US 11046742

I'll search for this patent and any related 2026 CAFC docket activity.

Let me try additional targeted searches.

Let me check for any 2026 litigation or Federal Circuit activity involving this patent or its owner.

US Patent 11,046,742 B2 — Analyst Summary

Sourcing note / confidence

I was not able to retrieve live results from the USPTO Patent Public Search system or a Federal Circuit 2026 docket database in this session — searches for the patent number returned no USPTO or CAFC docket records, and my queries for Yuhan/Federal Circuit 2026 activity returned nothing before I hit the retrieval limit. The summary below is grounded in the authoritative full text of US11046742B2 (Google Patents, fetched 2026‑09‑11) and corroborating third‑party mirrors (Justia, FreePatentsOnline, PubChem, Patents‑Review). I cannot confirm from authoritative sources whether this patent is the subject of any 2026 CAFC appeal or district‑court litigation — I have no such information.

Bibliographic data

Abstract (verbatim)

"Provided are a fusion protein having a CCL3 variant with improved in vivo persistency, protein stability and pharmacological activity and a use thereof, more particularly, a fusion protein comprising a CCL3 variant and an immunoglobulin Fc region and a use thereof as a therapeutic agent for lymphopenia, cancer or infection, in which an N-terminal amino acid of a wild-type CCL3α or CCL3β is deleted and an amino acid at a specific position is substituted with a different amino acid at the same position of the wild-type CCL3α or CCL3β in the CCL3 variant."

Plain-language overview of the independent claims

The patent has 8 claims. Only claim 1 and claim 6 are independent; claims 2–5 incorporate claim 1 by reference, and claims 7–8 depend from claim 6.

Claim 1 — The fusion protein (composition of matter)

A fusion protein made of two parts joined by a linker:

• Part 1 — the CCL3β variant: specifically the polypeptide of SEQ ID NO: 4. (Per the specification, SEQ ID NO: 4 is human wild-type CCL3β of SEQ ID NO: 3 with two N‑terminal residues removed, i.e., Δ1‑2 "AP" deletion, and the aspartic acid at position 27 replaced with alanine — the "D27A" substitution.)
• Part 2 — the immunoglobulin Fc region: specifically the hybrid Fc of SEQ ID NO: 14 (a hybrid IgG4/IgD Fc, described as corresponding to the hybrid Fc form of Korean Patent Registration No. 0897938).
• The linker: specifically SEQ ID NO: 5, i.e., the 12‑residue peptide RNTGRGGEEKKK (formula (RNT)ₙGRGG(EEKKK)ₘ with n = m = 1).

In plain terms: the claim is narrowly drawn to one specific construct — the "CCL3B‑H05" molecule — rather than to the broader genus of variants discussed in the specification (which also covers CCL3α variant SEQ ID NO: 2, other linkers SEQ ID NOs: 5–13, and linker‑less fusion via SEQ ID NO: 17).

Claim 2 — Nucleic acid

A nucleic acid (DNA/RNA) encoding the claim‑1 fusion protein. (Formally worded as depending on claim 1, but is an independent‑scope product claim to the encoding polynucleotide.)

Claim 3 — Vector

A vector (e.g., plasmid/viral expression vector) comprising the claim‑2 nucleic acid.

Claim 4 — Cell

A cell transformed with the claim‑3 vector.

Claim 5 — Method of preparing the fusion protein

A method with two steps: (a) culturing a cell transformed with a vector comprising a nucleic acid encoding the fusion protein; and (b) collecting (recovering/purifying) the fusion protein from the cultured cell.

Claim 6 — Method of treatment (independent)

A method for treating cancer comprising administering a pharmaceutical composition comprising the claim‑1 fusion protein.

Claim 7 — Combination with radiation

The claim‑6 method wherein the composition is administered in combination with radiation treatment.

Claim 8 — Adjunct to radiation

The claim‑6 method wherein the composition is administered to assist radiation treatment.

Supporting data reported in the specification (context for the claims)

• CCR1 receptor reactivity (Tango™ CCR1‑bla assay): CCL3 ≈ 0.63 nM; CCL3A‑H05 ≈ 16.0 nM; CCL3B‑H05 ≈ 11.6 nM.
• Chemotaxis (THP‑1): CCL3B‑H05 (linker H05, SEQ ID NO: 5) outperformed CCL3B‑H40 (no linker) — supporting the linker limitation in claim 1.
• Stability: CCL3B‑H05 showed low high-molecular-weight aggregate content (≈1.2% at day 0; ≈1.0% after 5 weeks at 37 °C) at ~9.5 mg/mL.
• Pharmacokinetics (mice, IV): half‑life ≈20.4 h (3 mg/kg) and ≈45.6 h (10 mg/kg), vs. ≤~1.7 h for native CCL3 in humans; linear PK over 3–10 mg/kg.
• Efficacy (BNL 1ME A.7R.1 mouse liver cancer + 6.5 Gy irradiation): ~72% tumor growth inhibition for CCL3B‑H05 10 mg/kg vs. ~25% for CCL3A‑H05.

Key uncertainty flags

1. No CAFC/2026 docket data retrieved. I found no evidence of a 2026 Federal Circuit appeal or litigation involving US 11,046,742. This is not a confirmation that none exists — only that my searches returned nothing.
2. No live USPTO database hit. The bibliographic and claim data above come from the patent's own text; the "Active" legal status is a listed assumption in the source (Google Patents expressly disclaims it as a legal conclusion). PTAB/IPR activity, terminal disclaimers, or maintenance‑fee lapse were not verified.
3. Inventor/assignee attributions from third‑party pages (e.g., "Su‑Jin Ahn — 30 Patents at Samsung") should be treated as unreliable; the authoritative assignee is Yuhan Corporation.
4. The specification describes a broader family of variants and linkers than the claims capture; the granted claims (post‑prosecution) are limited to the CCL3B‑H05 construct, which is a notable narrowing relative to the written description.

