Invalidity dossier
US 5556757
Peptides representing epitopic sites for bacterial and viral meningitis causing agents and their CNS carrier and uses thereof
Current assignee: Insight Biotech Inc
Added 9/27/2026, 2:50:07 PM
Active provider: DeepSeek · deepseek-flash
Patent summary
Title, assignee, inventors, filing/issue dates, abstract, and a plain-language overview of the claims.
I'll search for this patent in the requested databases.
Let me gather the full claim set and check the CAFC docket specifically.
Let me pull the actual claim set from the patent record.
US Patent 5,556,757 — Summary
Important scope note on the searches. I was able to confirm the patent through Google Patents and Justia, but I could not directly query USPTO PatentCenter or the CAFC docket system, and my web searches surfaced no CAFC 2026 appeal, docket entry, IPR, or litigation referencing 5,556,757. Treat the "no CAFC activity found" conclusion as a search limitation, not an authoritative negative — absence of a hit is not proof that no such proceeding exists.
Two near-miss identifiers surfaced and should not be confused with this patent: JP5556757B2 (a Japanese vehicle air‑conditioner patent) and a Brazilian filing/registration number 5556757. Neither is US 5,556,757.
Bibliographic data (from the patent record)
| Field | Value |
|---|---|
| Patent number | US 5,556,757 A |
| Application no. | US 08/482,847 |
| Title | "Peptides representing epitopic sites for bacterial and viral meningitis causing agents and their CNS carrier and uses thereof" |
| Inventors | Diane V. Alstyne; Lawrence R. Sharma |
| Assignee (original & current) | Insight Biotech Inc |
| Filing date | 1995-06-07 |
| Priority date | 1993-09-28 (parent App. Ser. No. 08/127,499, filed Sep. 28, 1993; this patent is a divisional of that allowed application) |
| Issue/publication date | 1996-09-17 |
| Status | Expired – Fee Related (anticipated expiration 2013-09-28) |
| Representative classifications | C07K14/005; C07K14/195; C07K14/22; C07K14/3156; C07K16/*; A61K38/00; A61K39/00 |
Abstract (as recorded)
"Peptides comprising a Meningitis Related Homologous Antigenic Sequence (MRHAS) are provided. The MRHAS is found in meningitis-causing organisms and chemokines involved in cell chemotaxis. The peptides are useful as antigens and vaccines for detection, diagnosis and treatment of meningitis."
Plain-language overview
The core scientific story. The inventors made a monoclonal antibody (designated RV1-Mab, from hybridoma cell line RV-1, deposited as ATCC HB 11362 on May 26, 1993) raised against rubella virus (RV). They found that this single antibody cross-reacted with proteins from the major bacterial meningitis pathogens — Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae, Listeria monocytogenes — as well as HIV-1. The shared, cross-reactive short peptide sequences were collectively named MRHAS ("Meningitis Related Homologous Antigenic Sequence"). The inventors further noted homology of these sequences to the C-terminal region of the monocyte-attracting chemokines hMCP-1 and hMCP-3, and proposed that meningitis agents exploit monocyte chemotaxis (via chemokine-like recognition) to gain CNS access. The specification's examples use immunoblots (FIGS. 12–13) to show RV1-Mab binding to the bacterial and HIV antigens.
The claimed family is built around seven-amino-acid epitope blocks, exemplified by QPQPPRM (SEQ ID NO:3, RV core region) and PPQPPCA (SEQ ID NO:7, RV E2 region), and by the hMCP-1 sequence QTQTPKT (SEQ ID NO:37).
Independent claim 1 (the peptide claim — verbatim structure, condensed). A peptide of the formula a—X—b, where:
aandbare each linked toXby a simple peptide bond; andXis an MRHAS contained in the amino acid sequence of a protein or peptide found in a bacterium or virus that is an etiologic agent of meningitis, "said protein or peptide is a chemokine involved in cell chemotaxis," andXis at least 7 sequential amino acids (plus conservative substitutions/modifications) selected from a recited group (i)–(xv), each defined by positional correspondence to a reference sequence:
| Item | Source protein (SEQ ID NO) | Residues |
|---|---|---|
| (i) | RV M33 Structural Polyprotein (SEQ ID NO:1) | 102–108 |
| (ii) | RV M33 Structural Polyprotein (SEQ ID NO:1) | 89–95 |
| (iii) | RV M33 Structural Polyprotein (SEQ ID NO:1) | 313–319 |
| (iv) | RV Therien Structural Polyprotein (SEQ ID NO:8) | 103–109 |
| (v) | RV Therien Structural Polyprotein (SEQ ID NO:8) | 90–96 |
| (vi) | RV Therien Structural Polyprotein (SEQ ID NO:8) | 314–320 |
| (vii) | HIV-1 LV Gag Polyprotein (SEQ ID NO:11) | 145–151 |
| (viii) | HIV-1 LAV-1a Envelope Polyprotein Precursor (SEQ ID NO:14) | 655–661 |
| (ix) | H. influenzae Lipoprotein E Precursor (SEQ ID NO:17) | 99–105 |
| (x) | N. meningitidis Opacity-Related Protein POPM3 (SEQ ID NO:20) | 1–5 |
| (xi) | S. pneumoniae Pneumococcal Surface Protein A (SEQ ID NO:23) | 123–129 |
| (xii)–(xv) | L. monocytogenes Protein P60 Precursor (SEQ ID NO:26) | 151–157; 181–187; 249–255; 292–298 |
(In the retrieved claim text, item (x) recites only AA 1–5, i.e., fewer than the "at least 7 sequential amino acids" stated in the preamble, and the passage contains apparent OCR artifacts — e.g., "amine acid," "Polypretain," "Thorion strain," "A.sub.123." These are likely transcription errors in the source, but per the literal-reading rule I have not corrected them.)
Other independent claims (content inferred from the specification's embodiment language — claim numbers not verified). The written description recites as separate embodiments, which almost certainly correspond to additional independent claims:
- Monoclonal antibody compositions that bind an MRHAS (including the antibody produced by cell line RV-1, ATCC HB 11362), and blocking antibodies defined by their ability to block RV-1 binding.
- A cell line producing such an antibody (RV-1, ATCC HB 11362).
- Pharmaceutical/therapeutic compositions comprising the antibody or the peptide (with carriers/adjuvants).
- Vaccine formulations comprising an immunogenic MRHAS peptide or analogue/mixture.
- Methods of treating or protecting a patient against meningitis by administering the antibody or peptide (blocking a monocyte recognition site for MRHAS).
- An article of manufacture / diagnostic kit — a solid support with a bound peptide of formula a—X—b (X = ≥7 amino acids selected from Table 5), and immunoassay methods for detecting antibodies to meningitis agents using MRHAS peptides, and a method for analyzing a biological fluid for anti-X antibodies.
Explicit uncertainty: I have only the verified verbatim text of claim 1. I do not have authoritative claim-by-claim text for the remaining independent claims or the total claim count, so the overview in the previous paragraph reflects the specification's parallel embodiment language, not confirmed claim language. This should be verified against the USPTO full-text or the patent's printed claims.
Bottom line
US 5,556,757 is a 1993-priority (1995-filed divisional), 1996-issued Insight Biotech patent (Alstyne & Sharma) claiming short "MRHAS" epitope peptides shared between rubella, HIV-1, and the principal bacterial meningitis pathogens (and homologous to monocyte chemokines MCP-1/MCP-3), plus related antibodies, the RV-1 hybridoma (ATCC HB 11362), and diagnostic/therapeutic/vaccine uses. It is long expired. No CAFC 2026 docket activity for this patent was found in the sources available to me, and that negative finding is limited by the search tools used rather than being authoritative.
Sources: https://patents.google.com/patent/US5556757/en ; https://patents.justia.com/patent/5556757
Generated 9/27/2026, 5:13:50 PM
Cases on file (0)
Specific litigation cases in our database that name US patent 5556757. The free-form analysis below may also discuss cases beyond this list.
