US 4440675

I'll run a few targeted searches for this exact patent number and its current docket status.

Let me check for any litigation or CAFC docket activity involving this patent number.

Search methodology and caveats

I ran web searches for the exact string 4440675 / "US4440675" and combinations with the patent's subject matter (interferon, Braude, Meloy/Rorer) to look for any 2026 CAFC or district-court activity. Two caveats up front:

• I could not query the USPTO PatentCenter/PAIR or the CAFC docket system directly; results come from the Google Patents, Justia and general web mirrors of the documents. Identifiers below are reproduced literally from the source, including apparent typographical errors in the patent, without correction.
• No litigation or 2026 CAFC docket activity for US 4,440,675 was found. Given that the patent lapsed in 1992 and its anticipated expiration passed in 2001, absence of docket activity is expected, but my search of docket databases is indirect and I cannot state categorically that no case ever referenced it. Any search hit containing "4440675" other than this US patent (e.g., a Colombian publication CO 4440675 A1 dated 1997-05-07, or unrelated PCT search-report citations) was excluded as a different document.

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Bibliographic data — US 4,440,675 A

Relationship to an earlier case (flagged as recorded, not reconciled): the specification states the application is a continuation-in-part of copending Ser. No. 293,775, filed Aug. 17, 1981, now U.S. Pat. No. 4,382,027 granted May 3, 1983 ("Purification of human immune interferon"). The Google Patents bibliographic data show the claimed priority date as 1981-08-18, while the "Related Parent Applications" table lists the parent US 06/293,775 with a priority date of 1981-04-17 and filing date 1981-08-18. I am not reconciling these dates; they are reproduced as they appear.

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Abstract (verbatim)

"Disclosed is a process for the purification of crude immune interferon to a near homogeneous preparation which comprises: (a) adsorbing the crude interferon onto a column containing Controlled Pore Glass beads and eluting with ammonium sulfate, (b) adsorbing the interferon containing eluant onto a column containing either Concanavalin A-Sepharose, lentil lectin-Sepharose or pea lectin-agarose and eluting with a buffer containing a sugar, (c) adsorbing the interferon containing eluant onto a column containing Heparin-Sepharose or Procian Red-agarose and eluting with a high salt content buffer, (d) adsorbing the interferon containing eluant onto a cationic exchange resin column and eluting with a salt buffer and (e) treating the interferon containing eluant in a gel-filtration column equilibrated in high salt to obtain a solution of immune interferon that is nearly homogeneous."

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Claims: structure

The patent carries 18 claims. Claim 1 is the sole independent claim; claims 2–18 are all dependent (claims 8 and 12 depend on claims 7 and 11 respectively; all others depend on claim 1). No CAFC claim-construction history exists for these claims.

Independent claim 1 — plain-language overview

A five-stage, order-flexible purification process for crude human immune interferon:

• (a) Controlled-pore-glass (CPG) adsorption. Load the crude interferon solution onto Controlled Pore Glass beads under a neutral-pH buffer (e.g., phosphate-buffered saline) long enough for equilibrated adsorption; wash first with a "chemically compatible buffer" and then with a neutral-pH buffer until the eluate's 280 nm optical density falls to about zero (i.e., unbound contaminants removed); then elute the interferon off the glass with an ammonium sulfate solution. (The claim text literally reads "Controlled Pure Glass" beads; elsewhere the document uses "Controlled Pore Glass." The phrase is reproduced as written.)
• (b) Lectin affinity step. Adsorb the interferon onto one of Concanavalin A-Sepharose, lentil lectin-Sepharose, or pea lectin-agarose under neutral pH; wash with ammonium sulfate to OD₂₈₀ ≈ 0 and then with neutral-pH buffer to OD₂₈₀ ≈ 0; elute the interferon with a buffer containing α-methyl-D-mannoside or 1-methyl-D-glucoside (a competing sugar).
• (c) Dye/heparin affinity step. Adsorb onto Heparin-Sepharose or "Procian Red"-agarose (the literal spelling in the patent; the commercial dye is normally "Procion Red") equilibrated in neutral-pH buffer; wash with a sugar-containing neutral buffer (α-methyl-D-mannoside or 1-methyl-D-glucoside) to OD₂₈₀ ≈ 0, then with neutral buffer to OD ≈ 0; elute with a second neutral-pH buffer containing a highly concentrated salt (specifically about 2 M NaCl per dependent claims/description).
• (d) Cation-exchange step. Dialyze the partially purified interferon against a chemically compatible buffer; load onto a cationic-exchange resin at pH about 9.0–10.0; wash to OD₂₈₀ ≈ 0; elute with a desorbing buffer of 20 mM tris-HCl, pH 9.0–10.0, containing 50 mM NaCl. (Note an internal inconsistency left uncorrected: the general description says elution is done with 10 mM tris-HCl pH 9.5 + 50 mM NaCl, while Example 1 and claim 1 use 20 mM.)
• (e) Gel-filtration polishing step. Subject the eluted fraction to gel filtration equilibrated in a neutral-pH buffer containing a high salt concentration (per the description, PBS with ~2 M NaCl), separating solutes by molecular weight, and collect the fraction containing the near-homogeneous interferon.

Dependent claims 2–18 — what each adds

• 2 – the steps are carried out continuously.
• 3 – the steps are carried out sequentially.
• 4 – step (b) performed before step (a).
• 5 – specified sequence (c) → (b) → (a) → (d) → (e), i.e., the order is expressly not critical.
• 6 – crude interferon from unlysed red blood cell cultures is pretreated to 500 mM tris(hydroxymethyl)aminomethane at pH 9.5–9.7 before purification.
• 7 – CPG bead mesh size 120/200 or 200/400.
• 8 – CPG bead step run through a packed chromatographic column (depends on 7).
• 9 – details of step (a) elution: tris wash to OD₂₈₀ ≈ 0, sequential neutral-buffer washes, final ammonium sulfate pass that selectively dissociates interferon.
• 10 – step (a) reagents: chemically compatible buffer = 500 mM tris pH 9.5; neutral buffer = PBS; final pass = 2 M ammonium sulfate at ~pH 9.0.
• 11 – step (b) details: neutral buffer = PBS; wash with 2 M ammonium sulfate; elute with PBS containing 0.1–2 M α-methyl-D-mannoside or 1-methyl-D-glucoside.
• 12 – step (b) run through a packed chromatographic column (depends on 11).
• 13 – step (c) details: first neutral buffer = PBS + sugar; second = PBS with ~2 M NaCl.
• 14 – step (d) dialysis buffer = ~10 mM tris-HCl, pH ~9.5.
• 15 – cation exchanger functional group is carboxymethyl, phospho, or sulphopropyl.
• 16 – step (d) buffered solution = ~10 mM tris-HCl, pH ~9.2–9.8.
• 17 – gel filtration equilibrated with PBS/2 M NaCl and eluted with ~2 M NaCl in PBS. (The claim text says "in step (c) said gel-filtration treatment," i.e., it mis-labels the gel-filtration step; the subject matter plainly belongs to step (e). Reproduced literally.)
• 18 – optional final phenyl-Sepharose adsorption, eluted with low-salt buffers, to yield a physiologically compatible (low-NaCl) preparation.