I'll search for litigation involving US patent 11046742 across multiple sources.

Let me search more specific litigation sources.

Let me check the Unified Patents litigation portal and other dedicated litigation sources directly.

Litigation Search Results for US Patent 11046742

Bottom line: I found no evidence of any litigation involving US Patent 11046742.

What I searched

I queried multiple sources aimed at patent litigation, including:

• General web searches for the patent number combined with "litigation," "lawsuit," and "infringement"
• The Unified Patents litigation portal (portal.unifiedpatents.com)
• CAFC / Federal Circuit and PACER-oriented queries
• Assignee-based searches (Yuhan Corporation) and technology-based searches (CCL3-Fc fusion protein)

Findings

No matching litigation records were returned. The results that surfaced were either irrelevant (e.g., hits on a different patent number, US20120046742, which belongs to an unrelated family) or were non-litigation patent-family records showing the same patent across jurisdictions (KR, EP, JP, CN, AU, BR, CA, MX, NZ, RU, WO, ZA), all commonly owned by or derived from Yuhan Corporation.

Important caveats

1. Negative results are not proof of absence. The freely accessible sources I could reach did not include paywalled litigation databases (e.g., Darts-ip/Clarivate, Lex Machina, Bloomberg Law). A definitive clearance-style check for litigation would require those tools plus direct PACER and CAFC docket searches, which I could not fully execute within this session.
2. Patent identity confirmed literally. US 11046742 B2 ("Fusion protein comprising CCL3 variant and use thereof"), application US16/097,572, filed 2017-04-19, granted 2021-06-29, priority 2016-04-29, assignee Yuhan Corporation. This is the exact patent you asked about — I did not auto-correct or substitute any number.
3. The litigation-focused search for other similarly numbered patents (e.g., US20120046742) returned unrelated matters and should not be attributed to this patent.

Suggested next steps to confirm

• Run a direct docket search in PACER and CourtListener/RECAP for "11046742."
• Query Darts-ip, Lex Machina, or Unified Patents Portal with a subscription login for the exact number.
• Check USPTO Patent Center / Assignment records and the USPTO Patent Trial and Appeal Board (PTAB) for any IPR/PGR or appeal proceedings, which can indicate a dispute even absent district-court litigation.

If you'd like, I can attempt a narrower search (e.g., just PTAB proceedings for this patent) in a follow-up.

I'll verify the canonical "no PTAB activity" signal against public sources before writing.

Let me run additional targeted searches to make sure nothing is hiding in less-indexed corners.

Proceedings overview

Total PTAB proceedings on file for US 11,046,742: zero (0 active / 0 claims invalidated / 0 claims sustained / 0 settled / 0 institution denials) — the USPTO Open Data Portal returns no AIA trial proceedings for this patent, and my public-source checks (PTAB docket indexes, CAFC/CourtListener, and targeted searches naming the patent, its applicant publication US20190153055A1, and the assignee Yuhan Corporation) surfaced none — which means the patent has never been tested in an AIA trial, and a defendant cannot point to any cancelled claim, any institution decision, or any Federal Circuit disposition as a shortcut; the entire claim set must be attacked from scratch, or a settlement/commercial strategy pursued instead.

Because the count is zero, the per-proceeding template below is intentionally empty of invented content. I am not populating it with placeholder proceeding numbers, petitioner names, or "typical" outcomes — none exist here.

No proceedings to report

• Type: N/A — no Inter Partes Review, Post-Grant Review, or Covered Business Method review has been instituted, filed, or terminated against US 11,046,742.
• Filed: N/A
• Status: The ODP block states, verbatim: "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 filed (or none has been docketed/indexed) against this patent.
• Judge panel: None — no panel has ever been assigned.
• Petition grounds: None.
• Institution decision: None. No institution or denial date exists to report.
• Final Written Decision: None.
• Settlement / termination: None.
• Appeal: None. No CAFC docket exists for this patent, so there is no appeal number or disposition to cite.
• Defensive value: You are in the rare position of facing a clean, un-threatened claim set — no prior petitioner has narrowed it, no estoppel has been created, and no PTAB record exists that you can mine for admissions about the art. Conversely, you also inherit none of the benefit a prior petitioner's win would have handed you.

Search caveat (practical, not legal): the string "11046742" collides with an unrelated application number — US 11/046,742 (David Mormile / Mark Vinton, "Spring supported dual element face seal," published as US20050167927A1). Keyword docket sweeps on the bare number will return seal-technology hits and produce false positives. Search instead on "11,046,742" with the comma, on US20190153055A1, or on assignee "Yuhan."

Strategic summary

Claim status: all 8 claims UNTESTED; nothing cancelled, nothing sustained. No claim of US 11,046,742 has ever been construed by the PTAB or cancelled through an AIA trial. For reference, the granted set is narrow and sequence-specific: claim 1 recites a fusion protein comprising a CCL3β variant of SEQ ID NO: 4 linked through a linker of SEQ ID NO: 5 to an immunoglobulin Fc region of SEQ ID NO: 14; claims 2–5 are the nucleic acid / vector / cell / preparation-method family; claims 6–8 are method-of-treatment claims for cancer, with claims 7–8 reciting combination with, or assistance to, radiation treatment. There is no suggestion in the record that any of these have been held invalid, and I have found no evidence they have been adjudicated anywhere. Note also that the EPO counterpart EP3448880A4 is recorded as withdrawn and the WO is recorded as ceased — that is prosecution/Opposition-division history, not an AIA trial, and it does not bear on US claim validity. Do not let anyone conflate the two.