No cases on file mention this patent. Upload a CSV or add a case manually in Admin → Manage litigation cases.
Litigation summary
Past and pending lawsuits — plaintiffs, defendants, jurisdictions, outcomes, and notable rulings.
I'll search for litigation involving US patent 5556757 across patent litigation databases.
Let me run more targeted searches on litigation-specific databases.
Result: No litigation involving US 5,556,757 found
I searched litigation-oriented sources for the specific patent number US 5,556,757 (US5556757A — "Peptides representing epitopic sites for bacterial and viral meningitis causing agents and their CNS carrier and uses thereof," originally assigned to Insight Biotech Inc). I found no record of any district court, Federal Circuit, ITC, or PTAB litigation naming this patent.
What I searched and what came back
| Search target | Result |
|---|---|
| "5556757" + litigation / lawsuit / patent case | Only the patent's own prosecution/publication pages (Google Patents, Justia, FreePatentsOnline, EveryPatent). No case names. |
| Unified Patents litigation portal (portal.unifiedpatents.com) | No litigation and no inter partes review for this patent number; only unrelated results (e.g., the SightSound '734/'991 family). |
| PACER / docket aggregators (via web) | No docket referencing US 5,556,757. |
| Assignee-focused search ("Insight Biotech" + litigation) | No litigation against third parties; the company appears only in patent-portfolio/prosecution listings. |
| CAFC | No appeal involving this patent. |
Important non-matches (I did not auto-correct these; they are distinct identifiers)
- SightSound.Com Inc. v. N2K, Inc. and related reexamination materials reference US 5,675,734 and US 5,966,440 — those are different patents from the SightSound family, not US 5,556,757.
- JP5556757B2 ("Air conditioner for vehicles") is an unrelated Japanese publication that shares the same digits.
- A Brazilian registration (JUCEC list) and a "Lin Wang" inventor ID both happen to use the number string "5556757"; neither is US patent litigation.
- A Justia query rendered the patent as "5,556,757" with a comma — the same US patent, US5556757A/US08/482,847.
Patent status (context for the absence of litigation)
Per the Google Patents record you supplied:
- Application US08/482,847, filed 1995-06-07; a divisional of application Ser. No. 08/127,499, filed Sep. 28, 1993 (the 1993-09-28 priority date).
- Granted 1996-09-17.
- Legal status: "Expired – Fee Related"; anticipated expiration 2013-09-28.
- Inventors: Diane V. Alstyne, Lawrence R. Sharma; assignee Insight Biotech Inc.
Because the patent expired (anticipated September 28, 2013) and no assertion appears in any of the searched litigation databases, it is highly unlikely the patent was ever asserted in court.
Bottom line
No known litigation involves US 5,556,757. I could not confirm any plaintiff, defendant, jurisdiction, case number, filing date, or outcome because no case appears to exist in the public record.
Confidence caveat: I was limited to the searches run above; I could not directly query PACER or the full Docket Navigator/RPX databases in this session. If you need a definitive negative, the authoritative check is a Docket Navigator or Lex Machina "patent number = 5556757" query across all federal districts, the CAFC, and the ITC, plus a PTAB (P-TACTS) search for the same number — none of which I can verify absolutely here.
Generated 9/27/2026, 5:13:40 PM
Proceedings on file (0)
All PTAB activity →AIA trial proceedings (IPR / PGR / CBM) filed at the USPTO Patent Trial and Appeal Board against this patent. Sourced from the USPTO Open Data Portal and refreshed every six hours; each proceeding number deep-links to the PTAB E2E docket.
No PTAB proceedings on file. This patent has not been challenged via IPR, PGR, or CBM. The absence is itself a signal — well-asserted patents eventually attract IPRs. The LLM analysis below may surface filings the ODP feed hasn’t indexed yet.
PTAB challenges
AIA trial proceedings at the USPTO Patent Trial and Appeal Board — IPR, PGR, and CBM. Petitioners, judge panels, claim-level invalidation outcomes from Final Written Decisions, and Federal Circuit appeals. The single most important defensive datapoint after litigation history.
I'll verify the canonical "no PTAB activity" signal against public sources before writing the analysis.
The canonical block and public sources agree so far. Two more targeted checks to make sure nothing is hiding.
Proceedings overview
Total count: 0 AIA trial proceedings. The canonical structured block ("PTAB proceedings on file") reports that the USPTO Open Data Portal returns no AIA trial proceedings for US 5,556,757, and independent web verification surfaced no IPR, PGR, or CBM naming this patent as the challenged patent. Breakdown by status is therefore not applicable: 0 active, 0 claims invalidated, 0 claims sustained, 0 settled, 0 institution denials. The defensive posture this gives a defendant is not "hardened patent" and not "dead claims" — it is "immune-by-obscurity, but also unlitigated": every claim that issued in 1996 is presumptively intact, yet the patent expired on its anticipated 2013-09-28 date and was never asserted in any forum I could locate, so there is no PTAB record to mine and no estoppel on your side.
Contradiction check against previously generated sections: None. The litigation summary concluded "no known litigation," and the PTAB block states no AIA trials. These are consistent and reinforce each other — a patent that was never asserted in district court is very unlikely to have attracted a defensive IPR, and that is exactly the pattern here. No flag needed.
Proceeding-by-proceeding detail
There are no proceedings to detail. I will not manufacture proceeding numbers, panels, or dispositions. Instead, below is the documented audit trail of how I confirmed the null result, plus the near-miss identifiers that a less careful search would have wrongly reported as hits.
Search-and-verify log for US 5,556,757
| Source type | Query | Result |
|---|---|---|
| Structured prompt data (USPTO ODP) | Patent number = 5556757 | No AIA trial proceedings on file |
| PTAB E2E / PTACTS (via web) | "5556757" IPR petition Patent Trial and Appeal Board |
No petition, institution decision, or FWD referencing this patent |
| Web, cross-referenced to assignee | "Insight Biotech" patent 5556757 IPR |
No IPR; assignee appears only in patent-portfolio/prosecution listings |
| Web, cross-referenced to invalidity practice | "5,556,757" invalidity reexamination Alstyne Sharma meningitis |
No proceeding; returned the patent's own claims text and one academic citation of the patent (Van Alstyne & Sharma, 1996) |
| Federal Circuit / CourtListener (per prior litigation section) | Appeal naming this patent | None |
Important non-matches — do NOT treat these as proceedings on US 5,556,757
These are the traps. Each involves a different patent or a merely cited reference:
- IPR2024-00279, Neurent Medical, Inc. — the petition and its exhibits repeatedly discuss "the '675 patent." That is a different patent (an electroporation/catheter patent, US 10,675,xxx family), not US 5,556,757. Petitioners incorporate arguments under "the '675 Patent" throughout; the number coincidence is the only link.
- IPR2025-00464, Padagis US LLC v. Neurelis, Inc. — the Patent Owner's Exhibit 2039 (a redline of US 11,793,786 to US 11,241,414) lists "5556757 / 12/1995 / Alstyne et al." in a prior-art citation table. This is 5556757 being cited as art against someone else's patent — the opposite of a proceeding against it. It is evidence that the patent's disclosure has residual prior-art value, nothing more.
- US 5,675,734 and US 5,966,440 (SightSound family) — same digits in different order; already flagged in the litigation section. Not this patent.
- JP5556757B2 ("Air conditioner for vehicles") — unrelated Japanese publication. Not this patent.
- JUCEC Brazilian registration "5556757" and inventor ID "5556757" (Lin WANG, Jinan City, CN) — administrative identifiers, not patent proceedings.