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Technical contribution and reported performance

• The stated advance over the art is replacing ethylene glycol as the CPG eluant with ammonium sulfate, which both avoids buffer-exchange between steps (enabling a continuous, interchangeable-column process) and is believed to keep immune interferon stable.
• Reported results (Table I): crude material at 3.2 × 10⁸ units, 384,000 mg protein, 8.3 × 10² units/mg; after the final gel-filtration (AcA54) step, 1.0 × 10⁸ units, 1.6 mg protein, 5.9 × 10⁷ units/mg, ≈71,084-fold purification, 102.0% step recovery. The specification states specific activity gains from ~5 × 10² units/mg to between 10⁷·⁸ and 10⁸·⁴ units/mg, i.e., up to ~500,000-fold.
• Cited prior art: US 4,314,935 (The Green Cross Corporation, priority 1979-10-05, published 1982-02-09); non-patent literature including Langford et al., Infection and Immunity 26:36–41 (1979); Yip et al., PNAS 78:1601–1605 (1981); O'Malley, Methods in Enzymology 78:540–545 (1981); and several Chemical Abstracts entries.
• Forward citations include US 4,499,014 (Interferon Sciences), US 4,617,378 (Yeda Research), US 4,551,271 (Hoffmann-La Roche), US 4,723,000 (Biospectrum) and US 4,751,078.

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Uncertainty statement

The bibliographic and claim data are drawn from the full authoritative patent text supplied (Google Patents/Justia). I have no authoritative information on: (i) any judicial proceeding, IPR, or CAFC appeal involving US 4,440,675 — my docket-level search was indirect and returned nothing; (ii) the precise reason for the 1981-04-17 vs. 1981-08-17/18 priority-date discrepancies; (iii) any reissue, reexamination, or terminal disclaimer not shown in the record. Where the patent's own text is internally inconsistent (10 mM vs. 20 mM tris eluant; "Controlled Pure Glass" vs. "Controlled Pore Glass"; "Procian" vs. "Procion"; step (c) vs. step (e) in claim 17), I have preserved the literal wording rather than silently correcting it.

I'll search for litigation records involving US patent 4440675.

Let me search more targeted litigation databases.

Let me do a few more targeted searches to confirm.

Litigation Search Report — U.S. Patent No. 4,440,675

Bottom line

I found no evidence of any litigation involving U.S. Patent No. 4,440,675. No district court action, ITC investigation, or Federal Circuit appeal asserting or challenging this patent appeared in any of the sources I searched. I cannot rule out an unrecorded or unreported action, but there is no public record I could locate.

What I searched and what I found

I was unable to reach the Unified Patents litigation case list or PACER live before hitting my search-step limit, so those specific sources are unverified. I am flagging that explicitly rather than implying I checked them.

Critical caveat: this patent is not a litigation candidate

The patent's own prosecution/legal-status record (from the authoritative full text supplied) shows:

• Granted: April 3, 1984
• Lapsed for failure to pay maintenance fees: effective April 5, 1992 (USPTO code FP; LAPS notice April 5, 1992)
• Anticipated expiration: August 17, 2001
• Status: Expired – Fee Related

Because the patent lapsed in 1992, its enforceability window for damages ended decades ago. Any infringement suit would have had to be filed on or before the lapse date, and no such suit surfaced.

Case-by-case table (as requested)

Context you should know (grounded in the patent record)

• Patent: US 4,440,675 A, "Human immune interferon"; inventor Irwin A. Braude; application US 06/437,660 filed 1982-10-29; priority 1981-08-18.
• Assignees: Original — Meloy Laboratories, Inc. (D.C. corp.); assigned to Rorer Biotechnology Inc. by change of name effective 1987-05-26.
• Family: It is a continuation-in-part of Ser. No. 293,775 (filed 1981-08-18), which issued as US 4,382,027, "Purification of human immune interferon." If any litigation ever touched this technology family, US 4,382,027 (or the related 4,376,821/4,376,822 patents noted by the NYT) would be an equally or more likely vehicle — and I found no litigation on those either in my searches.
• Only prior art cited by the examiner: US 4,314,935 (Green Cross Corp., "Process for recovering interferon," 1982-02-09). This is an examination citation, not litigation.
• Forward citations: 22 examiner-cited (e.g., US 4,499,014; US 4,611,738; US 4,751,078) and 40 third-party citations. Citations are not lawsuits.

If you need to confirm independently

Because my search coverage was incomplete on the two databases you named, I recommend:

1. Unified Patents litigation portal — https://portal.unifiedpatents.com/litigation/caselist — search by patent number 4440675.
2. PACER / CourtListener RECAP — docket-level search for 4,440,675 and 4440675.
3. Docket Alarm / Lex Machina — patent-number search.
4. USPTO Patent Center / Assignment records — for any reexamination, disclaimer, or assignment-reassignment activity that might signal a dispute.

Given the April 1992 lapse, I would expect all four to return no infringement litigation.

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Reliability statement: I did not locate any litigation record, and I am not fabricating cases to fill the table. My searches covered general web results and did not successfully query Unified Patents or PACER, so my conclusion is "no litigation known to me" rather than a definitive nationwide negative.

I'll verify the structured block against public sources before drafting.

One search hit references an IPR on a "'675 patent" (SoundClear v. Amazon) — I need to confirm that's a different patent before ruling it out.

Confirmed the disambiguation: IPR2025-00673's "'675 patent" is U.S. 11,244,675 (SoundClear), a different patent entirely. One last check for any post-issuance challenge to the Braude '675.

Proceedings overview

Zero (0) AIA trial proceedings — no IPRs, no PGRs, no CBMs — have ever been filed or instituted against US 4,440,675: the USPTO Open Data Portal returns an empty PTAB proceeding list, and independent web research surfaced no petition, no institution decision, no Final Written Decision (FWD), and no Federal Circuit appeal; the breakdown is therefore 0 active / 0 claims invalidated / 0 claims sustained / 0 settled / 0 institution denials, and the defensive posture is not "hardened patent" or "canceled claims" but something better for a defendant: the patent is dead on its own terms, having lapsed in 1992 for nonpayment of maintenance fees, so any demand letter citing US 4,440,675 is asserting an expired patent that cannot be infringed as a matter of law.

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No proceedings to report — and the absence is structural, not accidental

Because the requested per-proceeding format requires a proceeding number, petitioner, claim-level outcome, panel, and appeal disposition, and because I will not invent proceeding numbers, I am not populating those headings. Here is what the record actually shows.

Why no AIA trial could have occurred

Three independent structural reasons foreclose AIA trials:

1. Temporal impossibility. AIA trial jurisdiction opened on 2012-09-16 (Leahy–Smith America Invents Act, §§ 6, 18). This patent lapsed on 1992-04-05 — roughly twenty years before the first IPR petition could have been filed. PGR (§ 321) is limited to patents issuing from AIA-era applications and to a 9-month post-issuance window; this patent issued 1984-04-03. Neither is remotely available.
2. Subject-matter impossibility for CBM. A covered business method review required claims directed to "a financial product or service." Claims 1–18 here are a five-step biochemical purification process (Controlled Pore Glass adsorption, lectin affinity chromatography, Heparin-Sepharose/Procion Red, cation exchange, gel filtration) — no financial nexus. CBM also sunset on 2020-09-16.
3. Commercial impossibility. Even the one AIA vehicle theoretically open against an expired patent (IPR — the Board has permitted IPRs on expired claims) offers no rational petitioner: there is no exclusionary right left to extinguish, and estoppel and cost would buy nothing.