Estoppel landscape: a blank slate. Because no petitioner has ever filed, § 315(e)(2) estoppel is entirely unavailable as a sword against you — no petitioner or privy has any ground "raised or reasonably could have raised" that would be barred. Equally, you bear no inherited estoppel. Practically, every § 102 and § 103 ground you can develop against the SEQ ID NO: 4 / SEQ ID NO: 5 / SEQ ID NO: 14 combination remains fully available for an IPR or for district-court invalidity. The filing-eligibility notes that matter: the patent is post-AIA (filed 2017-04-19, priority 2016-04-29), so it was PGR-eligible only during the 9-month window after grant (2021-06-29), which closed on or about 2022-03-29 — PGR is no longer available; IPR remains available indefinitely, subject to the § 315(b) one-year bar running from service of a complaint alleging infringement.

Pattern signals: none of the usual ones. No serial petitioner, no defensive aggregator (no Unified Patents, RPX, or similar entity appears anywhere in the paper trail), and no PTAB appeal activity by the patent owner — there is simply no proceeding to appeal. The one genuine signal is the absence of IPRs, and it should be read cautiously: this is a 2021-granted, still-Active patent (anticipated expiration 2037-04-19) covering a narrowly claimed sequence combination, and the prior art (chemokine-Ig fusion work from the 1997–2011 era, e.g., the Genetics Institute chimeric chemokine-domain filings and the 2011 chemokine-immunoglobulin fusion work cited on the face of the patent) suggests the claims were deliberately drawn narrow to survive it. A narrow, sequence-locked claim set plus no commercial assertion campaign is the ordinary explanation for zero IPRs — not necessarily evidence of unusual strength.

Recommended next steps

If you are a defendant facing assertion right now:

1. Do not cite a PTAB outcome — there isn't one. Any argument of the form "claims 1–5 were cancelled" or "the Board already invalidated this" would be a fabrication and sanction exposure. The only accurate statement is: no AIA trial has ever been filed or instituted against US 11,046,742. Verify this yourself against USPTO PTAB E2E and the PTAB Decisions search before filing anything, since ODP ingest lags.
2. Watch the § 315(b) clock from day one. Service of a complaint alleging infringement starts a hard one-year window to petition for IPR. Because § 315(e)(2) estoppel is not yet in play for anyone, you can file without inherited constraints — but you forfeit the option entirely if the year lapses.
3. Forget PGR. The post-grant window on this 2021 grant is long closed; do not budget for a § 112 or written-description attack in a PGR. § 112 challenges belong in district court or in a § 282 defense, not in an IPR (which reaches only § 102/§ 103 on patents and printed publications).
4. Attack the claim-1 sequence lockup, not "CCL3-Fc" generally. Claim 1 requires all three of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 14 together. That is a narrow target — build your invalidity and non-infringement theories at the junction (the Δ1-2/D27A CCL3β variant, the RNTGRGGEEKKK linker, and the IgG4/IgD hybrid Fc), and mine the patent's own cited art for § 103 motivation to combine a chemokine variant with an Ig Fc.
5. Note the radiation-treatment hooks in claims 7–8. Method claims reciting administration "in combination with" and "to assist" radiation treatment can be vulnerable on inducement/divided-infringement and on written-description grounds if the specification's single mouse allograft example (BNL 1ME A.7R.1, 6.5 Gy, ~72% tumor growth inhibition at CCL3B-H05 10 mg/kg) is the only support.
6. If a settlement path is preferred, the complete absence of prior PTAB activity means there is no public record of the patent owner's claim-construction positions, expert admissions, or prior-art concessions — you would be negotiating without that intelligence, which cuts toward early targeted discovery or a focused validity study rather than going in blind.

If you simply need to know whether this patent is a paper tiger: I cannot tell you that with high confidence from the public record, and I will not manufacture a PTAB narrative to fill the gap. What I can state with confidence is that US 11,046,742 has no AIA trial history of any kind, is currently Active, carries a 2037-04-19 anticipated expiration, and is asserted in no PTAB proceeding on file as of the most recent ODP ingest.

I'll research the assignment record and ownership context for US patent 11046742. Let me run several targeted searches.

Assignment & Ownership Analysis — US 11046742 B2

Patent identity (literal, not auto-corrected): US 11046742 B2, "Fusion protein comprising CCL3 variant and use thereof"; application US 16/097,572; §371 national phase of PCT/KR2017/004199; filed 2017-04-19; priority KR 10-2016-0053018 (2016-04-29); granted 2021-06-29; anticipated expiration 2037-04-19; status Active. Source of record data: Google Patents legal-events feed for US11046742B2 (fetched 2026-09-11).

Data-availability note: The Assignment Center / assignment.uspto.gov record could not be queried directly in this session (tools returned no live results for reel/frame lookups). The analysis below rests on the legal-events record embedded in the authoritative patent text and on corroborating public sources. Reel/frame numbers are not present in the fetched record and are deliberately left unstated rather than invented. A direct Assignment Center search by patent number would be required to confirm reel/frame and the correspondent of record.

Inventors

Fourteen named inventors (all listed as assignors on the single recorded assignment to Yuhan Corporation, which strongly indicates common employment by the original assignee at filing):

Employer at filing: Determined by the assignment itself — the 2018-11-27 record is an assignment of assignors' interest from all fourteen inventors to YUHAN CORPORATION, i.e., the standard employee→employer confirmation of an obligation-to-assign. No independent evidence of any inventor's employment elsewhere at filing exists in the record; all fourteen are treated here as Yuhan personnel.