Strategic summary
Claim status: all claims UNTESTED. Because no AIA trial was ever instituted, no claim of 5,556,757 has been canceled, narrowed, or confirmed by the PTAB. Every claim that issued on 1996-09-17 stands exactly as granted. From the printed claim set, the operative claims appear to be claim 1 (a peptide of formula a–X–b, where X is at least seven sequential amino acids of a Meningitis Related Homologous Antigenic Sequence selected from seventeen enumerated alternatives spanning rubella structural polyprotein, HIV-1 gag and envelope polyproteins, H. influenzae lipoprotein E precursor, N. meningitidis opacity-related protein POPM3, S. pneumoniae PspA, L. monocytogenes P60 precursor, and the chemokines hMCP-1 and hMCP-3) and claim 2 (an article of manufacture comprising a solid support with a claim-1 peptide bound to it). Caveat: I verified claims 1 and 2 from the published claim text, but I did not independently confirm that claim 2 is the terminal claim; treat the "all claims untested" conclusion as applying to the claim set as a whole regardless of its exact size.
The practical significance cuts both ways. On one hand, there is no FWD to hand a judge or an opposing counsel, no canceled claim to render a demand letter frivolous, and no claim-construction ruling from the Board to adopt. On the other hand, the patent's own expiration on 2013-09-28 means the only relief theoretically available today would be past damages for infringement occurring on or before that date (subject to the six-year § 286 damages lookback, which from 2026-09-27 would reach back only to 2020-09-27 — entirely after expiration). In other words, even a fully intact claim 1 is now practically unenforceable for damages: the § 286 window and the expiration date do not overlap. That is a far stronger defensive point than any IPR outcome could have given, and it should be the first sentence of any response to a demand letter.
Estoppel landscape: § 315(e)(2) estoppel is entirely absent. Because no petitioner ever filed, no petitioner (or privy or real party in interest) is barred from raising any ground. There are no unavailable prior-art grounds attributable to PTAB activity — the full universe of § 102/§ 103 art, plus § 112 (written description, enablement, indefiniteness) and § 101 challenges, remains open in a district court or ITC forum. Note the mirror-image consequence: § 315(b)'s one-year bar and § 311(b)'s patents-and-printed-publications limitation are irrelevant to you, so you are free to use system art, public use, and on-sale evidence in court — categories an IPR could never have reached anyway. Given the 1993-09-28 priority date and a 1996 grant, the prior-art field is deep and old; the seventeen-sequence Markush-style group in claim 1 is also unusually vulnerable to § 112 written-description and indefiniteness attack for over-breadth.
Pattern signals: none. There is no repeat petitioner (no petitioner at all), no aggressive Patent Owner appeal practice at the Federal Circuit, and no defensive aggregator in the chain — Unified Patents' portal shows no activity for this patent number. Insight Biotech Inc. never appears as a PTAB petitioner or patent owner in any trial I could locate. This is the profile of a dormant academic/biotech-era patent whose assignee never commercialized or asserted it, not the profile of a monetized portfolio.
Recommended next steps
If you are a defendant, the answer is that there is no PTAB ground to stand on — and you do not need one:
- Lead with expiration, not invalidity. The patent's anticipated expiration was 2013-09-28 (per the Google Patents legal-status record). Any damages claim is limited by 35 U.S.C. § 286 to six years before filing; a suit filed on or after 2020-09-28 cannot reach a single day of the patent's enforceable term. Confirm the expiration/maintenance-fee history directly on USPTO Patent Center (application US08/482,847) — the record shows legal status "Expired – Fee Related," which raises the possibility the patent lapsed early for non-payment of maintenance fees, potentially pushing the enforceable period even shorter. That is worth pinning down to the day.
- There is no FWD to cite. Do not represent to a court or adversary that any claim of 5,556,757 has been invalidated, canceled, or adjudicated at the PTAB — it has not. The correct, defensible statement is: "No AIA trial proceeding has ever been instituted against US 5,556,757; no claim has been canceled or confirmed by the Board."
- If you nonetheless need an invalidity theory (e.g., for a declaratory-judgment posture, or because the demand letter also invokes a related patent), the absence of any § 315(e)(2) estoppel means the field is wide open. Best candidates, in order: § 112 indefiniteness/enablement against the seventeen-member sequence group in claim 1; § 102/§ 103 over the very references the patent itself cites (Muesing 1985, Wain-Hobson 1985, Yother 1992, Köhler 1990, Green 1992, Van Damme 1992) for the individual seven-mer sequences; and § 101 for claim 2's solid-support article if asserted in a diagnostic-kit theory.
- If you want a PTAB filing anyway, note the timeliness trap. IPRs against expired patents are permitted, but the Board construes expired claims under the Phillips standard and, more importantly, an IPR filed now would be a 2026 petition against a patent that expired in 2013 — almost certainly a discretionary-denial target under the current Magnolia Medical line of Director-level guidance discouraging institution where review would not efficiently resolve a live dispute. Do not spend the ~$250K to FWD without first resolving whether any assertable claim term remains.
- For a definitive negative, run an authoritative "patent number = 5556757" query across Lex Machina or Docket Navigator (all districts, CAFC, ITC) and PTAB P-TACTS / E2E for the same number, plus a Patent Center maintenance-fee/expiration check. I could not execute direct authenticated queries against those systems in this session, so this null result rests on the structured ODP block plus the web verification above and should be confirmed at the source before being represented as final.
Bottom line for the record: US 5,556,757 has zero AIA trial proceedings on file. Its claims are intact but its term has run. The defensive play is not an IPR — it is a calendar.
Generated 9/27/2026, 5:14:05 PM
Assignment history
Inventors, original assignee, and the chain of ownership recorded with the USPTO — including the correspondent attorney who recorded each assignment, since shell-LLC chains often share one repeat-player attorney even when the entity names look unrelated. Surfaces NPE / patent-troll patterns: shell-entity transfers, known asserters in the chain, repeat correspondent fingerprints, pre-litigation assignments, and bankruptcy fire-sales.
I'll investigate the assignment record for US 5,556,757. Let me search USPTO Assignment Center and related sources.
Assignment record for US 5,556,757 — findings
Verification caveat up front: I do not have live API access to the USPTO Assignment Center in this session; I could only reach it indirectly through web search. The evidence I do have is the authoritative Google Patents record you supplied, which enumerates the patent's legal events, plus third-party bibliographic mirrors (Justia, FreePatentsOnline). On that evidence, no post-issuance assignment was recorded for this patent — but I flag this as a strong inference, not a verified Assignment Center query result. The single authoritative check is a patent number = 5556757 query at https://assignment.uspto.gov/patent/index.html (or https://assignmentcenter.uspto.gov/).
Inventors
| Inventor | Location of record | Employer at filing |
|---|---|---|
| Diane V. Alstyne | Vancouver | Not independently confirmable; assignee of record is Insight Biotech / Biotek (see note) |
| Lawrence R. Sharma | Vancouver | Not independently confirmable; same |
- Both inventors are listed at "Vancouver" in the Justia Patent History entry for this patent (no state/province given — it does not resolve to Vancouver, WA vs. Vancouver, BC).
- Inventor background detail worth noting: the specification cites Singh & Van Alstyne, 1978, Brain Res. 155:418-421, Pope & Van Alstyne, 1981, Virology 124:173-180, and Van Alstyne & Paty, 1983, Virology 124:173-180 — i.e., Alstyne had a prior academic publication record on rubella virus replication in CNS/glial cells well before the 1993 priority date. That is consistent with a research-lab founder profile rather than a typical corporate R&D employee, but it is not evidence of employment, and I will not infer an employer from it.
- Unusual-pattern check: I found no evidence of inventors departing the assignee within 12 months of filing, nor of any inventor-side assignment activity. There is nothing in the record to support (or refute) a pre-fire-sale departure pattern.
Naming discrepancy to flag (do not auto-correct): the authoritative Google Patents text names the assignee "Insight Biotech Inc"; Justia renders it "Insight Biotek, Inc. (St. Michaels)." These are very likely the same entity with an alternate spelling, but I am treating them literally and flagging the difference rather than merging them.
Original assignee
Insight Biotech Inc (Google Patents: original assignee and current assignee) / Insight Biotek, Inc., St. Michaels (Justia).
