US 5981216

I'll search for authoritative information on US 5981216, including any 2026 CAFC docket activity.

Let me check the litigation reference found on the patent page and confirm no 2026 CAFC activity.

US 5,981,216 — Analyst Summary

Important caveat up front: I do not have direct API access to USPTO PatentCenter, PACER, or the CAFC docket system. This summary is built from the authoritative full patent text supplied in the prompt (Google Patents mirror of the USPTO record), plus corroborating web results (Justia, Darts‑ip/Unified Patents litigation metadata). Where the sources disagree, I flag it.

Bibliographic data

Prosecution chain (from the patent's own text): this is a division of Ser. No. 07/701,374 (filed 1991‑05‑13), which is a continuation of Ser. No. 06/939,130 (filed 1986‑11‑24, abandoned), which is the National Stage entry of PCT/GB86/00187 (filed 1986‑04‑01). Family members include GB 2183662, EP 216846, AU 8656665, JP 62‑502377, CA 1319120, DE 3668186, RU 2079553.

Discrepancy to note: the Unified Patents litigation database snippet lists the '216 priority date as 1985‑03‑31, whereas Google Patents (and the patent's own priority/UK filings) state 1985‑04‑01. I report both literally rather than correcting either. I have not verified which date the USPTO's official records carry.

Abstract (verbatim, with the source's own spellings preserved)

"A myeloma cell-line transformed with a vector including a gene coding for a eukariotic polypeptide and a non-immunolglobulin promoter such that expression occurs of the gene coding for the eukariotic polypeptide, directed by the non-immunoglobulin promoter. The promoter may be a viral promoter, such as an SV40 promoter, a Rous sarcoma virus long terminal repeat or a Moloney murine leukemia long terminal repeat, or a non-viral promoter such as the mouse metallothionein promoter. Rat and mouse host myeloma cell-lines such as the rat YB/2/3.0 Ag20 hybridoma, the mouse SP-20 Ag hybridoma and the mouse NSO hybridoma are employed. The production of tissue plasminogen activator (tPA) is exemplified."

Note the source text contains the typo "Simian virus 140 (SV40)" in the specification body; I preserve it as written rather than correcting it.

Claims — plain-language overview

The granted patent has one independent claim (claim 1) and nine dependent claims (2–10). Notably, the granted claim set is process-only — the "transformed myeloma cell-line" of the abstract and the original British priority application does not appear as a granted composition claim in this US grant.

Independent claim 1 — A process for producing a eukaryotic polypeptide at a level greater than 1 milligram per liter, comprising two steps:

1. Transforming a cell line with a vector that has a viral promoter operably linked to a gene coding for the eukaryotic polypeptide, where:
   • the cell line is one of YB2/3.0‑Ag20, SP2/O‑AG14, or NSO; and
   • the viral promoter is one of a Rous sarcoma virus long terminal repeat (RSV LTR), a Moloney murine leukaemia virus long terminal repeat (MoMLV LTR), or a Simian virus 40 late promoter; and
2. Culturing the transformed cells under conditions such that the gene is expressed and the polypeptide is produced in the cells.

So claim 1 is a two-dimensional (host × promoter) selection with an express >1 mg/L yield floor — a numerical limitation that reads on commercial-scale productivity, not merely on detectability.

Dependent claims 2–10 narrow claim 1 by picking specific host/promoter pairings:

• Claim 2 – promoter is the RSV LTR.
  • Claim 3 – RSV LTR + host YB2/3.0‑Ag20.
  • Claim 4 – RSV LTR + host SP2/O‑Ag14.
• Claim 5 – promoter is the MoMLV LTR.
  • Claim 6 – MoMLV LTR + YB2/3.0‑Ag20.
  • Claim 7 – MoMLV LTR + SP2/O‑Ag14.
• Claim 8 – promoter is the SV40 late promoter.
  • Claim 9 – SV40 late promoter + YB2/3.0‑Ag20.
  • Claim 10 – SV40 late promoter + SP2/O‑Ag14.

No dependent claim depends on any other dependent claim, and no NSO-specific dependent claim is present, even though NSO is recited in claim 1.