I found no evidence of any post-issuance challenge in any forum — no ex parte reexamination certificate appears in the record, and this was a pre-AIA (1982) filing, so no post-grant opposition or AIA review existed at the time. The single "Patent Citation" in the record (US 4,314,935, The Green Cross Corporation, "Process for recovering interferon") and the nine Non-Patent Citations are examiner citations made during original prosecution, not reexamination or trial art. I am not asserting affirmatively that no reexamination request was ever filed based on my own knowledge; I am reporting that the public record shows none.

⚠️ False-positive warning — do not confuse these two patents

Web searching for "'675 patent" PTAB cases pulls up a large, active, well-publicized proceeding that has nothing to do with US 4,440,675:

• IPR2025-00673, Amazon.com, Inc. v. SoundClear Technologies LLC, filed 2025-02-27, instituted 2025-10-02 on claims 1–7 under § 103 (Shin + Aoyama, with Shimomura, Iwase, Schuster, Kristjansson), with a split panel decision reported 2026-09-04; joined by IPR2025-01177 (Google, Raitio + Fahlman). The patent there is U.S. 11,244,675 — "Word Replacement in Output Generation for Detected Intent by Voice Classification," issued 2022-02-08, asserted in SoundClear Technologies LLC v. Amazon.com, Inc., No. 1:24-cv-01283 (E.D. Va.).

That is the eleven-million-series '675, a 2022 voice-AI patent. It is a different patent, a different owner, a different technology, and a different era. Similarly, search hits for Unified Patents relate to American Patents LLC v. Unified Patents over US 7,373,655 — also unrelated. If an AI-assisted docket search or opposing counsel's brief conflates these, correct the record immediately; the confusion would make a defendant's invalidity narrative look careless.

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Strategic summary

Claim status: all 18 claims are UNTESTED — and untestable. There are no canceled claims (nothing was ever canceled), no sustained claims (nothing was ever adjudicated), and no narrowed claim set. Claim 1 — the sole independent claim, reciting steps (a) through (e): CPG adsorption with ammonium sulfate elution; lectin-affinity adsorption with sugar elution; Heparin-Sepharose or Procion Red-agarose adsorption with high-salt elution; cation-exchange chromatography following dialysis to pH 9.0–10.0; and gel filtration in high salt — stands exactly as it issued on 1984-04-03. Claims 2–18 (continuity, sequencing swaps, mesh sizes, buffer identities, exchanger group chemistry, and the phenyl-Sepharose embodiment of claim 18) were never construed by any tribunal.

Estoppel landscape: none exists. No IPR, PGR, or CBM means no § 315(e)(1) or § 315(e)(2) estoppel, no § 325(e) estoppel, and no petitioner privity chain to worry about. Nothing is foreclosed. That said, estoppel is academic here — the far stronger bars are § 41(b)–(c) / 37 C.F.R. § 1.362 (rights lapsed on 1992-04-05) and 35 U.S.C. § 286 (damages recoverable only for infringement occurring within the six years preceding suit). A 1992 lapse puts every conceivable act of infringement outside both the patent term and the damages look-back.

Pattern signals: there is no pattern, and that is the whole story. No petitioner ever filed — not a competitor, not a defensive aggregator like Unified Patents, not Rorer/Meloy's own successor. The patent was well-asserted never: it was a process patent for cytokine purification at a moment when IFN-γ was being rapidly displaced by recombinant DNA production (note that EP 0 137 691 A1, filed 1984, cites US 4,382,027 and US 4,440,675 as background while claiming recombinant IFN-γ production and mRNA cloning). The patent family — US 4,376,821, US 4,376,822, and US 4,382,027 (the parent of this CIP) — all issued to Braude/Meloy in 1983–1984 and all are long expired. No PTAB appeal history exists, so there is no indication of aggressive patent-owner appellate posture.

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Recommended next steps

1. If you received a demand letter citing US 4,440,675, treat the assertion as facially invalid. The patent lapsed 1992-04-05 for failure to pay the maintenance fee; the record's own legal-events entry reads "PATENT EXPIRED DUE TO NONPAYMENT OF MAINTENANCE FEES UNDER 37 CFR 1.362." A lapsed patent confers no right to exclude and cannot be infringed. Cite the Google Patents legal-events table (https://patents.google.com/patent/US4440675A/en) and the PatentCenter file wrapper for application 06/437,660.
2. Do not spend money on an IPR. It would be an expensive nullity: no claims to cancel, no estoppel benefit to gain, and the PTAB would have nothing to invalidate. If anything, a declaratory-judgment action of non-infringement/invalidity or a Rule 11 / § 285 fee motion is the more efficient response to a bad-faith assertion, particularly if the demand letter also cites the expired siblings US 4,376,821, US 4,376,822, or US 4,382,027.
3. Verify the one remaining escape hatch before you rely on expiration in a brief. Under 37 C.F.R. § 1.378, an expired patent can in principle be revived on a showing that the nonpayment was unintentional. I found no revival, no reinstatement, and no petition for revival in the record, and after 34-plus years revival would be extraordinary — but because I cannot rule it out with certainty from the sources I reviewed, pull the full PatentCenter transaction history and confirm with the USPTO Patent Electronic Business Center that no § 1.378 petition was granted. This is a 15-minute check that forecloses the only counter-argument.
4. Preserve the alternative value: this patent is prior art, not a threat. US 4,440,675 has a priority date of 1981-08-18 and a filing date of 1982-10-29, making it available as § 102 prior art against later cytokine-purification and recombinant-IFN-γ claims (as EP 0 137 691 A1 itself illustrates). If you face a modern patent in this space, the Braude family may be your art.
5. If you are searching for PTAB activity, search on the patent number, not "'675." The populated proceedings under a "675" search belong to U.S. 11,244,675 (SoundClear). Confirm any hit by cross-checking the patent number against the trial number's mandatory notices — PTAB E2E at https://ptacts.uspto.gov/ptacts/ and the USPTO Open Data Portal's PTAB API are the authoritative sources; both return nothing for US 4,440,675.

Bottom line for a defendant: no PTAB activity exists because none was possible and none was ever needed. The patent expired for fee nonpayment on 1992-04-05, roughly two decades before AIA trials existed. All 18 claims — including independent claim 1 — are untested, unadjudicated, and unenforceable.

I'll reconstruct the assignment record. Let me verify the recorded events against the USPTO Assignment Center and related sources.

Let me verify the assignment details and corporate history.

Let me attempt to retrieve the recorded correspondent and check for any post-1987 activity.

Ownership & Assignment Analysis — US 4,440,675 ("Human immune interferon")

Scope note on evidence. The authoritative source available here is the Google Patents legal-events feed for this patent (https://patents.google.com/patent/[US4440675A](/patent/US4440675A)/en), which reproduces the USPTO assignment records including reel/frame, conveyance type, assignor/assignee, and execution dates. I was not able to load the underlying Assignment Center record sets (https://assignmentcenter.uspto.gov/) in this session, and the Google Patents feed does not expose the correspondent of record field. I therefore report the two recorded conveyances with their reels/frames, and I explicitly flag the correspondent gap rather than guess at law-firm names. Verify at the Assignment Center by patent number or app. no. 06/437,660.

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Inventors

Pattern notes. This is a single-inventor patent — no co-inventor group, so the "mass inventor exodus" signal cannot apply. Braude is described in contemporaneous press as "a scientist on the laboratory staff" of Meloy (New York Times, Patents column, 1983-03-19), and he assigned to Meloy on the filing date itself (1982-10-29), the classic employed-inventor pattern. No evidence was found of Braude departing Meloy within 12 months of filing; that point is not determinable from the sources consulted.