- Product embodying the claims: No evidence found that the assignee ever shipped a commercial product reading on claim 1. The claimed subject matter is a genus of 7-mer epitope peptides plus an immunoassay article of manufacture (claim 2); the closest thing to a product in the record is the RV-1 hybridoma, ATCC HB 11362, deposited 1993-05-26 — a research reagent, not a marketed diagnostic kit.
- Primary line of business: Appears to be a small research/diagnostics biotechnology concern (monoclonal antibody and peptide reagents), based at St. Michaels, Maryland per Justia. I could not locate a current corporate website, SEC registrant record, or active product catalog.
- Current status: Unknown / likely defunct or dormant. The patent lapsed for fee non-payment with an anticipated expiration of 2013-09-28, and Google Patents records the status as "Expired – Fee Related." A patent-holding entity that stops paying maintenance fees on its only identifiable asset family is ordinarily not an operating concern. I explicitly decline to state whether Insight Biotech/Biotek was dissolved, acquired, or is dormant — I have no filing to cite.
- Prosecution counsel of record: Foley & Lardner (per Justia "Law Firm"). Note carefully: this is the prosecuting firm, not an assignment correspondent. The task's correspondent field refers to whoever recorded an assignment with the USPTO — and since there is no recorded assignment, there is no assignment correspondent to report.
Assignment timeline
No assignments are recorded in the sources available to me. The Google Patents legal-events block you supplied lists only: 1995-06-07 application filed by Insight Biotech Inc; 1995-06-07 priority to US08/482,847; 1996-09-17 application granted; 1996-09-17 publication of US5556757A; 2013-09-28 anticipated expiration. None of those events is a conveyance. Google Patents' "Current Assignee" field further resolves to the same entity as the "Original Assignee" — the behavior it exhibits when no reassignment data exists.
Accordingly: there is no chain to reconstruct. The only presumptive conveyance is the original inventor→assignee assignment that gave Insight Biotech/Biotek standing to have the patent issue in its name — but even that instrument is not visible to me (no reel/frame, no execution date, no correspondent). I am not going to invent one. If the Assignment Center does surface an original-recordation entry, it will most likely be a single 1993–1995-era frame with Foley & Lardner or the assignee's in-house correspondent named, and nothing thereafter.
Timeline diagram
timeline
title Ownership of US 5556757
1993 : Priority date 28 Sep
: Parent app 08 127 499 filed
1995 : Divisional 08 482 847 filed 7 Jun
1996 : Patent granted 17 Sep
: Assignee Insight Biotech Inc
2013 : Lapsed for fee non payment
NPE / troll-pattern signals
| # | Signal | Call | Basis |
|---|---|---|---|
| 1 | Shell-entity transfer | Not present | No assignment recorded at all; assignee of record is the original operating entity, not an "IP/Holdings/Ventures" successor. No LLC name, no registered-agent address, no Delaware/Texas single-member entity anywhere in the record. |
| 2 | Known asserter in the chain | Not present | Neither assignee name — Insight Biotech Inc nor Insight Biotek, Inc. — appears on the Acacia / Marathon / IV / IPNav / Wi-LAN / Conversant / Vringo / Pendrell / Innovatio / MPHJ / Lumen View / Round Rock / Spangenberg lists, or on any Unified Patents / RPX high-frequency-plaintiff roster I can locate. No other assignee exists to compare. |
| 3 | Repeat correspondent across the chain | Unclear / not applicable | There is no chain. The only counsel of record is Foley & Lardner, which appears in its prosecution capacity, not as an assignment correspondent on any reel/frame. A single appearance on a single patent is expressly not a finding under the stated rule, and here there is not even a single assignment appearance. |
| 4 | Cascading transfers | Not present | Zero recorded transfers; nothing to cascade. No shared correspondent address, no common-principal LLCs. |
| 5 | Pre-litigation transfer | Not present | The prior section of this analysis found no litigation naming US 5,556,757 in any district court, the Federal Circuit, the ITC, or the PTAB. With no first-filed suit, there is no anchor date for a pre-litigation transfer, and no transfer was recorded anyway. |
| 6 | Bankruptcy fire-sale | Unclear | I cannot confirm or exclude a bankruptcy of Insight Biotech/Biotek; I found no Chapter 7/11 docket or asset-sale notice referencing this patent. Critically, there is no recorded purchaser — so even if the assignee failed, this patent was not sold through a recorded proceeding. |
| 7 | Privateering | Not present | No operating-company→NPE transfer exists, and no asserting NPE exists to have been armed. The patent lapsed unsold and unasserted. |
| 8 | Defensive aggregator | Not present | Chain does not terminate at RPX, AST, LOT, Unified, or OIN. It terminates at the original assignee, then at the public domain via fee lapse. |
Verdict
Insufficient data (no records, or only the original assignment).
The evidence supports nothing stronger. The Google Patents record lists no conveyance event between the 1995-06-07 filing and the 2013-09-28 anticipated expiration, and its "Current Assignee" resolves to the "Original Assignee" (Insight Biotech Inc) — the signature of an unassigned patent. There is no reel/frame to cite, no correspondent to pattern-match, and no litigation (per the prior section) to anchor a pre-suit-transfer analysis. Every NPE signal that could be affirmatively triggered requires an assignment that does not appear to exist; the residual "unclear" calls (bankruptcy, current corporate status of the assignee) are gaps in coverage, not findings, and I will not convert them into an NPE call absent a reel/frame.
Verify at: https://assignment.uspto.gov/patent/index.html ← search 5556757, then confirm against https://assignmentcenter.uspto.gov/. If that query returns a single 1990s-era original assignment only, this verdict stands as non-asserting, never-monetized, expired — the ordinary profile of a small biotech's lapsed patent, not a troll chain.
Generated 9/27/2026, 5:14:09 PM
Prior art
Earlier patents, publications, and products that may anticipate or render the claims unpatentable.
I'll run targeted searches for the cited prior art on this patent.
Let me dig into the specific citation records for this patent.
Good — I found the Justia citation record. Let me confirm whether any patent documents (as opposed to NPL) were cited, and check Google Patents' citation lists.
Search result: identification of US 5,556,757
Confirmed match (the only record with this exact number):
| Field | Value |
|---|---|
| Patent | US 5,556,757 (US5556757A) |
| Title | "Peptides representing epitopic sites for bacterial and viral meningitis causing agents and their CNS carrier and uses thereof" |
| Application | US 08/482,847 (divisional of 08/127,499, filed 1993‑09‑28) |
| Filing / Issue | 1995‑06‑07 / 1996‑09‑17 |
| Inventors / Assignee | Diane V. Alstyne; Lawrence R. Sharma / Insight Biotech Inc (FPO lists "Insight Biotek, Inc.") |
| Status | Expired – Fee Related (anticipated expiration 2013‑09‑28) |
Note on tooling: I could not run a native USPTO PatentCenter / Patent Full‑Text (PatFT) query in this session. I reconstructed the citation record from the Google Patents record, the Justia patent page (which reproduces the printed front‑page citation list), and FreePatentsOnline's copy of the claim text. Treat the list below as mirror‑sourced, not as a direct USPTO print.
Explicit non‑matches (per the literal‑identifier rule, not corrected): JP5556757B2 (vehicle air conditioner), a JUCEC (Brazil) registration "5556757", an IEEE DOI 10.1109/ICCCE.2010.5556757, and a Patents‑Review inventor ID 5556757 (Lin Wang). None is US 5,556,757.
Principal finding on the "patent citations" question
US 5,556,757 has no U.S. patent‑document citations on its face.
Every reference recovered from its citation record is non‑patent literature (NPL) — journal articles, book chapters, and one sequence database entry. The Justia record for this patent shows a "Referenced Cited" block containing only an "Other references" list; no "Patent Citations" (U.S. Patent Documents) block appears. Consequently there are no §102(b)/§102(e) anticipations available from cited U.S. patents, because none were cited.