Pattern notes:

• No evidence of inventors departing the original assignee, and no inventor-side (individual) ownership survives anywhere in the chain — this is a company-held portfolio, not an inventor-held one.
• ⚠️ Name-collision caution: a public aggregator (patentleaderboard.com) attributes "Su-Jin Ahn" to Samsung with 30 patents and separately lists US11046742 in that inventor page. This is almost certainly an aggregation/homonym artifact — the patent's own record names Su Jin Ahn as a Yuhan assignor, and the invention is Yuhan's CCL3 program. Do not read a Samsung connection into this patent.
• The inventor count (14) is large but typical for a biologic-engineering filing where a team of molecular biologists contributed.

Original assignee

Yuhan Corporation (Korean: 주식회사 유한양행), assignee on the face of the issued patent and current assignee of record.

• Business: Korean pharmaceutical manufacturer, KRX-listed (ticker 000100), founded 1926, HQ 74 Noryangjin-ro, Dongjak-gu, Seoul. Segments: pharmaceuticals (Rx/OTC), overseas/raw materials, life & health (household, animal health). Ships marketed products — e.g., Leclaza (lazertinib) for NSCLC, plus generics/OTC lines (Anchupramin, PicoM-C, Yuhan Raks, etc.). This is an active operating company, ~1,600–2,150 employees, publicly traded and filing audited annual reports.
• Product embodying the claims: The CCL3-Fc variants in this patent (CCL3A-H05, CCL3B-H05) are shown in the specification as preclinical/experimental fusion proteins. I found no evidence of a currently marketed product practicing SEQ ID NO: 4 linked through SEQ ID NO: 5 to the SEQ ID NO: 14 hybrid Fc. Yuhan runs immuno-oncology assets through its subsidiary ImmuneOncia Therapeutics Inc.; however — per the constraint against speculation — no assignment to ImmuneOncia is recorded for this patent in any source I could reach.
• Current status: Operating, solvent, not in bankruptcy. No Chapter 7/11 analog, no delisting, no asset fire-sale.

Assignment timeline

Only one recorded assignment appears in the record, and it is the initial inventor→company confirmation:

• 2018-11-27 (recorded) / executed date not shown in the fetched record — Reel not shown in fetched data
  • Conveyance: Assignment of Assignors' Interest (ASSIGNMENT OF ASSIGNORS INTEREST — SEE DOCUMENT FOR DETAILS)
  • Assignor: AHN, SU JIN; CHOI, BYUNG HYUN; CHUNG, SOO YONG; KANG, HO WOONG; KIM, JONG GYUN; KIM, KI HONG; KIM, SEUL GI; LEE, JUN KYUNG; LEE, JUNE HYUNG; LEE, NA RAE; NAM, Su Youn; OH, SE WOONG; PARK, JU YOUNG; SHIN, SEUNG YUB (all named inventors)
  • Assignee: YUHAN CORPORATION
  • Correspondent: Not exposed in the fetched record (Assignment Center must be queried directly to obtain the recording attorney/firm). No recurrence can be assessed without it.
  • Context: Internal/initial acquisition — employees confirm assignment of the CCL3-Fc invention to their employer. Not a sale, securitization, or transfer to a third party.

Post-issuance transfers: none recorded. No assignment, security agreement, merger, change-of-name, or release appears after grant (2021-06-29). The "Current Assignee" remains Yuhan Corporation.

Because only the original assignment exists, the analysis of shell entities, cascading transfers, and pre-litigation transfers terminates here — there is simply no downstream chain to evaluate. That absence is itself the principal finding: Yuhan retained the patent.

Timeline diagram

timeline
    title Ownership of US 11046742
    2016 : Priority filing by Yuhan
    2017 : PCT and US national phase filed
    2018 : Inventors assign to Yuhan Corporation
    2021 : Patent granted to Yuhan Corporation
    2026 : Still held by Yuhan Corporation

NPE / troll-pattern signals

Cross-reference: the earlier litigation summary for this patent also found no litigation (district court, PTAB, or CAFC) involving US 11046742 — consistent with a retained, non-asserted operating-company patent.

Verdict

Insufficient data (only the original assignment).

Justification: The entire recorded chain consists of a single link — the 2018-11-27 instrument by which the fourteen named inventors assigned their interest to YUHAN CORPORATION — with no subsequent assignment, security interest, merger, or license recorded after grant on 2021-06-29. The assignee is an active, solvent, KRX-listed pharmaceutical manufacturer (Leclaza/lazertinib and a large marketed portfolio) that still owns the patent; there is no shell entity, no known asserter, no cascading transfer, and no defensive-aggregator endpoint. With only the original assignment present and the recording correspondent/reel-frame not retrievable in this session, none of the NPE signals can be affirmatively established, so the record supports neither an NPE finding nor an operating-company assertion finding (no suit exists). Re-run this analysis against the USPTO Assignment Center record to capture the reel/frame and correspondent of record and confirm the single-link chain.

Verify at: USPTO Assignment Center — https://assignmentcenter.uspto.gov/ (search US 11046742 / application 16/097,572); mirrored at https://assignment.uspto.gov/patent/index.html.

I'll search for the patent and its cited references to build an accurate prior-art analysis.

Let me search the remaining key references, particularly those most likely to be anticipatory.

Let me verify a few remaining references.

Prior-Art Analysis — US 11046742 B2

0. Patent under analysis (identity confirmed literally)

Claim 1 (the only independent composition claim) is extremely narrow. It requires all three specific sequences:

• SEQ ID NO: 4 — human CCL3β variant (deletion of N-terminal Ala-Pro Δ1-2 + D27A substitution),
• SEQ ID NO: 5 — linker RNTGRGGEEKKK,
• SEQ ID NO: 14 — hybrid Fc (IgG4/IgD hyFc).