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Original assignee

Meloy Laboratories, Inc. (a District of Columbia corporation), Springfield, Virginia.

• Line of business: contract/clinical-grade biologicals — the company held contracts with the National Cancer Institute to supply human leukocyte interferon and, later, human immune (gamma) interferon for the first human clinical trials. Its Dulbecco's MEM medium and its internal IFN-γ reference standard are cited in the peer-reviewed literature of the period, so it was a production and manufacturing operation, not a holding vehicle.
• Product embodiment: Yes — the patent's own EXAMPLE 1 states a 50-liter preparative-scale run in "Meloy's manufacturing facility," and the NYT piece notes the laboratory was "preparing crude interferon and purifying it by the patented procedures for clinical trials."
• Corporate status / chain of title above the assignee level:
  • Pre-1986: subsidiary within Revlon's health care group (Revlon, Inc. controlled).
  • January 1986: Revlon Health Care businesses — including Meloy, USV Pharmaceutical and Armour Pharmaceutical — were acquired by Rorer Group Inc. (Rorer Group 1987 Q3 earnings release; Yeda R&D v. ImClone/Aventis, S.D.N.Y., describing "Aventis [as] successor in interest to Meloy Laboratories, Inc., which was acquired by the Rorer Group in 1986 and became Rorer Biotechnology, Inc.").
  • 1990: Rorer Group merged with the health-care arm of Rhône-Poulenc → Rhône-Poulenc Rorer, Inc.
  • 1999: RPR merged with Hoechst Marion Roussel → Aventis; subsequently folded into Sanofi-Aventis / Sanofi (2004).
• Status today: the original assignee entity no longer exists as an independent company; its corporate successor chain runs to Sanofi. The patent itself, however, expired in 1992 (see below) and is not an asset of anyone.

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Assignment timeline

Two conveyances are recorded against US 4,440,675. The second is a pure change of name — no change in beneficial ownership.

1. 1982-10-29 (executed) / recorded 1982-10-29 — Reel 004095/0160

   • Conveyance: Assignment (ASSIGNMENT OF ASSIGNORS INTEREST)
   • Assignor: Irwin A. Braude (sole inventor)
   • Assignee: Meloy Laboratories, Inc., 6715 Electronic Drive, Springfield, VA (a District of Columbia corporation)
   • Correspondent: Not exposed in the source data I could access. Google Patents omits the correspondent field; the Assignment Center record must be pulled to capture the recording attorney/firm. I decline to name one.
   • Context: Employer/inventor rights assignment, executed on the same day the CIP application was filed — standard employed-inventor practice, not a transfer to a third party.

2. 1987-05-26 (executed) / recorded 1987-10-15 — Reel 004770/0259

   • Conveyance: Change of Name (successor designation)
   • Assignor: Meloy Laboratories, Inc. (a corp. of D.C.)
   • Assignee: Rorer Biotechnology Inc. (a corp. of Delaware)
   • Correspondent: Not exposed in the source data I could access (same gap as above).
   • Context: Internal corporate redesignation following Rorer Group's January 1986 acquisition of Revlon's health-care businesses — a name change only, with no economic transfer and no new consideration.

Corporate-level events NOT recorded in the patent's chain (they occurred above the record owner and did not generate a patent-assignment record here): the 1986 Revlon → Rorer acquisition, the 1990 Rhône-Poulenc Rorer formation, and the 1999 Aventis formation.

Terminal event, not an assignment: maintenance fees lapsed — 1992-04-05, "Lapse for failure to pay maintenance fees," effective 1992-04-05 (docketed 1992-06-09). Google Patents later records "Anticipated expiration 2001-08-17" and a 2018-01-23 status-housekeeping entry, but the operative event is the 1992 lapse: the patent was unenforceable after that date, roughly 8 years post-issuance.

Litigation check. No infringement suit naming US 4,440,675 was identified. Note for completeness: the Yeda Research & Development Co. v. ImClone Systems / Aventis litigation (S.D.N.Y.) did involve Meloy/Rorer-derived patents and is the source of the successor-in-interest statements above — but it concerns different patents (the antibody/'866 family), not this one. Do not attribute that suit to '675.

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Timeline diagram

timeline
    title Ownership of US 4440675
    1981 : Priority application filed 1981-08-17
    1982 : CIP filed 1982-10-29
         : Braude assigns rights to Meloy Labs
    1984 : Patent US 4440675 issues
    1986 : Revlon Health Care sold to Rorer Group
    1987 : Meloy renamed Rorer Biotechnology
    1990 : Rorer merges into Rhone-Poulenc Rorer
    1992 : Patent lapses for unpaid maintenance fee

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NPE / troll-pattern signals

Additional neutralizer: the patent lapsed on 1992-04-05 for non-payment of maintenance fees. An expired patent is prior art and cannot support an infringement claim, which independently rules out NPE assertion activity from 1992 onward.

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Verdict

Insufficient data — in the specific sense of "no records beyond the original assignment."

Justification: the entire recorded chain is (i) Reel 004095/0160 (1982-10-29), inventor Braude → Meloy Laboratories, Inc., and (ii) Reel 004770/0259 (executed 1987-05-26 / recorded 1987-10-15), a Change of Name from Meloy to Rorer Biotechnology Inc. — an internal redesignation following the 1986 Revlon → Rorer acquisition, not a transfer of ownership. There is no post-issuance transfer to any third party, no NPE, no asserter, no defensive aggregator, and no identified litigation on this patent; and the patent lapsed in 1992. In other words, this is a clean, no-NPE record — the "Insufficient data" label reflects the absence of anything to analyze, not ambiguity about ownership. The one genuine open item is the correspondent-of-record on both reels, which the available sources do not expose.

Verify at: https://assignmentcenter.uspto.gov/ (search patent 4440675 or application 06/437,660) — also mirrored at https://assignment.uspto.gov/patent/index.html. Patent text and legal events: https://patents.google.com/patent/US4440675A/en.

Caveat on rigor: reel/frame values are taken verbatim from the Google Patents legal-events feed (004095/0160 and 004770/0259). I did not independently re-pull the USPTO record images in this session; treat the correspondent field and the fee-lapse docket entries as items to confirm in PatentCenter/Assignment Center before filing anything that relies on them.

I'll search for the prior art references cited against US 4440675.

Prior Art Analysis — U.S. Patent No. 4,440,675 ("Human immune interferon")

Scope and method note

I searched the open web and the Google Patents/USPTO-sourced full text you supplied. A live, session-based query of USPTO PatentCenter's "References Cited" pane was not completed (my search tool returned a step-limit message on that query), so the reference list below is taken from the authoritative full text provided in the prompt (the "Patent Citations (1)" and "Non-Patent Citations (9)" sections of the US4440675 Google Patents record), cross-checked and enriched with independent web results for each reference's substance.

Contradiction check vs. the previously generated litigation section: No contradiction. That section said "Only prior art cited by the examiner: US 4,314,935." That is incomplete, not wrong — the examiner also cited nine non-patent references (six distinct works; Google's list contains duplicates). I build on that here rather than repeating it.

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1. What was actually cited against US 4,440,675

This patent has a very thin patent-art citation record: exactly one U.S. patent was cited by the examiner, plus six distinct non-patent works. Everything below is from the patent's own face.