This is unusual but consistent with the subject matter: the invention is a 1993‑priority peptide/epitope invention, and the closest art was in the virology/bacteriology literature rather than the patent literature.
I must flag the counter‑consideration: the copy of the patent text supplied in the earlier sections of this analysis (fetched from Google Patents) did not include any front‑page "(56) References Cited" section at all — the fetch began at the "Definitions"/description. So the list below comes from the Justia reproduction and is likely truncated (it visibly cuts off mid‑entry at "Rollins et al…"). There may be additional cited references I could not see.
Cited references (all NPL) — citation, date, description, and §102 analysis
The right‑hand column identifies which claim element a reference would have to disclose to anticipate. Recall that claim 1 requires a peptide a—X—b where X is ≥7 contiguous residues at a specific positional correspondence to a named SEQ ID NO in a named parent protein, plus a/b termini (1–8 native flanking residues or a coupling substituent); claim 2 is the article of manufacture (solid support + claim‑1 peptide).
Group A — references that disclose the parent protein sequences from which the claimed blocks are taken (the only §102‑capable references):
| # | Full citation | Date | What it discloses | Claim(s) potentially anticipated |
|---|---|---|---|---|
| 1 | Muesing et al., "Nucleic acid structure and expression of the human AIDS/lymphadenopathy retrovirus," Nature 313:450‑458 | 1985 | Complete nucleotide/derived amino‑acid sequence of the HIV‑1 (LV) gag polyprotein (478 aa) | Claim 1, item (vii) (AA145–151 of SEQ ID NO:11) on an inherency theory |
| 2 | Stern & Meyer, "Common mechanism controlling phase and antigenic variation in pathogenic neisseriae," Mol. Microbiol. 1:5‑12 | 1987 | N. meningitidis opacity‑related (opa) protein sequences, incl. the POPM3 protein (170 aa; SEQ ID NO:20 in the patent) | Claim 1, item (x) (AA1–5 of SEQ ID NO:20) |
| 3 | Yother & Briles, "Structural Properties and Evolutionary Relationships of PspA…," J. Bacteriol. 174:601‑609 | 1992 | Complete sequence of S. pneumoniae pneumococcal surface protein A (SEQ ID NO:23) | Claim 1, item (xi) (AA123–129) |
| 4 | Kohler et al., "The Gene Coding for Protein p60 of Listeria monocytogenes…," Infect. Immun. 58:1943‑1950 | 1990 | Sequence of the L. monocytogenes P60 precursor / iap (484 aa; SEQ ID NO:26) | Claim 1, items (xii)–(xv) (AA151–157, 181–187, 249–255, 292–298) |
| 5 | Green et al., EMBL Bank (database entry) | 1992 | H. influenzae outer‑membrane lipoprotein E precursor (p4; 274 aa; SEQ ID NO:17) | Claim 1, item (ix) (AA99–105) |
| 6 | Yoshimura et al., "Human monocyte chemoattractant protein‑1 (MCP‑1)," FEBS Lett. 244:487‑493 | 1989 | Human MCP‑1 sequence | Claim 1, item (xvi) (AA93–99 of hMCP‑1, SEQ ID NO:35) |
| 7 | Robinson et al., "Complete amino acid sequence of a human monocyte chemoattractant…," PNAS USA 86:1850‑1854 | 1989 | Complete hMCP‑1 (MCP‑1/JE) amino‑acid sequence | Claim 1, item (xvi) |
| 8 | Rollins et al., Mol. Cell. Biol. 9:4687‑4695 | 1989 | Resting‑monocyte chemokine (MCP‑1/JE) expression | Claim 1, item (xvi) (weaker — expression/regulation, not necessarily full sequence) |
| 9 | Michiel et al., "Chemokines: The Missing Link," Bio/Technology 11:739 | 1993 | Review of chemokine family sequences/structure | Claim 1, items (xvi)–(xvii) (background; review, not primary sequence disclosure) |
Group B — references cited as background on the disease, pathogens, and diagnostics (no §102 anticipation of the peptide claims):
| Full citation | Date | Description | §102 relevance |
|---|---|---|---|
| Roos, "Chapter 16," in Scheld et al. eds., Infections of the Central Nervous System 335‑403 | 1991 | Clinical/pathologic review of meningitis | Background only; no peptide |
| Herrmann, "Rubella Virus," in Diagnostic Procedures for Viral, Rickettsial and Chlamydial Infections 725‑766 | 1979 | RV serology / HA‑inhibition | Background only |
| Spalding, "In Hot Pursuit of an HIV Vaccine," Bio/Technology 10:24‑29 | 1992 | HIV vaccine candidate peptides (gp120/160/41, p17, p14) | Background; does not disclose the MRHAS 7‑mers |
| Griffiss et al., "Vaccines Against Encapsulated Bacteria…," Rev. Infect. Dis. 9:176‑188 | 1987 | Polysaccharide vaccine review | Background |
| Terry et al., "Localization of the rubella E1 epitopes," Arch. Virol. 98:189‑197 | 1988 | Three non‑competing Mabs to RV E1 | Background; E1, not the claimed core/E2 blocks |
| Connolly et al., "Carotid Artery Thrombosis, Encephalitis, Myelitis and Optic Neuritis…," Brain 98:583‑594 | 1975 | RV neuropathology | Background |
| Pope & Van Alstyne, "Evidence for Restricted Replication of Rubella Virus in Rat Glial Cells in Culture," Virology 113:776‑780 | 1981 | RV restricted replication in glia | Inventors' own publication → possible §102(b) bar (>1 yr pre‑priority) but no peptide disclosure |
| Van Alstyne & Paty, Virology 124:173‑180 | 1983 | db‑cAMP reversal of RV restriction in glia | Same as above |
| Voller & Bidwell, "A Simple Method for Detecting Antibodies to Rubella," Br. J. Exp. Pathol. 56:338‑339 | 1975 | ELISA methodology | Background; supplies solid‑support element but not the claimed peptide |
| Parkman, Meyer et al., "Attenuated Rubella Virus," NEJM 275:569‑580 | 1966 | Live attenuated RV vaccine | Background |
| Stephens et al., "Equine Infectious Anemia Virus gag and pol Genes…," Science 231:589‑594 | 1986 | Lentiviral gag/pol relatedness | Background |
| Ho et al., "Primary Human T‑Lymphotropic Virus Type III Infection," Ann. Intern. Med. 103:880‑883 | 1985 | Acute HIV‑1 syndrome incl. lymphocytic meningitis | Background |
| Fraser et al., Am. J. Epidemiol. 100:29‑34 | 1974 | Hib meningitis epidemiology | Background |
| Tunkel et al., "Bacterial Meningitis: Recent Advances…," Ann. Intern. Med. 112:610‑623 | 1990 | Bacterial meningitis pathophysiology/treatment | Background |
| Goebel et al., "Studies on the Pathogenicity of Listeria monocytogenes," Infection 19:S195‑197 | 1991 | Listeria pathogenesis | Background |
| Michel & Cossart, "Physical Map of the monocytogenes Chromosome," J. Bacteriol. 174:7098‑7103 | 1992 | Listeria genetics | Background |
| Cordy, "Pathomorphology and Pathogenesis of Bacterial Meningoventriculitis of Neonatal Ungulates," Vet. Pathol. 21:587‑591 | 1984 | Bacterial CNS entry via monocytes | Background — but it is the rationale for the MRHAS/monocyte hypothesis |
(The recovered list ends mid‑entry at "Rollins et al…" and is likely incomplete. The specification body additionally cites — but I could not confirm as front‑page citations — Wain‑Hobson et al., Cell 40:9‑17 (1985) [HIV‑1 LAV‑1a envelope precursor, SEQ ID NO:14]; Clarke et al., NAR 15:3041‑3057 (1987), Dominguez et al., Virology 177:225‑238 (1990) and Zheng et al., Arch. Virol. 98:189‑197 (1988) [RV structural polyprotein, SEQ ID NOS 1 and 8]; Ratner et al., Nature 313:277‑280 (1985) [HIV‑1 genome]; and van Damme et al., J. Exp. Med. 176:59‑65 (1992) [MCP‑3, SEQ ID NO:38]. Those four are the references that would map onto claim‑1 items (i)–(vi), (viii) and (xvii) if they are indeed on the face of the patent.)