Dependent/method claims 2–8 (nucleic acid, vector, cell, preparation method, cancer-treatment method ± radiation) all inherit the same three-sequence limitation.

Analytical bottom line: Because claim 1 is sequence-defined (SEQ ID NOs 4, 5, 14), no cited reference anticipates any claim under 35 U.S.C. § 102 — none discloses that exact combination. The references below are, however, the material prior art against the genus recited in the specification (a CCL3/CCL3-variant–immunoglobulin Fc fusion), and they are the references an examiner or a challenger would use under § 103 (obviousness), or under § 102 only if complemented by the specific sequences. I flag per-reference whether the disclosure reaches the "all-elements" § 102 threshold.

Caveat / contradiction flag: The "previously generated" litigation section asserts no litigation exists for this patent. That is consistent with what I see (no litigation references in the patent record or search results). No contradiction with this analysis. My § 102 conclusions below rest on the patent's own face citations (Google Patents / USPTO text provided) plus targeted verification searches; a definitive § 102 call requires a full-text sequence-by-sequence comparison of each reference, which I could not fully retrieve for every one of the 18 references.

1. Most relevant references (Tier 1 — reach the core Fc-fusion concept)

1.1 Genetics Institute — "Chimeric polypeptides containing chemokine domains"

• WO 1998038212 A2 — priority 1997-02-28; published 1998-09-03.
• US 6,730,296 B1 (Herrmann & Swanberg) — granted 2004-05-04; and US 6,100,387; continuation US 7,396,911 B2.
• Description: Recombinant polynucleotides encoding a chemokine polypeptide covalently attached to a heterologous polypeptide (expressly including an immunoglobulin/Fc moiety), expressly listing the CC family that includes MIP-1α (CCL3). Discloses the rationale (short 8–10 kDa chemokine half-life → Fc fusion to extend persistence), chemotactic-recruitment utility, and MIP-1α as a CCR1/CCR4/CCR5 ligand.
• § 102 reach: Discloses the generic element "CCL3/chemokine + immunoglobulin Fc covalent fusion." It does not disclose the Δ1-2 deletion, the D27A substitution, SEQ ID NO: 4, the SEQ ID NO: 5 linker, or the SEQ ID NO: 14 hyFc. → Anticipates nothing literally as claimed; it is the strongest § 103 reference against the Fc-fusion genus of claim 1 and against claims 6–8 (cancer/chemotaxis utility). My search of the reference confirms GPL-licensed text showing MIP-1α-bound-receptor disclosure and Ig-fusion embodiment.

1.2 Genexine — "Immunoglobulin fusion proteins" (the hyFc platform)

• US 2008/0300188 A1 — priority 2007-05-30 (US prov. 60/940,753); published 2008-12-04.
• Granted as US 7,867,491 B2 (2011-01-11); related CN 103641919 A; US 2011/0091416 A1.
• Description: Discloses a hybrid human Fc comprising IgG4 and IgD ("hyFc") joined via an optional linker to a biologically active molecule, designed to increase serum half-life with reduced ADCC/CDC. This is the direct technological ancestor of SEQ ID NO: 14 — the Yuhan specification states the hybrid Fc "may be equal to, for example, a hybrid Fc form disclosed in Korean Patent Registration No. 0897938," i.e., the same hyFc family.
• § 102 reach: Discloses the Fc element (hyFc, IgG4/IgD) and the "biologically active molecule–linker–Fc" architecture, but not the CCL3β variant or the specific linker/Chemokine. → Does not anticipate claim 1 as a whole; highly relevant § 103 reference for the SEQ ID NO: 14 element (and it is the reference that effectively pre-dates/underlies the Fc recited in claim 1).

1.3 Morehouse School of Medicine — "Chemokine–immunoglobulin fusion polypeptides"

• JP 2014-518632 A — priority 2011-06-01; published 2014-08-07 (family: US 8,541,564 B2).
• Description: Expressly claims isolated nucleic acids encoding chemokine–IgG-Fc fusion polypeptides with N-terminally truncated chemokines and chemokine mutants (e.g., CCL2(5-76), CCL7(5-76), CCL8, CCL13, CCL25, CXCL11, CXCL13 fused to IgG1/IgG2/IgG3/IgG4 Fc). Teaches N-terminal truncation + point mutation of a CC chemokine as a design strategy to retain activity in an Fc fusion.
• § 102 reach: Discloses the generic strategy (CC-chemokine N-terminal truncation/mutation + Fc fusion) — the same strategy Yuhan used. The enumerated chemokines I retrieved do not include CCL3β or the specific SEQ ID NO: 4, and no SEQ ID NO: 5 linker or SEQ ID NO: 14 is disclosed. → No literal anticipation; strong § 103 reference against the variant design concept.

1.4 Biotherapix Molecular Medicines — "Mono- and bifunctional molecules with ability to bind to GPCRs"

• WO 2007/113285 A2 — priority 2006-03-31; published 2007-10-11 (A3 pub. 2008-05-08).
• Description: Chemokine fusion proteins comprising at least one chemokine or chemokine variant and a constant-region portion of an immunoglobulin that binds the corresponding chemokine receptor and inhibits cell migration (antagonist design; CCL2/CCL5 emphasized).
• § 102 reach: Discloses "chemokine variant + immunoglobulin constant region" fusion, and specifically teaches mutating chemokines. Not CCL3β, SEQ ID NO: 4, or SEQ ID NO: 5 / SEQ ID NO: 14. → No literal anticipation; § 103 reference for the variant–Fc genus.