Specification highlights relevant to the claims

The working examples support the claim limitations:

• Rat YB2/3.0‑Ag20: pPRI (RSV LTR) max ~900 U/ml; pAC6 (RSV LTR) ~200 U/ml; pAC1 (MoMLV LTR) 50 U/ml; pRSD3 (RSV LTR) 45 U/ml; p6 gpt (SV40 late) 6.6 U/ml.
• Mouse SP2/O‑Ag14: pAC1 (MoMLV LTR) 50 U/ml; pAC6 (RSV LTR) ~10 U/ml.
• Mouse NSO: p6GD (SV40 late) up to 27 U/ml.
• dhfr/methotrexate co-amplification raised YB2/3.0‑Ag20/pRSD3 clone yields from 45 U/ml (150 nM MTX) to 5,800 U/ml (3 µM MTX).
• Transient-assay promoter rankings differed between the rat line (RSV LTR > SV40 late > MoMLV LTR > MMT) and the mouse lines (SV40 late > RSV LTR > MoMLV LTR > MMT) — the basis for the claim's host×promoter pairings.
• A comparative example using an immunoglobulin promoter/enhancer gave only MMT-comparable (low) expression, undergirding the "non-immunoglobulin promoter" framing.
• Airlift-fermenter run with pPRI 1/10 reached ~42 µg/ml (fibrin agar) / ~38 µg/ml (ELISA).

The specification also names other constructs (p6, p3.16, pRSV3, pZAP7, pAC2, pAC5, p6GD) and cell lines deposited with the ATCC (CRL 1581 = SP2/O‑Ag14, deposited 1980‑10‑22; CRL 1662 = YB2/3.0‑Ag20, 1982‑03‑19; TIB 18 = P3/NS1/1 Ag4.0, 1981‑11‑10), with the express disclaimer that "the cell-lines were not deposited by the applicants."

Litigation / CAFC 2026 check

• No CAFC 2026 docket activity for US 5,981,216 was found. My searches surfaced other Federal Circuit matters (e.g., ironSource v. Digital Turbine; Receivership Estate of AudienceScience v. Google; Nintendo v. American GNC), none involving this patent. This is consistent with the patent having expired 2016‑11‑09.
• The Google Patents page carries litigation metadata for a US case filed in the Maryland District Court, case 8:07‑cv‑03177, and a Darts‑ip worldwide-family litigation link.
• Corroborating 2007 activity: Lonza Group AG v. Northwest Biotherapeutics, Inc., No. 1:07‑cv‑00467‑GMS (D. Del., filed 2007‑07‑27), asserting the '216 patent together with U.S. Patents 5,122,464; 5,591,639; 5,658,759; 5,770,359; 5,827,739; 5,879,936; and 5,891,693, against Northwest's DCVax® products. The Delaware AO‑120 filing lists the '216 holder as Alusuisse Holdings A.G. I could not retrieve the outcome of either the Delaware or the Maryland action from the sources available to me.
• Note also a 2025–2026 Lonza-related docket exists (ToolGen, Inc. v. Vertex Pharmaceuticals et al., D. Mass. 1:25‑cv‑13441; ToolGen v. Lonza, Rechtbank Den Haag, Sept. 2026) — but this concerns CRISPR/Cas9 patent EP 4 357 457 and is unrelated to US 5,981,216. I mention it only to rule it out as a false positive.

Uncertainty statement

• I could not directly query the USPTO PatentCenter or CAFC/PACER dockets; the absence of 2026 CAFC activity for '216 is an absence of evidence in the sources I could reach, not a certified negative.
• The priority date differs between sources (1985‑04‑01 vs. 1985‑03‑31); I have not resolved which is controlling.
• Google Patents' assignee list ("may be inaccurate") shows a chain of re-assignments through 2014; the Darts‑ip/Unified Patents records show the same assignee set. I cannot independently verify current ownership beyond these listings.
• The title and abstract as published describe a transformed cell line, but the granted claims are exclusively process claims; the reason (e.g., a reissue, or withdrawal/superseding of composition claims during prosecution or in an earlier family member) is not evident from the text I have and I do not speculate.

Primary sources: https://patents.google.com/patent/US5981216/en ; https://patents.justia.com/patent/[5981216](/patent/5981216) ; https://portal.unifiedpatents.com/litigation/Maryland%20District%20Court/case/8%3A07-cv-03177 ; https://patentdocs.org/2007/08/05/court-report-43/

I'll research litigation involving US patent 5981216. Let me run several searches.

Let me dig into the litigation lead from the Google Patents record.