Which claims could a cited reference actually anticipate under §102?
Applying §102 strictly, only Group A is capable of anticipation, and only on a theory that disclosure of the full‑length parent protein inherently describes each recited shorter block:
- Claim 1 is the only claim arguably reachable. Each of items (vii)–(xvi) corresponds to a block embedded in a protein whose complete sequence was published by the cited reference (Muesing 1985; Stern & Meyer 1987; Yother & Briles 1992; Kohler 1990; Green EMBL 1992; Yoshimura/Robinson 1989). For those items the anticipation argument is straightforward: a reference describing a 478‑aa or 484‑aa polypeptide literally describes its continuous 7‑mers.
- Claim 2 is not anticipated by any single cited reference. It adds "a solid support and, having bound to said support, a peptide…" — no cited sequence reference discloses an immobilized MRHAS peptide. Voller & Bidwell supplies the support concept but no MRHAS sequence; the sequence references supply the sequence but no support. No single reference contains all elements.
Countervailing points that materially weaken every §102 theory above (be explicit about these):
- Date gap. The claims carry a 1993‑09‑28 priority. Under pre‑AIA §102(b) the critical date is 1992‑09‑28. Michiel (1993) and Green's EMBL entry (1992) sit at or after that line, so they are at best §102(a)/(e)‑style art, or not prior art at all if the invention was earlier.
- Claim breadth runs the other way. Claim 1 recites "at least 7 sequential amino acids and conservative substitutions or modifications thereof." That is a genus, so §102 anticipation of the whole claim by a reference disclosing a single species is not automatic; the classic large‑genus/anticipation doctrine (cf. In re Petering / In re Baird line of reasoning) cuts against a clean §102 rejection of the full claim scope.
- The preamble limitation. Claim 1 requires that X be "contained in … a protein or peptide found in a bacterium or virus that is an etiologic agent of meningitis, said protein or peptide is a chemokine involved in cell chemotaxis." That internally contradictory limitation (a bacterial/viral protein that is also a chemokine) is not satisfied by any cited reference as written, and would have to be resolved by claim construction before any §102 mapping is meaningful.
- Internal claim inconsistency. Item (x) recites only AA1–AA5 of the N. meningitidis POPM3 protein (SEQ ID NO:20) — five residues — despite the "at least 7 sequential amino acids" requirement in the claim body. Item (xi) is also garbled in the source as "A.sub.123 to AA.sub.129." Any §102 mapping onto items (x)/(xi) is unreliable until this is reconciled.
- Examiner vs. applicant citation. I could not determine which of these were the examiner's rejections versus the applicant's IDS. That distinction matters, because an examiner‑cited reference is more likely to have been considered §102‑relevant.
Contradiction to flag against the earlier "Patent summary" section
The prior summary stated claim 1's recited group runs (i)–(xv) and that the chemokine sequences appear only in the tables (SEQ ID NOS 35/37/38/40). The actual printed claim 1 text (Justia and FreePatentsOnline) recites items (xvi) and (xvii):
- (xvi) the amino‑acid sequence of a variant of hMCP‑1 corresponding to AA93–AA99 of hMCP‑1 as set forth in SEQ ID NO:35;
- (xvii) the amino‑acid sequence of the chemokine hMCP‑3 corresponding to AA61–AA67 of hMCP‑3 as set forth in SEQ ID NO:38.
So the claim group is (i)–(xvii), i.e., 17 items, not 15, and the chemokines are inside claim 1 rather than only in the tables. This is a genuine contradiction; the claim text should govern. The earlier summary's "explicit uncertainty" about claim numbering is also partly resolved: claim 2 is confirmed as the article‑of‑manufacture claim ("a solid support and, having bound to said support, a peptide having a formula aXb according to claim 1"). The total claim count is still unverified.
Two smaller cross‑references: the earlier summary's note that item (x) recites only AA1–5 is confirmed; and the "Thorion strain," "Polypretain," "amine acid" spellings are reproduced in both FPO and Justia, so they appear to be errors in the printed patent (or a shared OCR layer), not artifacts of one source.
Bottom line
- The patent is confirmed as US 5,556,757 / US5556757A, App. 08/482,847 — distinct from JP5556757B2, the Brazilian "5556757" registration, and the IEEE DOI.
- It cites no U.S. patent documents. All cited prior art is NPL, so there is no patent‑document §102 citation to analyze — the answer to "each patent citation" is, literally, that there are none in the recovered record.
- The only §102‑capable cited references are the sequence‑disclosure papers mapping onto claim‑1 items (vii)–(xvi): Muesing 1985 (HIV‑1 gag), Stern & Meyer 1987 (N. meningitidis opa/POPM3), Yother & Briles 1992 (S. pneumoniae PspA), Kohler et al. 1990 (L. monocytogenes p60), Green et al. EMBL 1992 (H. influenzae lipoprotein E), and Yoshimura/Robinson/Rollins 1989 (hMCP‑1). Each could, on an inherency theory, be urged against claim 1 only. No cited reference anticipates claim 2, and none anticipates the antibody/hybridoma/vaccine/method claims.
- Caveats that limit all of the above: the Justia citation list is truncated, I could not query PatentCenter directly, and I could not separate examiner citations from applicant IDS citations.
Confidence: high on the bibliographic identification and on the "no patent documents cited" conclusion as reflected in the recovered mirrors; moderate‑to‑low on the completeness of the citation list and on any specific §102 mapping, which requires the printed front page and the full claim set.
Generated 9/27/2026, 5:14:46 PM
Obviousness
Combinations of prior art that suggest the claimed invention would have been obvious under 35 U.S.C. § 103.
I'll gather the prior-art context available for this patent before drafting the § 103 analysis.
Let me check the patent family, citations, and the later patents that cite this one.
Let me confirm the family relationships and probe for the closest cross-reactive-epitope prior art.
Obviousness Analysis — US 5,556,757 under 35 U.S.C. § 103
A. Threshold note on the "Prior Art" material actually available
I have to flag a gap before giving conclusions. The page text supplied to me for this patent contains no examiner search report and no front‑page "(56) References Cited" list — those sections did not render in the fetched content. What the supplied text does contain is the specification's own "Background of the Invention," which cites roughly two dozen items, plus the enumerated sequence‑listing windows and Tables 1–5. Accordingly:
- I treat the references cited by the applicant in the specification as the closest art of record (an applicant's own citations are admissions of what was known).
- I supplement with references I could retrieve by search.
- I could not verify the examiner's actual (56) list, so I cannot confirm which references the USPTO itself considered. Treat the grounds below as a hypothetical/defensive § 103 analysis, not a reproduction of any real Office action.
Consistent with the earlier sections of this analysis, I found no litigation, IPR, or CAFC proceeding involving this patent — so there is no real-world obviousness record to work from.
B. Governing standard
Graham v. John Deere Co., 383 U.S. 1 (1966) (scope/content, differences, PHOSITA level, secondary considerations), as modified by KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007). Under KSR, a combination is obvious where there is an "articulated reasoning with a rational underpinning," including when the art presents a finite number of identified, predictable solutions, when a known technique is applied to a known problem, or when the invention is merely "obvious to try." PHOSITA here: a PhD-level immunologist/virologist with 2–5 years' experience in monoclonal antibody production, peptide immunochemistry, and sequence analysis circa 1993.
C. Claim scope to be analyzed (and two internal discrepancies to flag)
The verified verbatim language is claim 1 (peptide of formula a—X—b, X = ≥7 aa selected from items (i)–(xv), each defined by positional correspondence to a published reference sequence). The remaining independent claims (antibody, hybridoma, pharma/vaccine compositions, methods of treatment, solid-support article, immunoassays) were reconstructed from the specification's parallel embodiment language in the earlier section — I still lack confirmed text for them.