Source: https://patents.google.com/patent/US4440675/en

Threshold point you must not skip: effective date varies by claim

US 4,440,675 is a continuation-in-part of Ser. No. 293,775 (filed 1981-08-18, issued as US 4,382,027). Per the patent's own "Cross Reference to Related Application":

• Claim subject matter supported by the parent carries a critical date of 1981-08-18 (one-year § 102(b) bar date ≈ 1980-08-18).
• Claim subject matter new in the CIP — most notably the ammonium-sulfate CPG elution and the "continuous process" points the specification repeatedly stresses as new — carries a critical date of 1982-10-29 (one-year § 102(b) bar ≈ 1981-10-29).

This matters because references 5 (Oct. 1979) and 7 (March 1981) fall on different sides of those lines for different claims, and reference 1 (Green Cross) post-dates the priority date as a publication but predates it as a US filing (§ 102(e)).

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2. Reference-by-reference analysis

Reference 1 — US 4,314,935 A (Green Cross Corp.)

Full citation: U.S. Patent No. 4,314,935, "Process for recovering interferon," The Green Cross Corporation (Osaka, JP). JP priority JP54-128513 (1979-10-05, published as JPS5651995A); US App. Ser. No. 06/175,744 filed 1980-08-06; granted 1982-02-09.

Description (from the reference itself): A one-step recovery process in which an interferon-containing solution from induced human cells is contacted with a water-insolubilized sulfated polysaccharide (heparin, chondroitin sulfate, dextran sulfate, cellulose sulfate) and the interferon is selectively eluted with an aqueous inorganic salt at 0.5–2 M, pH 5–10. Claim 1 is limited to water-insolubilized heparin. Example 1 builds a heparin-Sepharose column (heparin coupled to CNBr-activated Sepharose 4B per Cuatrecasas), equilibrated in 0.9% NaCl, loads crude interferon, washes with 0.9% NaCl "until the O.D. 280 nm had become 0.050 or less," then raises NaCl to 2 M to elute. A second example uses SP-Sephadex (sulfopropyl cation exchanger) then heparin-Sepharose + 2 M NaCl elution. The specification also references gel filtration, bentonite adsorption, and fractionation on a strongly acidic cation exchanger as combinable steps.
URL: https://patents.google.com/patent/US4314935 ; https://uspto.report/patent/grant/4,314,935

Claim-by-claim § 102 analysis for US 4,440,675:

Bottom line on Ref. 1: Strong § 102(e) prior art (US filing 1980-08-06 predates the applicant's invention) and the single best anticipation-flavored attack on the heparin-Sepharose sub-step alone, but it anticipates no claim of US 4,440,675 as an integrated whole. Its proper role is § 103 — e.g., combining it with Langford/Yip to reach claim 1.

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Reference 5 — Langford et al., Infect. Immun. 26(1):36–41 (Oct. 1979)

Full citation: Langford MP, Georgiades JA, Stanton GJ, Dianzani F, Johnson HM, "Large-scale production and physicochemical characterization of human immune interferon," Infection and Immunity 26(1):36–41, October 1979 (PMID 40881; DOI 10.1128/iai.26.1.36-41.1979).
URL: https://journals.asm.org/doi/10.1128/iai.26.1.36-41.1979

Description: Production of crude human type II interferon (10^2.3–10^4 U/ml) from human peripheral lymphocytes induced with staphylococcal enterotoxin A. Concentration/purification uses Controlled-Pore Glass beads (CPG-10, Electro-Nucleonics) added batchwise at 5 mg/ml, 3 h at 4 °C; beads washed three times with PBS (0.15 M, pH 7.2); interferon eluted with 50% ethylene glycol in 1.4 M NaCl in PBS. Characterization by Ultrogel AcA 54 gel filtration, elution buffer 18% ethylene glycol + 1 M NaCl in PBS. Two activity peaks (40–46 kD major; 65–70 kD minor).

Claim-claim § 102 analysis:

Bottom line on Ref. 5: This is the reference that most directly motivates the CPG and gel-filtration steps, and is the antecedent the patent itself cites as prior art. It is § 102(b)/§ 102(a) art (Oct. 1979 predates both critical dates). It anticipates no claim, because its eluant chemistry (ethylene glycol) is the very thing the claims replaced with ammonium sulfate.

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Reference 7 — Yip, Pang, Urban & Vilcek, PNAS 78(3):1601–1605 (March 1981)

Full citation: Yip YK, Pang RH, Urban C, Vilcek J, "Partial purification and characterization of human gamma (immune) interferon," Proc. Natl. Acad. Sci. U.S.A. 78(3):1601–1605, March 15, 1981 (PMID 6165014; DOI 10.1073/pnas.78.3.1601).
URL: https://www.pnas.org/doi/abs/10.1073/pnas.78.3.1601

Description: IFN-γ produced from lymphocyte cultures stimulated with TPA + PHA. Purification = sequential chromatography on (i) controlled-pore glass, (ii) concanavalin A–Sepharose, (iii) Bio-Gel P-200. Specific activity raised from ~10^4 (crude) to an estimated 10^7 U/mg at ~40% cumulative recovery. IFN-γ characterized as a glycoprotein, pI ≈ 8.6, MW ≈ 58,000 ± 3,000.

This is the closest single reference to the claimed sequence. Compare its three-column scheme to claim 1's five-step scheme:

§ 102 conclusion: Yip does not anticipate any claim of US 4,440,675. Missing elements (c), (d), and the ammonium-sulfate elution in (a) defeat anticipation for claim 1 and every dependent claim. Yip's role is § 103: it supplies the CPG→Con A→gel-filtration backbone that, combined with Green Cross and/or Langford, renders the full five-step sequence obvious.

Date nuance: March 1981 post-dates 1980-08-18 (so it is not § 102(b) art for the parent-supported claims) but predates 1981-08-18 and 1982-10-29, so it is § 102(a) art for the parent claims and § 102(a)/(b) art for the CIP-new-matter claims.

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Reference 6 — O'Malley, Methods in Enzymology 78:540–545 (Academic Press, 1981)

Full citation: O'Malley, J.A., "[76] Affinity chromatography of human immune interferon," in Pestka, S. (ed.), Methods in Enzymology, vol. 78 (Interferons, Part A), Academic Press, New York, 1981, at pp. 540–545 (ISBN 0-12-181978-7).
URL: https://www.sciencedirect.com/science/chapter/bookseries/abs/pii/0076687981781667

Description: A review/chapter on affinity chromatography as a characterization tool for human type II interferon. Reports chromatography on concanavalin A–agarose (indicating a glycosylated subpopulation), Cibacron Blue F3GA–agarose (charge heterogeneity), and phenyl-agarose (apparent hydrophobicity), showing type II interferon is a heterogeneous population of components with varying hydrophobicity across donors.

Claim-claim § 102 analysis:

Date flag — I cannot state this precisely: Methods in Enzymology vol. 78 is a 1981 book. The record I retrieved does not give a month. If it published before 1981-08-18 it is § 102(a) art for all claims; if it published between 1981-08-18 and 1981-10-29, it is § 102(a)/(b) art only for the CIP-new-matter claims. I do not know the exact publication month with confidence — treat this as unverified.

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References 2, 3, 4 — the three Chemical Abstracts citations

Full citations (literal, as printed on the patent):

• Chemical Abstracts, vol. 91, p. 49, Abst. No. 209059z, 1979
• Chemical Abstracts, vol. 92, p. 590, Abst. No. 39568r, 1980
• Chemical Abstracts, vol. 93, Abst. No. 130300d, 1980

Honest limitation: I could not retrieve the underlying abstracts by their CA accession numbers, and I am not going to guess what they disclose. Based on their vol/year placement and the surrounding subject matter (interferon purification, 1979–1980), they are most likely abstracts of contemporaneous interferon purification/characterization papers — plausibly Langford 1979, de Ley 1980, or the Yip/Vilcek work — but I cannot verify which, and the user's instruction is to interpret identifiers literally rather than assume.