2. CCL3-specific / sequence-adjacent references (Tier 2 — bear on the chemokine and its utility)

2.1 British Biotech — "Stem cell inhibiting proteins"

• US 5,856,301 A — priority 1991-12-23; granted 1999-01-05 (sibling JP H07502404 A, pub. 1995-03-16).
• Description: MIP-1α (CCL3) stem-cell inhibitor proteins; supports the lymphopenia/myeloprotection utility recited in the Yuhan specification.
• § 102 reach: Discloses CCL3 (MIP-1α) per se and its utility. Does not disclose the variant, linker or Fc. → Relevant to § 102 only for the unclaimed wild-type background; supports § 103 for claim 6's therapeutic use.

2.2 Schering Corporation — "MCP1 fusion"

• JP 2009-504158 A — priority 2005-08-12; published 2009-02-05.
• Description: Fusion protein of a CC chemokine, MCP-1 (CCL2), with a heterologous partner (Fc-type) for half-life extension.
• § 102 reach: CCL2, not CCL3β; no SEQ ID NO: 4/5/14. → No anticipation; § 103 reference showing CC-chemokine-Fc fusion was known.

2.3 Vaccibody AS — "Homodimeric protein constructs"

• US 2013/0171140 A1 — priority 2010-06-25; published 2013-07-04.
• Description: Homodimeric protein constructs (vaccine targeting units) in which chemokines (incl. CCL3/MIP-1α family) are dimerized, e.g., via an Ig-derived dimerization domain, for targeting immune cells.
• § 102 reach: Dimer/multimer chemokine targeting constructs, but not the SEQ ID NO: 4 variant or the SEQ ID NO: 5/14 combination. → No anticipation; § 103 reference for the dimer/multimer aspect referenced in the specification.

2.4 University of Vermont — "CCL18 and CCL3 methods and compositions for detecting and treating cancer"

• US 8,445,442 B2 — priority 2007-04-26; granted 2013-05-21.
• Description: CCL3 (and CCL18) compositions/methods in cancer.
• § 102 reach: CCL3's cancer utility (claim 6 context) only; no variant/Fc sequences. → Relevant to § 103 for claim 6.

2.5 Applied Research Systems / ARS Holding — chemokine-mutant references

• JP 2005-522192 A — priority 2001-07-19; published 2005-07-28 (multimeric proteins).
• JP 2005-525089 A — priority 2001-12-17; published 2005-08-25 ("Chemokine mutants acting as chemokine antagonists").
• JP 2006-514699 A — priority 2002-12-23; published 2006-05-11 ("Use of CC chemokine mutants for liver disease").
• Description: Engineered CC-chemokine mutants (antagonists) and their therapeutic use — establishes that mutating a CC chemokine (incl. MIP-1α/CCL3) to alter receptor activity was known before 2016.
• § 102 reach: Disclose chemokine mutants, but not the D27A/Δ1-2 CCL3β variant of SEQ ID NO: 4 or any Fc fusion. → No anticipation; § 103 references against the "introduce a mutation at a specific position" concept, and against claim 6/7 (liver disease / therapeutic use).

3. Remaining cited references (Tier 3 — peripheral; no § 102 bearing on claim 1)

4. Consolidated § 102 conclusion

Key takeaway: On the face-cited prior art, no reference anticipates any claim of US 11046742. The examiner allowed claim 1 specifically because the three-sequence combination (SEQ ID NOs 4, 5, 14) is not disclosed or suggested by the art. The references that come closest — Genetics Institute (WO 1998/038212 / US 6,730,296 / US 6,100,387), Genexine's hyFc (US 2008/0300188 / US 7,867,491), Morehouse (JP 2014-518632 / US 8,541,564), and Biotherapix (WO 2007/113285) — would be the backbone of an obviousness (§ 103) challenge to the genus, but each individually fails the § 102 "all-elements-in-a-single-reference" test against claim 1.

5. Methodological notes, limitations, and suggested verification

1. Source of the citation set: the reference list is the patent's own face citations (Google Patents / USPTO text, fetched 2026-09-11). I verified several via live search (Genetics Institute, Genexine, Morehouse, Biotherapix). I was unable to complete full-text retrieval for JP 2005-522192, JP 2005-525089, JP 2009-504158 and US 5,856,301 within this session (search step limit reached), so their descriptions are drawn from titles/bibliographic data and family metadata — treat those characterization details as provisional.
2. § 102 vs. § 103: As requested, I assessed anticipation only. None of the cited references meets the single-reference, all-elements standard for claim 1 (or its dependents). Any real invalidity argument would be an obviousness argument combining, e.g., Genetics Institute (chemokine-Ig fusion) + ARS chemokine mutants (point mutation) + Genexine hyFc.
3. Sequence verification needed: A rigorous § 102 analysis requires an alignment of SEQ ID NO: 4 (Yuhan CCL3β variant) against the chemokine sequences disclosed in the Genetics Institute and Morehouse references, and of SEQ ID NO: 14 against the Genexine hyFc sequences. That step could not be completed here and should be run against the ST.26/sequence listings.
4. Recommended primary sources for final confirmation:
   • USPTO Patent Center / Global Dossier for application 16/097,572 (IDS and examiner-cited art).
   • Google Patents / Espacenet for full text of WO 1998/038212, US 6,730,296, US 2008/0300188, US 8,541,564, WO 2007/113285.
   • The examiner's Form PTO-892 citation list (the 18–21 references tabulated above) to confirm which references were actually applied (as opposed to merely listed).

I'll ground this analysis by verifying the key prior-art references listed in the patent's citation section before building the § 103 combinations.

Let me pin down the ECI301 mutation identity, N-terminal truncation prior art, and the ARS Holding chemokine-mutant disclosure.

Obviousness Analysis — US 11,046,742 B2 (Yuhan Corp.)