Two contradictions between the earlier-generated summary and the family's own Tables (flagging, not correcting):
| Item | Earlier summary said | Sibling US5510264 Table 5 / Table 4 says |
|---|---|---|
| (xi) S. pneumoniae pspA | residues 123–129 | residues 423–429, sequence QQQPPKA |
| (iii) RV M33 313–319 | PPQPPCA (SEQ ID NO:7) |
Table 4 lists two entries at 313–319: PPQPPRA and LPQPPCA |
The specification body of US 5,556,757 does say "RV1 Mab antigens are QPQPPRM SEQ ID NO:3 and PPQPPCA SEQ ID NO:7," which is consistent with the LPQPPCA variant, not PPQPPRA. These inconsistencies matter for prior-art mapping and should be resolved against the printed patent before any rejection is finalized.
D. The prior art available before the 1993-09-28 priority date
| # | Reference | What it discloses | Relevance |
|---|---|---|---|
| PA-1 | Clarke et al., 1987, Nucl. Acids Res. 15:3041‑3057; Zheng et al., 1988, Arch. Virol. 98:189‑197; Dominguez et al., 1990, Virology 177:225‑238 (all cited in spec) | Complete RV structural polyprotein sequences for M33, Therien, Judith, HPV77 | Discloses the entire sequence context of items (i)–(vi), including QPQPPRM, QTPAPKP, PPQPPRA/LPQPPCA |
| PA-2 | Muesing et al., 1985, Nature 313:450‑458; Wain‑Hobson et al., 1985, Cell 40:9‑17 (cited in spec) | HIV‑1 LV gag polyprotein (478 aa) and LAV‑1a envelope polyprotein (861 aa) | Discloses QAISPRT (gag 145‑151) and QNQQEKN (env 655‑661) |
| PA-3 | Green et al., 1992, EMBL Bank (cited in spec) | H. influenzae Lipoprotein E Precursor / p4 (274 aa) | Discloses QVQNNKP (99‑105) |
| PA-4 | Stern, 1987, Mol. Microbiol. 1:5‑12 (cited in spec) | N. meningitidis Opacity‑Related Protein POPM3 (170 aa) | Discloses IQPPKN (1‑5) and the 13‑mer IQPPKNLLFSSLL |
| PA-5 | Yother, 1992, J. Bacteriol. 174:601‑609 (cited in spec) | Complete S. pneumoniae pspA sequence | Discloses QQQPPKA |
| PA-6 | Koehler et al., 1990, Infect. Immun. 58:1943‑1950; Bubert et al., 1992, J. Bacteriol. 174:8166‑8171 (cited in spec) | L. monocytogenes P60/iap precursor (484 aa), plus hydrophilicity/secondary-structure analysis showing the middle region is surface-exposed | Discloses all four Listeria windows; affirmatively teaches which region is immunologically accessible |
| PA-7 | Yoshimura et al. 1989 / Rollins et al., 1989, Mol. Cell. Biol. 9:4687‑4695 / Furutani et al. 1989 (cited in spec); Van Damme et al., 1992, J. Exp. Med. 176:59‑65 (cited in spec) | Sequences of MCP‑1 (hJE/GDCF‑2) and MCP‑3 | Discloses QTQTPKT (MCP‑1 93‑99) and KTQTPKL (MCP‑3 61‑67) |
| PA-8 | Kohler & Milstein, 1975, Nature 256:495‑496; Goding, 1980/1986 (cited in spec) | Hybridoma/mAb production | Routine route to any mAb, including RV1 |
| PA-9 | Terry et al., 1988, Arch. Virol. 98:189‑197; Ho‑Terry et al., 1986, Arch. Virol. 87:219‑228 (cited in spec) | Three non‑competing mAbs against RV E1; RV protein/epitope characterization | Expressly establishes RV mAbs and epitope mapping as known |
| PA-10 | Stewart & Young, 1984, Solid Phase Peptide Synthesis; Tam et al., 1983, J. Am. Chem. Soc. 105:6442 (cited in spec) | Solid-phase peptide synthesis | Makes any recited 7‑mer a routine synthetic target |
| PA-11 | Voller & Bidwell, 1975, Br. J. Exp. Pathol. 56:338‑339; Towbin et al., 1979, PNAS 76:4350‑4354; and U.S. Pat. Nos. 3,817,827; 3,850,752; 3,901,654; 3,935,074; 3,984,533; 3,996,345; 4,034,074; 4,098,876 (all cited in spec) | ELISA, immunoblotting, and labeled‑immunoassay formats | Supplies every element of the diagnostic/kit/method claims |
| PA-12 | Cordy, 1984, Vet. Pathol. 21:593‑597 (cited in spec) | Bacteria carried into CSF in association with monocytes migrating into the CSF compartment | Supplies the mechanistic motivation to implicate monocyte chemoattraction |
| PA-13 | Waterman, 1986, Nucl. Acids Res. 14:9095; Hitachi HIBIO MacDNASIS manual (cited in spec) | Computer‑assisted sequence alignment/homology search | Makes the homology‑screening step routine |
| PA-14 | Michiel, 1993, Bio/Technology 11:739 (cited in spec) | Review of chemokine structure/function | Motivates comparison of pathogen sequences to chemokines |
Not prior art: US 5,510,264 (the parent, App. 08/127,499 — same inventive entity, not "by another" under § 102(e)); US 8,071,102 (App. 09/489,850, 2011); US 7,972,597 and EP 2,298,717 (both post-date and in fact adopt the "MCP MRHAS motif" from this family). These are context only.
E. Grounds of rejection
Ground 1 — Each recited X is a literal contiguous subsequence of a published protein; making it was routine
Combination: PA‑1 (or PA‑2, PA‑3, PA‑4, PA‑5, PA‑6, PA‑7) in view of PA‑10 and PA‑11.
A reference that discloses a protein's complete amino acid sequence discloses every contiguous subsequence of it. Items (i)–(xv) are not new compositions at all — they are 5‑ to 7‑residue excerpts of proteins whose sequences were in print years earlier (PA‑1 through PA‑7). The claimed "peptides of formula a—X—b" are therefore structurally identical to naturally occurring fragments, and the claim's own definition of a and b (an amino terminus; a carboxy terminus; or 1–8 native flanking residues) means the claim reads on the natural fragments themselves, not merely on synthetic constructs.
- In re Kratz, 592 F.2d 1169 (CCPA 1979) — a claimed compound previously existing only in an unseparated mixture was obvious/anticipated; structural identity drives the analysis.
- MPEP § 2144.07 — structural similarity to a prior‑art compound, coupled with an expectation of similar properties, supports obviousness.
- MPEP § 2131.02 / In re Petering — a genus disclosure anticipates species that are "identified" within it; here the specification itself identifies each species by residue range.
Motivation: the applicant's own Background supplies it (an admission usable against the patent): "there is clearly a need for a rapid and a sensitive diagnostic test for the detection of the RV in CNS infection"; "there is also a need for a non-infectious, innocuous vaccine. Such a vaccine could possibly be constructed from synthetic or recombinant peptides of RV proteins." That sentence is a roadmap of the invention's core step.
Why obvious: structure was known (PA‑1–PA‑7), synthesis was routine (PA‑10), and use of short peptides as antigens in immunoassays was routine (PA‑11). Nothing more than predictable application of known techniques.
Ground 2 — The cross‑reactive pan‑meningitis reagent was an articulated, known objective
Combination: PA‑9 (RV mAbs/epitope mapping) + PA‑3/PA‑4/PA‑5/PA‑6 (conserved surface‑protein sequences) + PA‑8 + PA‑13 + PA‑11.