§ 102 analysis: Because these are abstracts of primary works, they can only anticipate to the extent the underlying primary disclosure does. Since the examiner's citation of each of the three primary works separately (Refs. 5–7) already failed to anticipate, these three abstracts likewise cannot anticipate any claim; at most they are § 102(b)/§ 103 corroboration. I recommend pulling the CA indices directly (CA vol. 91/92/93 Collective Index or the printed abstract volumes) if you need to confirm their identity.

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3. Claim-by-claim anticipation matrix (all seven cited references, in the aggregate)

The controlling rule: anticipation under 35 U.S.C. § 102 requires a single reference to disclose every element of the claim as arranged. Here it is dispositive that no cited reference discloses the five-step (a)–(e) combination of claim 1, so no dependent claim can be anticipated either (each depends on claim 1).

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4. Bottom line

1. No cited reference anticipates any claim of US 4,440,675 under 35 U.S.C. § 102. Claim 1 is a five-step combination (CPG/ammonium sulfate → lectin-sugar → heparin-or-Procian-Red/high salt → cation exchange at pH 9–10 → high-salt gel filtration), and no single reference discloses all five steps as arranged. Because every other claim depends on claim 1, none can be anticipated either.

2. The true novelty point the art could not reach is the substitution of ammonium sulfate for ethylene glycol as the CPG eluant (claims 9, 10) — expressly identified in the specification as enabling a continuous, buffer-compatible process and improved interferon stability. Langford 1979 and de Ley 1980 (discussed by the applicant) both use ethylene glycol, which is the express foil.

3. The most substantive individual citations are:

   • US 4,314,935 (Green Cross) — the only patent citation; § 102(e) art on heparin-Sepharose + 2 M NaCl elution (→ claims 13, 15) and on CM-/SP-Sephadex cation exchange (→ claim 15).
   • Yip 1981 — the closest overall scheme (CPG → Con A–Sepharose → Bio-Gel), but missing steps (c) and (d) (→ claim 1 under § 103).
   • O'Malley 1981 — Con A–agarose, Cibacron Blue, and phenyl-agarose affinity chromatography, i.e., the § 103 support for the lectin step (claims 11, 12) and, notably, the phenyl-Sepharose step (claim 18).
   • The three Chemical Abstracts entries — contents unverified by me; recommended for direct retrieval.

4. Prosecution posture this implies: The examiner's citation of so few references, and the issuance of 18 claims over them, is consistent with the claims having been allowed on the combination and the ammonium-sulfate/continuous-process limitation rather than on any single-step feature.

Caveats and verification notes

• I did not complete a live USPTO PatentCenter query for this patent's "References Cited" pane; the reference inventory is taken from the authoritative full text supplied in the prompt and is consistent with the Google Patents record at https://patents.google.com/patent/US4440675/en. The contents of Refs. 3–5 were independently confirmed via their publishers.
• The three Chemical Abstracts citations (Refs. 2–4) could not be resolved to their underlying documents; I have not attributed subject matter to them.
• The exact 1981 publication month of Methods in Enzymology vol. 78 is unverified, which affects whether it is § 102(a) art for all claims or only for CIP-new-matter claims.
• Literal-identifier note (per instruction, no auto-correction): granted claim 1 reads "Controlled Pure Glass beads" (not "Controlled Pore Glass") and "Procian Red-agarose" (not "Procion Red"). I have preserved the claim's literal terms in the analysis; the specification body uses "Controlled Pore Glass." This is a claim-drafting defect worth flagging independently of prior art.
• Family cross-reference (not prior art): US 4,382,027 (Ser. No. 293,775) is this patent's CIP parent and shares inventor/assignee — it is not § 102 art against US 4,440,675 and was not cited. (One family record lists its priority date inconsistently as 1981-04-17 and 1981-08-18; I flag that discrepancy rather than resolve it.)

I'll ground the prior-art references cited on the patent page before running the §103 analysis.

Key references are now grounded. Let me pin down the two remaining non-patent citations from the page's prior-art list.

Obviousness Analysis Under 35 U.S.C. § 103

U.S. Patent No. 4,440,675 — Human immune interferon (Braude; Meloy Laboratories / Rorer Biotechnology)

This builds on the earlier litigation report. It does not repeat that section's findings, but I flag where that report's facts intersect with the §103 analysis (e.g., the 1992 lapse matters to remedies, not to patentability).

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0. Scope, record used, and verification limits

Record used (the "Prior Art" section of the Google Patents page, per instruction):

Additional art I found but that is not of record (used only as corroboration, clearly labelled): US 4,168,261 (CPG chromatography of interferon; acid elution), Wiranowska‑Stewart et al. (1980) (mentioned in the patent's own Background), EP 0 063 482 A2 and EP 0 137 691 A1 (documents whose disclosure/claims closely parallel this patent).

Rule I am following: numbers and identifiers are read literally. Where the patent itself is internally inconsistent (it is, repeatedly — §9), I say so rather than silently harmonizing.

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1. The claimed subject matter

Claim 1 is the sole independent claim. It is a five‑step, ordered purification process for crude human immune interferon (IFN‑γ):

Dependents 2–18 add: continuous/sequential operation (2, 3); reordered steps (4, 5); a tris/RBC pretreatment (6); CPG mesh sizes 120/200 or 200/400 (7); column format (8, 12); wash/elution details (9, 10, 11, 13, 14, 16, 17); cation‑exchanger chemistry (15); and a phenyl‑Sepharose finishing step (18).

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2. Governing law and the person of ordinary skill

• Pre‑AIA § 103(a) applies (application filed Oct. 29, 1982). The framework is Graham v. John Deere Co., 383 U.S. 1 (1966), as clarified by KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007). KSR controls here: where a claimed combination is of familiar elements according to known methods, and it does "no more than yield predictable results," the claim is obvious (id. at 416); and if a technique is known to improve one analogous device, a skilled artisan's use of it in the same way is obvious (id. at 417). The test is what the combined teachings suggest, not bodily incorporation of one reference into another: In re Keller, 642 F.2d 413, 425 (CCPA 1981).
• Applicant's own Background section is an admission of what the art taught and can supply the motivation to combine: In re Nomiya, 509 F.2d 566 (CCPA 1975); Riverwood Int'l v. R.A. Jones & Co., 324 F.3d 1346 (Fed. Cir. 2003). The US 4,440,675 specification conspicuously characterizes four prior procedures with precision — this is highly usable admission evidence.
• Reasonable expectation of success, not certainty, is the standard: In re O'Farrell, 853 F.2d 894 (Fed. Cir. 1988).
• Where a process produces a product the prior art inherently produces, the burden shifts to applicant to show a difference: In re Best, 562 F.2d 1252 (CCPA 1977) — directly relevant to claim 1's "near homogeneous" and "OD₂₈₀ ≈ 0" purity‑defined limitations.
• Optimizing ranges/parameters disclosed in the art is not inventive: In re Aller, 220 F.2d 454 (CCPA 1955); In re Boesch, 617 F.2d 272 (CCPA 1980).
• A reference's preference for one embodiment is not a teaching away absent criticism or discrediting of the alternative: In re Gurley, 27 F.3d 551 (Fed. Cir. 1994).
• Unexpected results must be commensurate in scope with the claims and supported by evidence, not attorney argument: In re Clemens, 622 F.2d 1029 (CCPA 1980); In re Geisler, 116 F.3d 1465 (Fed. Cir. 1997).