"Fusion protein comprising CCL3 variant and use thereof" — 35 U.S.C. § 103

Analyst note on scope and sources. This analysis is built on (a) the patent text and citation lists supplied (authoritative), and (b) targeted verification searches run against the references cited on the face of the patent. It is an examiner-style/prima-facie obviousness assessment, not a validity opinion. Where I could not verify a reference's specific disclosure, I say so explicitly rather than assume it. Nothing in the earlier Litigation summary contradicts anything below; litigation status is irrelevant to the § 103 question except that the granted patent carries a statutory presumption of validity (§ 282) requiring clear-and-convincing evidence to invalidate in court (preponderance in an IPR).

1. Governing framework

• Effective filing date: 2016-04-29 (KR priority 10-2016-0053018); PCT filed 2017-04-19; granted 2021-06-29. AIA § 102(a)(1)/(a)(2) applies; all references below published well before 2016-04-29.
• Legal standard: Graham v. John Deere, 383 U.S. 1 (1966) (scope/content of art; differences; PHOSITA level; secondary considerations); KSR Int'l v. Teleflex, 550 U.S. 398 (2007) (predictable combinations, "obvious to try" where a finite number of identified, predictable solutions exists); MPEP 2141–2144.
• PHOSITA: a protein engineer/immunologist with an advanced degree and several years' experience in chemokine biology and Fc-fusion biologics — including linker selection and N-terminal/C-terminal fusion orientation (R. Gentz-type skill).
• The claim is a product claim defined by three specified sequences. Obviousness does not require the art to recite the sequences; it requires that the art suggest the claimed structure with a reasonable expectation of success.

2. Claim 1 — limitation breakdown and where each element is taught

Observation bearing on patentability. Claim 1 covers only the CCL3β variant (SEQ ID NO:4). The specification also describes and exemplifies the CCL3α variant (SEQ ID NO:2 = Δ1 + D27A on LD78α) — which maps almost exactly onto the published ECI301/eMIP molecule — yet that species is not claimed. The narrowing to the β backbone is consistent with the α species being squarely in the art, which in turn means the claimed subject matter differs from the known α variant only by (i) the α→β backbone and (ii) one additional N-terminal residue (Δ1 → Δ1-2). Both differences are minor and well within routine practice.

3. Combinations that would render the claims obvious

Combination 1 (strongest) — ECI301 art + Genexine hyFc + Biotherapix/Morehouse

References: WO2012023631A1 (or the underlying ECI301 disclosures) + US20080300188A1 (hyFc) + WO2007113285A2 / JP2014518632A (chemokine-Fc + linker).

• Coverage: ECI301 supplies the result-effective mutation set (N-terminal deletion + D27A, chosen for reduced aggregation). Genexine supplies the Fc and expressly provides for a linker between Fc and payload. Biotherapix/Morehouse supply the chemokine-Fc architecture with CCL3 named and linkers taught.
• Motivation: The patent's own background concedes CCL3's 2 problems — half-life ≈ 1.7 h and precipitation at ≥0.1 mg/mL — and the art recognized Fc fusion as the standard long-acting solution (Genexine; US6730296 noting chemokines' "short biological half-lives"). The ECI301 work establishes the identical rationale (aggregation reduction) for the identical mutation. Combining a known aggregation-suppressing CCL3 variant with a known half-life-extending Fc carrier via a known linker is the epitome of a predictable, KSR "combination of familiar elements according to known methods."
• Result: All four limitations of claim 1 are met or suggested.

Combination 2 — British Biotech / ARS "chemokine mutants" + Genetics Institute chimeric chemokines + hyFc

• British Biotech's stem-cell-inhibitor work (US5856301; JPH07502404A) and ARS Holding's chemokine-mutant patents (JP2005525089A; JP2006514699A) teach engineered MIP-1α/CC M-chemokines with N-terminal modification and point mutations that tune activity/stability.
• Genetics Institute WO98/38212 / US6730296B1 teaches MIP-1α covalently fused to heterologous polypeptides (incl. Ig) expressly to overcome short half-life.
• Genexine supplies the specific hyFc of SEQ ID NO:14 (with the patent's own admission that this Fc is known).
• Motivation: same half-life/aggregation problems; the resulting chimera is a predictable assembly.

Combination 3 — Morehouse (CCL3-Ig fusion genus + truncation) + ECI301

• Morehouse (JP2014518632A / US8541564) claims a genus of chemokine–Ig fusions expressly including CCL3, and its exemplary constructs use N-terminally truncated chemokines (e.g., "CCL2(5-76)-IgG1Fc," "CCL8(5-76)-…," "CXCL11(4-73)-…"). I could not verify a worked CCL3 example in that family, so this is a genus-plus-truncation-motif teaching, not an anticipation of SEQ ID NO:4.
• ECI301 supplies the specific CCL3 mutation. Combined, a POSHITA would arrive at an N-terminally truncated, D27A CCL3 fused to an Ig Fc. Under KSR, selection of a species from a disclosed genus is obvious where the art provides a reason to select it (here: CCL3's known potency/aggregation profile and the β-isoform's known greater potency — see § 5).

Combination 4 — Vaccibody / Trubion / Schering chemokine-fusion platform art + ECI301 + hyFc

• Vaccibody US20130171140A1 ("homodimeric protein constructs") and Schering JP2009504158A ("MCP1 fusion") establish chemokine–Ig and dimeric chemokine-fusion scaffolds; Trubion JP2007528194A establishes binding-construct scaffolds. These reinforce that placing a chemokine payload on an Ig scaffold with a linker was routine.
• Again, combined with ECI301 + hyFc, claim 1 falls.

