an argument about why a PHOSITA would have arrived at the limitation. This is the applicant's most technically defensible point.
3. Criticality of the 4 mg/L boundary. If the applicant has evidence (or can add it via a continuing application) that 4 mg/L — and not, say, 10 or 20 mg/L — uniquely identifies the treatable, asymptomatic "pathology initiation" population with a clinically meaningful effect on revision avoidance, that could rebut In re Aller. The current specification does not make that showing.
4. Objective indicia. I found no evidence of unexpected results, long‑felt need satisfied by others' failure, industry praise, licensing, or copying that the applicant could invoke. The earlier sections found no litigation, so there is likewise no adjudicated record on secondary considerations. On the current record, the objective‑indicia factor is neutral‑to‑negative for patentability.
5. § 101 interplay (not § 103, but relevant to strategy). A claim whose "diagnosis" is "solely based on the detected level" of a naturally occurring protein is exposed to a Mayo/Alice challenge (natural correlation + conventional detection). That does not make the claims obvious, but it may explain why the family split into the separate treatment patent US 12,146,885 (per the earlier section) — a claim‑drafting workaround, not evidence of non‑obviousness.

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9. Bottom line

• Most probable §103 rejection: claim 1 (and dependent threshold/classification claims) over Wouthuyzen‑Bakker 2017 (PA‑1) as the primary reference, in view of the admitted background art (PA‑5/PA‑6/PA‑7) for motivation and WO 2013/132347 (PA‑4) for the detection means — the combination being motivated by (i) the art's express, unsatisfied need for a cheap, early, synovial‑fluid biomarker distinguishing septic from aseptic implant failure, (ii) a finite and predictable candidate set, and (iii) a reasonable expectation of success given calprotectin's established role as a neutrophil alarmin measurable in synovial fluid.
• If PA‑1 is disqualified on date, the fallback combination (PA‑3 + PA‑8 + PA‑4 + PA‑6/PA‑7) still renders the genus‑level claims obvious, but the numeric thresholds (4 and 50 mg/L) become the applicant's best hope of survival.
• Species (S100A8/S100A9), kit, and composition‑for‑use claims are individually weaker than claim 1 and fall to KSR‑style substitution-of‑known-elements and predictable‑result reasoning.
• What to verify before relying on this analysis: (a) the verbatim granted claims of US 11402389 B2 via PatentCenter for app. 16/483,784 — I could not retrieve them; (b) the online‑first publication date of PA‑1; (c) the disclosure content of the 2017‑02‑07 priority application (does it support the full genus and both thresholds?); (d) whether any secondary‑considerations evidence exists (none found).

Confidence: Medium‑high on the identity and content of the prior‑art references and on the legal framework; low‑to‑medium on the exact metes and bounds of the granted claims (verbatim text not obtained); and I explicitly flag PA‑1's prior‑art date as unresolved rather than assuming it in the applicant's or challenger's favor.