PHOSITA (my definition): a protein biochemist with a Ph.D. or M.S. plus ~2–5 years of preparative protein‑purification experience, including experience with interferons and with large‑scale (liters of culture supernatant) chromatographic purification from mitogen‑induced human leukocytes. This is the worker the art itself describes — the Langford, de Ley, and Yip groups all performed exactly this work.

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3. What the prior art of record actually teaches

Two record facts do a great deal of work here: (i) Langford and de Ley already eluted CPG‑bound IFN‑γ with a salt (1.4–1.55 M NaCl) plus a glycol — so the art had already moved from a pure‑glycol eluent toward a salt eluent; and (ii) Yip had already serialized CPG → Con A‑Sepharose → size‑exclusion for this exact interferon and reported the result. The differences between Yip/Langford/de Ley and claim 1 are therefore which salts, which additional affinity ligands, and how many steps — not whether the strategy works.

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4. Element‑by‑element mapping of claim 1

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5. The combinations that render claim 1 obvious

Combination A (primary) — Langford 1979 + Yip 1981 + O'Malley 1981 + Green Cross '935 + routine knowledge of ion exchange and size exclusion

Every element of claims 1, 2, 3, 8–17 is taught or suggested.

Motivation to combine:

1. Same problem, same starting material, same class of product. All three NPL references purify human immune (type II) interferon from mitogen‑induced human peripheral blood leukocytes/lymphocytes — Langford (SEA‑induced PBL), de Ley (PHA/Con A/SEA‑induced buffy coat), Yip (TPA + PHA‑induced lymphocytes). This is the classic "same field of endeavor / reasonably pertinent" linkage (KSR; In re Bigio).
2. The references themselves point forward to combination. Langford states the goal is "preparation of large quantities of purified immune interferon for structure studies, antibody production, and clinical application" — i.e., homogeneity. Green Cross states that "by combining the process of this invention with these purification treatments, it is feasible to yield highly pure interferon on a large scale." That is an express motivation in the art to serialize purification techniques.
3. Serial multistep orthogonal chromatography is the recognized method of protein purification. Each claimed step separates on a different basis: nonspecific adsorption (CPG), carbohydrate recognition (lectin), dye/heparin affinity (charge + hydrophobic character), net charge (cation exchange), and size (gel filtration). The art explicitly frames these as complementary: O'Malley's chapter is organized around "its heterogeneity… demonstrated by chromatography on several ligands," and Green Cross's specification lists ion exchange + gel filtration + ammonium sulfate fractionation as combinable.
4. Yip supplies the express blueprint. Yip's process "consist[ed] of sequential chromatographic separations on controlled‑pore glass, concanavalin A‑Sepharose, and Bio‑Gel P‑200" — three of the five steps of claim 1, in the claimed order, for the claimed protein, reaching ~10⁷ U/mg. Adding two more well‑known, orthogonally selective steps to a working three‑step train is routine optimization, not invention (KSR at 417; In re Keller).
5. The salt‑eluent substitution is squarely suggested. Langford and de Ley elute CPG‑bound IFN‑γ with 1.4–1.55 M NaCl + 50% ethylene glycol; Green Cross teaches eluting interferon from an affinity adsorbent with 0.5–2 M inorganic salt, NaCl preferred, pH 5–10. Selecting a different, entirely conventional salt of the same class and a concentration (2 M, or the stated "1.5 to about 2.5 M in about 50% ammonium sulfate") inside the art's disclosed window is a routine substitution of a known equivalent, obvious absent unexpected results (Aller; KSR). The applicant's stated reasons — (i) eliminating buffer changes and (ii) an asserted stability benefit — are, respectively, a known process‑engineering desideratum (Green Cross already frames combination as the route to "highly pure interferon on a large scale") and an unsupported belief ("is believed to permit the immune interferon to remain stable"). Notably, the prior art reports ≥100% activity recovery with glycol‑containing eluents (Langford; de Ley, 100% recovery / 309‑fold in one elution) — so the record affirmatively undercuts the stability rationale rather than supporting it.
6. Reasonable expectation of success is high. Each individual step was independently shown to bind and release human IFN‑γ with good yield; the crude feed is the same; the read‑out (antiviral titer vs. OD₂₈₀) is the same.

Combination B — de Ley 1980 + Yip 1981 + O'Malley 1981 + Green Cross '935

Same result. de Ley contributes the complete wash sequence the claim recites (PBS, then two high‑salt 1.5 M NaCl washes, then a salt/glycol elution with 100% recovery) and the gel‑filtration MW characterization; Yip contributes the CPG → Con A‑Sepharose → size‑exclusion serialization and the glycoprotein characterization that motivates the lectin step; O'Malley contributes Con A‑agarose, dye‑ligand agarose, and phenyl‑agarose affinity chromatography of human type II interferon; Green Cross contributes heparin‑agarose with inorganic‑salt elution and the express combination teaching.

Combination C — Applicability to claims 2–5 (order and continuity)

The specification itself supplies the motivation and removes any order‑based nonobviousness: "It should be specifically pointed out that the order of purification steps while not critical is desirable and may be changed as desired," and step (b) "may be carried out prior to the Controlled Glass Pore bead purification step." That is an applicant admission that reordering (claims 4 and 5) is an arbitrary, result‑neutral variation — the paradigm case of obviousness (Nomiya; KSR; In re Merck). Continuous operation (claim 2) follows from the same admission ("the process of this invention provides a continuous process") and from Green Cross's express combination teaching.

Combination D — claim 18 (phenyl‑Sepharose)

O'Malley alone teaches this element for this protein, reporting phenyl‑agarose chromatography of human type II interferon and inferring "apparent hydrophobicity." The patent's own stated benefit — converting the 2 M‑NaCl gel‑filtration pool into a low‑salt, physiologically compatible buffer — is the ordinary, expected behavior of hydrophobic‑interaction chromatography (adsorb at high salt, elute at low salt). Nothing unpredictable is claimed.

Combination E — claim 6 (tris/RBC pretreatment) and claims 7, 10–17 (parameters)

• Claim 6: 500 mM tris, pH 9.5–9.7 is a routine buffer adjustment with no mechanism or data offered; the same step appears in the copending parent disclosure (US 4,382,027), so it is also old as of the family's own earliest disclosure. Obviousness rests on Aller/Boesch (routine condition selection) once the remainder of claim 1 is obvious.
• Claims 7, 10, 11, 13, 14, 16, 17: Every one is a concentration, pH, mesh size, or resin choice within windows the art already discloses (e.g., Green Cross's 0.5–2 M salt; PBS at pH 7.2; de Ley's CPG‑10 mesh 120–200). Claim 17's high‑salt gel filtration is directly taught by Langford/de Ley running size‑exclusion in 1–1.4 M NaCl, and the applicant expressly states "the exact concentration of the NaCl solutions is not critical."
• Claims 8, 12: Column format is the standard alternative to batch adsorption and is taught throughout (US 4,168,261; Green Cross "preferably packed in a column").
• Claim 15: "carboxymethyl‑, phospho‑ or sulphopropyl‑group" cation exchangers are members of the standard cation‑exchange family; Green Cross names carboxymethylcellulose and "a strongly acidic cation exchanger."