4. Motivation to combine (why a POSHITA would do it)

1. A recognized, unmet need: short half-life and concentration-dependent precipitation of CCL3 were documented in the art (the patent's own background; European Journal of Cancer 34:1023-1029 (1998); US6730296 noting rapid inactivation/short half-lives of chemokines).
2. A known solution: Fc fusion (and specifically the mutation-free IgG4/IgD hyFc designed for long action without ADCC/CDC) was a commercially validated half-life-extension platform (Genexine).
3. A known mutation strategy: N-terminal deletion and D→A substitution at the conserved aspartate of MIP-1α/CCL3 to suppress polymerization was known (ECI301/eMIP; BB-10010/nagrestipen) — with the same stated purpose ("inhibition of precipitation") recited in this patent's Table 1.
4. A finite, identified solution set: the patent's own Table 1 lists exactly the small menu (Δ1 or Δ1-2; D27A), confirming the design space was small and predictable — the KSR "finite number of identified, predictable solutions" scenario.
5. Linker selection is routine: the art taught that linkers relieve steric hindrance (Biotherapix) and Genexine expressly provided a linker between Fc and payload.

Reasonable expectation of success: all components are naturally-occurring human sequences; the standard recombinant-expression/purification workflow (Protein A + hydroxyapatite, exactly as the patent performs) was conventional. Nothing in the art taught away.

5. Claims 2–8

• Claims 2–5 (nucleic acid, vector, cell, preparation method): follow claim 1. Once a protein is obvious, a DNA encoding it, a vector, a host cell, and a culture/purify method are routine. No independent inventive weight.
• Claims 6–8 (method of treating cancer; with/assisting radiation): directly taught by the ECI301 literature cited in the patent's own background. Shiraishi et al., Clin Cancer Res 14:1159-1166 (2008) discloses intravenous ECI301 combined with local irradiation producing an abscopal antitumor effect; the 2014 Oncoimmunology review and Iida et al., Cancer Res 70:6347 (2010) (RFA) confirm the radiation-adjuvant concept. So even if claims 6–8 are treated independently, the "administered in combination with / to assist radiation treatment" limitations are squarely disclosed.

6. Likely non-obviousness counterarguments and their weakness

7. Contradictions, gaps, and items I could not confirm (read carefully)

1. Numbering discrepancy for the "D→A" residue. Published sources describe the engineered CCL3/MIP-1α variant as D27A (eMIP) but the BB-10010/nagrestipen literature is reported as D26A. This is almost certainly an off-by-one numbering convention (mature protein vs. precursor/with-initiator), not a different residue — but for claim-charting purposes the two must be reconciled against SEQ ID NO:3/SEQ ID NO:1. Do not treat D26A and D27A as automatically identical without sequence-level verification.
2. Explicit pre-2016 disclosure of the exact eMIP mutation. I verified the mutation (Δ1 + D27A) from a 2018 paper (Clinical and Translational Radiation Oncology 10:7-12) and a 2014 review that describes eMIP only as a "single amino-acid substituted CCL3." Both the 2018 paper and the earlier review post-date or are borderline to the 2016 priority date. The pre-priority document that must be checked for the explicit D27A recitation is WO2012023631A1 (ECI Inc.) — which is cited on the patent's face — together with the underlying ECI/Kanegasaki patent family and the British Biotech BB-10010 publications. Flagging explicitly: I did not confirm the literal "D27A" language in a document published before 2016-04-29.
3. Naturally occurring truncated LD78β. I could not verify whether an N-terminally AP-truncated LD78β (CCL3L1) occurs naturally. If it does, it would raise an independent § 102 concern for the variant per se — though claim 1 (a fusion) would still require the Fc/linker elements.
4. Morehouse family. CCL3 is recited in the chemokine genus, but I did not find a worked CCL3–Fc example; the specific constructs I saw use CCL2, CCL7, CCL8, CCL13, CCL25, CXCL11, CXCL12, CXCL13. Treat Morehouse as a § 103 teaching, not an anticipation reference.
5. Linker SEQ ID NO:5 provenance. The patent uses an internal code ("H05") for RNTGRGGEEKKK and lists SEQ ID NOs:5–13 as a Formula-1 series. I did not confirm that this exact linker is disclosed in Genexine's hyFc filings (it may instead be a Yuhan-designed linker). If the linker is not in the art, That is the strongest remaining non-obviousness hook, but it is a routine optimization point: the patent's own background concedes linker choice is a known, activity-controlling variable, and Genexine/Biotherapix teach that linkers belong in Fc fusions.

8. Bottom line

• Claim 1 is prima facie obvious under § 103 over ECI301/eMIP art (WO2012023631A1 + Shiraishi 2008) in view of Genexine's hyFc (US20080300188A1) and a chemokine-Fc/linker teaching (Biotherapix WO2007113285A2 or Morehouse JP2014518632A). Each limitation is taught or suggested; the motivation (half-life + anti-aggregation) is established; the solution set is finite and predictable; and there is no teaching away.
• Claims 2–5 are obvious as routine implementations; claims 6–8 are obvious additionally in view of the ECI301-plus-radiation abscopal art.
• The most defensible applicant position is (i) unexpected superiority of the β backbone and (ii) non-obviousness of the specific SEQ ID NO:5 linker — but objective evidence for (i) is undercut by the known higher potency of LD78β, and (ii) reduces to routine optimization. The most important evidentiary gap to close before asserting invalidity is confirming an explicit, pre-2016-04-29 disclosure of the Δ1 + D27A mutation (check WO2012023631A1 and the BB-10010 literature), and resolving the D26/D27 numbering.

Standards note: This is a prima-facie assessment under MPEP 2143. US 11,046,742 enjoys a § 282 presumption of validity; invalidation requires clear and convincing evidence, and any combination must be supported by an articulated, evidence-based motivation (In re Kahn; KSR).