The specification states three separate bacterial "needs": an improved pneumococcal vaccine efficacious in children <2 and adults >65 (cited to U.S. DHHS), a meningococcal vaccine covering serogroup B (for which "no capsular polysaccharide vaccine is available"), and coverage of non‑typeable H. influenzae (for which "no vaccine is efficacious" because anti‑PRP antibody doesn't protect). Each Background section then expressly points to a surface‑exposed protein as the solution — p4/Lipoprotein E, POPM3, pspA, and P60 (the latter with PA‑6 literally teaching that its middle region is exposed on the protein's surface). A PHOSITA would have been motivated, with a reasonable expectation of success, to look for a shared protein epitope enabling a single diagnostic/therapeutic reagent that covers all the major agents — indeed the applicant frames the invention's "improvement" as "screening for bacterial and/or viral meningitis etiologic agents in one test," i.e., the very objective that would have motivated the search.
Why obvious: KSR — identifying conserved regions of known surface proteins from a small, finite set of candidate antigens, then raising mAbs against the immunogen (PA‑8) and screening (PA‑11), yields nothing more than the predictable result of the known method. Also In re O'Farrell, 853 F.2d 894 (Fed. Cir. 1988) ("obvious to try" with a reasonable expectation of success).
Ground 3 — The chemokine linkage is suggested by PA‑7 + PA‑12 + PA‑14
Combination: PA‑7 (MCP‑1/MCP‑3 sequences) + PA‑12 (monocyte carriage into CSF) + PA‑14 (chemokine biology) + PA‑13 (routine homology search).
PA‑12 expressly teaches that bacteria enter the CSF in association with monocytes, and the specification itself notes this "is also analogous to the mechanism employed by some viruses (HIV, Maedi‑Visna‑caprine arthritis encephalitis virus)" — a comparison drawn from the prior art, not from the inventors' data. PA‑14 explains that chemokines are functionally involved in cell chemotaxis and that the family is defined by a conserved four‑cysteine pattern. A PHOSITA with PA‑12+PA‑14 in hand would compare monocyte‑attracting chemokines to the candidate pathogen epitopes by alignment (PA‑13).
Why obvious: A finite set of monocyte‑attracting chemokines was known and sequenced (MCP‑1, MCP‑2, MCP‑3), and the C‑terminal segments QTQTPKT/KTQTPKL were in print (PA‑7). Finding that a pathogen motif aligns with a chemokine C‑terminus is exactly the sort of "predictable solution" KSR treats as obvious, particularly where only five days' effort in a database search separates the claim from the art.
Ground 4 — The diagnostic, kit, method, and therapeutic claims
Combination: any of Grounds 1–3 + PA‑11.
Once the peptide/antibody is possessed (Grounds 1–3), the article‑of‑manufacture, immunoassay, and "analyzing a biological fluid" claims are per se obvious: solid‑phase ELISA, labeled second antibodies, wash/incubate/detect steps, and lyophilized kit components with Tris/phosphate/carbonate buffers, BSA stabilizers and biocides are all disclosed or obvious from PA‑11 and the U.S. patent citations in the specification. Under KSR, combining a newly identified antigen with a known assay format is the paradigm of an obvious combination. Formulation claims likewise reduce to Remington's Pharmaceutical Sciences, 15th ed. (1980), which the specification itself cites.
Ground 5 — The "homolog" genus claims
Standing alone.
Claims (or claim elements) reciting "any amino acid sequence present within a protein that is homologous to members of the MRHAS family," and antibodies defined purely by the ability to block RV‑1 binding or to bind a chemokine "so as to significantly reduce CNS infectivity," are functionally expressed genera. A subsequent computer alignment (PA‑13) against any newly sequenced pathogen satisfies them. Functionally defined claims covering everything that performs a stated function, where the art makes routine the search for that function, are vulnerable under § 103 and § 112(b). Any later‑sequenced genome ipso facto supplies species within the genus, so the claim captures an unbounded, unenabled class.
F. Applicant's best non‑obviousness arguments, and the likely rebuttal
| Applicant argument | Examiner's likely response |
|---|---|
| No art taught that rubella proteins cross‑react with N. meningitidis, S. pneumoniae, H. influenzae, L. monocytogenes and HIV‑1. | The absence of a specific prior report is the definition of the difference the art did not teach — but § 103 asks about predictable results of a known screening method, not about the specific report. Where the art identifies the candidate pathogens, their surface antigens, the clinical overlap (all cause meningitis), the immunochemical toolkit, and the alignment software, the discovery is a routine screening outcome. |
| The claimed motif's homology to MCP‑1/MCP‑3 and the "chemokine mimicry" model of CNS entry is novel. | PA‑12 already taught monocyte‑mediated entry into the CSF; PA‑14 taught what chemokines do; PA‑7 gave the sequences. The only remaining step is alignment. |
| Skepticism: cross‑reactivity might have been carbohydrate/capsular, not protein. | The applicant's own proteinase K data refute the concern — but that finding is confirmatory, not a hurdle any PHOSITA would have regarded as disabling. |
| Claimed peptides are "isolated" and small (7‑mers). | In re Kratz; the "small fragment of known protein" line; and the a/b definitions, which make the claim read on native fragments. |
| Secondary considerations (long‑felt need, commercial success). | The Background establishes the long‑felt need, but the patent supplies no evidence of commercial success, licensing, praise, or unexpected comparative data (no diagnostic sensitivity/specificity figures, no protection data, no neutralization titers). No nexus evidence in the record. |
G. Bottom line
- The strongest § 103 grounds are Grounds 1 and 2: the recited X's are literal subsequences of published protein sequences (PA‑1–PA‑7), combined with routine peptide synthesis (PA‑10) and routine immunoassay practice (PA‑11), with the pan‑meningitis, one-test objective and the synthetic-peptide-vaccine rationale expressly articulated in the patent's own Background. Expect these claims to be difficult to sustain.
- The chemokine-derived claim items (Ground 3) rest on PA‑7 + PA‑12 + PA‑14 + PA‑13 — a routine homology‑search combination under KSR/O'Farrell.
- The specific deposited hybridoma RV‑1 (ATCC HB 11362) is the family's most defensible subject matter, because which single clone emerges from a fusion is not predictable; by contrast, claims to any antibody that binds the epitope — or that blocks RV‑1's binding — are obvious once the epitope is known and antibody technology is routine (PA‑8).
- The diagnostic/kit/method/formulation claims add nothing patentable over PA‑11 and Remington's.
Confidence and limitations (stated explicitly):
- I do not have the patent's front‑page (56) citation list or examiners' search report from the page supplied, so this is a hypothetical analysis, not a reconstruction of an actual Office action.
- I have verbatim text for claim 1 only; the other independent claims were reconstructed from the specification's embodiment language and must be verified against the printed patent.
- There is an unreconciled internal discrepancy (pspA residues 123–129 vs. 423–429; and PPQPPRA vs. PPQPPCA at RV 313–319) between the earlier-generated summary and this family's own Tables. Under your literal-reading rule I have not corrected these; prior‑art mapping for item (xi) depends on which is right.
- Prior‑art dates for Van Damme (JEM, Jan. 1992), Yother (1992), Green (EMBL 1992), and Michiel (Bio/Technology, 1993) should be confirmed against the actual publication months relative to the 1993‑09‑28 priority date; Michiel's 1993 date is the only one I'd verify.
Sources: https://patents.google.com/patent/US5556757/en ; https://patents.google.com/patent/US5510264 ; https://patents.google.com/patent/[US8071102B1](/patent/US8071102B1)/en ; https://patents.google.com/patent/EP2298717B1 ; https://patents.justia.com/patent/[5556757](/patent/5556757) ; https://patents.justia.com/patent/[5510264](/patent/5510264)
Generated 9/27/2026, 5:15:06 PM
Extensions
Patent term adjustments, term extensions, continuations, divisionals, family members, and expiration dates.
Derivative works
Defensive disclosure: derivative variations of each claim designed to render future incremental improvements obvious or non-novel.
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