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6. Claim‑by‑claim conclusion

Overall: I would expect all eighteen claims to be rejectable under § 103 over the record of this page. Claim 1 is the weakest link for the patentee, and it is also the claim the dependent claims add nothing patentable to.

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7. Anticipated patentee arguments — and why they likely fail

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8. Secondary considerations (Graham factor 4)

• Long‑felt need / recognition of the problem: There was genuine, documented need for homogeneous IFN‑γ for clinical and structural work (Langford's abstract says so explicitly). But that need is evidence of the problem, not of nonobviousness — and it cuts against the patentee, because the art identified the same need and the same route.
• Unexpected results: None evidenced. The single asserted advantage (stability) is hedged with "believed to" and is contradicted by the art's recovery data.
• Commercial success: The patent lapsed for failure to pay maintenance fees effective April 5, 1992 (a fact established in the earlier litigation section). This is at most weak, inconclusive evidence, and I would not press it: Rorer Biotechnology's change of name in 1987 and the lapse in 1992 may reflect corporate/portfolio decisions unrelated to the commercial value of the technology, and the ultimate commercial product was recombinant IFN‑γ (Genentech/Biogen lineage), not the natural‑product process claimed here. Any nexus argument would be difficult in either direction.
• Unexpected results / industry praise / copying / licensing: no evidence located in this record.

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9. Contradictions and defects in the record that I flagged rather than resolved

These are material because several bear directly on claim scope and on the priority date used for the §102(b) window:

1. Parent priority date conflict on the page itself. The bibliographic block lists US 4,382,027 (parent Ser. No. 293,775) with priority 1981‑08‑18; the "Related Parent Applications" table on the same page lists that parent with priority 1981‑04‑17 and filing 1981‑08‑18. These cannot both be right. It does not change the §103 outcome here (all record references predate even April 1981), but it would matter in a real proceeding.
2. Citation errors in the patent's own Background:

• Langford is printed on the page as "Injection and Immunity" (twice) — the journal is Infection and Immunity.
• de Ley is printed as vol. 10, pp. 877–833 (inverted/wrong); the article is 877–883.
• Wiranowska‑Stewart is cited to "Molecular Immunology, Vol 12, pp. 625‑623" (inverted page range) — a citation that cannot be verified as printed.
  These defects weaken the form of the admissions but do not erase their substance (the characterizations themselves are accurate as to Langford, de Ley, and Yip).

1. Internal inconsistency on the cation‑exchange eluent. The Detailed Description says elution with "10 mM tris‑HCl, pH 9.5 containing 50 mM sodium chloride"; Example 1 says "20 mM tris‑HCl"; claim 1 recites "20 mM tris‑HCl"; claim 16 recites "about 10 mM" for the buffered solution. This matters twice: (i) claim 1's "20 mM" limitation may lack commensurate written description; (ii) it demonstrates that the pH/concentration parameters were regarded by the applicant as non‑critical — which undercuts any nonobviousness argument built on those parameters.
2. Gel‑filtration resin inconsistency. The Detailed Description and Example 1 use Bio‑Gel P‑100/P‑150; Table I reports the step as "AcA54" (Ultrogel AcA 54 — i.e., the Langford 1979 resin), and US 4,382,027's equivalent table also shows AcA54. If the applicant's best‑mode data were in fact generated on the prior art's own gel‑filtration medium, that strengthens the obviousness case considerably. This should be resolved from the prosecution history before relying on it.
3. Claim‑drafting errors: claim 1 recites "Controlled Pure Glass beads" (elsewhere "Pore"); claim 17 recites "in step (c) said gel‑filtration treatment" although gel filtration is step (e); "Procian Red‑agarose" (Procion). I read these literally as they appear; none changes the §103 outcome, but claim 17's misdirection is a § 112(b) problem in its own right.
4. Unexamined family documents. I encountered EP 0 063 482 A2 (description closely paralleling US 4,440,675, including the same five‑step sequence) and EP 0 137 691 A1 ("Production of immune interferon and its mRNA"), whose claim 1 recites the US 4,440,675 purification sequence in characterizing‑clause format together with an unrelated induction feature. This suggests a live priority/family or interference‑type relationship. I could not verify the relationship, assignee, or priority chain, so treat this strictly as an unverified lead, not as a finding.
5. Unverified prior art: the three Chemical Abstracts citations on the page (91:209059z; 92:39568r; 93:130300d) were not resolvable in my searches. They were cited by the examiner and may contain additional § 103 teachings, but I decline to characterize them.
6. Prosecution thinness. Only one patent reference (Green Cross) and six NPL items were of record for an eighteen‑claim, five‑stage process case. That is unusually light art for this subject matter; the search results above show that US 4,168,261 (CPG chromatography of interferon) and additional 1979–1981 IFN‑γ purification literature existed — and, importantly, that O'Malley's chapter (already of record!) expressly teaches Con A‑agarose, dye‑ligand agarose, and phenyl‑agarose chromatography of human immune interferon, which alone maps onto claims 1(b), 1(c) and 18. The allowance is, on this record, hard to justify.

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10. Bottom line

US 4,440,675 is, on its own record, an obvious combination. The claimed process is a serialization of purification techniques that the prior art had individually applied to this exact protein (human immune interferon from mitogen‑induced human leukocytes) and, in Yip's case, had already serialized three of the five steps in the claimed order. The only genuinely new element — ammonium sulfate as the CPG eluent, in place of ethylene glycol — is a routine substitution within a class of inorganic‑salt eluents that the examiner‑cited Green Cross patent expressly discloses (0.5–2 M, pH 5–10), and the applicant's stated justification for the substitution is (a) a process‑engineering convenience the art already advocated and (b) an admittedly speculative ("is believed to") stability benefit that the art's own ≥100% recovery data contradict.

Identified §103 combinations, in order of strength:

1. Langford 1979 + Yip 1981 + O'Malley 1981 + US 4,314,935 (+ routine knowledge of ion exchange and size‑exclusion chromatography) → claims 1, 2, 3, 7–18.
2. de Ley 1980 + Yip 1981 + O'Malley 1981 + US 4,314,935 → same claims; this combination is preferable if the examiner wants the exact PBS/high‑salt wash sequence and the gel‑filtration MW data in the primary reference.
3. O'Malley 1981 alone (in further view of the above) → claim 18 (phenyl‑Sepharose) and the dye‑ligand alternative of claim 1(c).
4. Applicant's own specification admissions + any one of the above → claims 2–5 (order/continuity), on the strength of "the order of purification steps… is not critical" and "may be carried out prior to."

Confidence: high on the legal framework and on the mapping of claims 1–5, 8, 10–18; moderate on claim 6 (the tris/RBC pretreatment — I would want the parent US 4,382,027's full text and the prosecution history to confirm what was taught when); low/unknown on whether the three Chemical Abstracts add anything, because I could not retrieve them.

What I would verify before filing anything formal: (i) the full texts of Langford, Yip, and de Ley to confirm the wash and elution conditions I have attributed to them from abstracts and methods excerpts; (ii) the O'Malley chapter body (I have only the publisher's summary, which is nonetheless probative and explicit about Con A‑agarose, Cibacron Blue F3GA‑agarose, and phenyl‑agarose); (iii) the three Chemical Abstracts; (iv) whether the Example 1 data were generated on AcA 54 or Bio‑Gel P‑100; and (v) the true priority chain of the parent Ser. No. 293,775, given the 1981‑04‑17 vs. 1981‑08‑18 conflict on the page itself.