I found the primary case. Let me get more detail on the parties, dates, and outcome.

Summary of findings for U.S. Patent No. 5,981,216

Bottom line: One litigation matter is documented in which U.S. 5,981,216 was asserted — Lonza Group AG v. Northwest Biotherapeutics, Inc. (D. Md. No. 8:07-cv-03177). I found no other suits, no IPR/PGR proceedings, and no Federal Circuit appeals specifically involving this patent. Details below, with sources.

Case 1 — Lonza Group AG v. Northwest Biotherapeutics, Inc.

Key sources

• Google Patents litigation entry for US5981216A (links the Maryland case): https://patents.google.com/patent/US5981216A/en — the record shows "US case filed in Maryland District Court" with case 8:07-cv-03177.
• Docket listing (parties, cause of action "35 U.S.C. § 271 Patent Infringement"): https://dockets.justia.com/search?nos=830&cases=mostrecent&min-day=1&min-month=1&min-year=2004&max-day=21&max-month=11&max-year=2009&page=7&noscat=10&state=maryland — "Lonza Group AG v. Northwest Biotherapeutics, Inc., as 8:2007cv03177."
• Lonza/NWBT press release (Biospace, Dec. 20, 2007) describing the amended complaint and the withdrawal of the non-Prostate claims: https://www.biospace.com/lonza-group-ltd-withdraws-majority-of-claims-in-patent-lawsuit-against-northwest-biotherapeutics

Preceding related action — Delaware (companion filing)

The Maryland suit was a refiling of an earlier Lonza action against the same defendant:

• Court: U.S. District Court for the District of Delaware
• Filed: reportedly July 27, 2007 (per Lonza/NWBT's Dec. 2007 press release)
• Case number: not identified in the sources I retrieved
• Status: Dismissed by agreement — Lonza agreed to dismissal of its entire complaint, and NWBT agreed to dismissal of its answer and counterclaims (which included Delaware Deceptive Trade Practices Act, unfair competition, tortious interference, and abuse-of-process claims seeking treble and punitive damages). Lonza simultaneously filed the Maryland action.
• I could not confirm whether U.S. 5,981,216 specifically was among the patents asserted in the Delaware pleading; the press release describes the asserted patents generally as "certain gene expression technology patents."

Other data points worth noting

• Google Patents "First worldwide family litigation" link points to Darts-IP family ID 27262637, indicating litigation was also filed within the broader patent family (not necessarily on the '216 patent itself): https://patents.darts-ip.com/?family=27262637
• No IPR/PGR/appeal for '216 found. My searches surfaced PTAB and Federal Circuit activity for other patents (e.g., the '599 patent IPRs involving Facebook/Twitter/Snap, and the Amgen v. Roche EPO patents '008/'868/'698), which are unrelated and I am deliberately excluding.
• Patent status: Expired – Lifetime; anticipated expiration November 9, 2016 (per Google Patents). Current listed assignees: Healthcare Royalty Partners II LP; Lonza Licences AG; Lonza Swiss Licences AG.

Caveats

1. Identifier discipline: I limited results to U.S. 5,981,216. Search hits containing "5981216" as an unrelated string (e.g., a Peruvian Supreme Court notification number, "2015 5981216") were excluded as false positives.
2. Unverified outcome: The single most important gap is the final disposition of D. Md. 8:07-cv-03177. To confirm it, PACER and Bloomberg Law/RECAP (CourtListener) docket access for that case number would be needed; the case is old enough that public litigation databases may have purged or paywalled the docket. I recommend not representing any outcome for this case without pulling the docket.
3. The July 27, 2007 Delaware filing date comes from a party press release, and the Nov. 27, 2007 Maryland filing date comes from a secondary litigation-reporting source (patentdocs, as republished on a message board), not a primary court record — treat both with mild caution.

I'll verify the ODP default against public sources before concluding.

Let me confirm there's no PTAB activity indexed elsewhere and check the litigation context.

Proceedings overview

Total AIA trial proceedings on US 5981216: 0. The USPTO Open Data Portal returns no IPR, PGR, or CBM for this patent, and my independent web checks surface no PTAB proceeding either. Breakdown: active — 0; claims invalidated — 0; claims sustained — 0; settled — 0; institution denied — 0. The bottom line for a defendant: there is no PTAB track record to exploit and no estoppel to rely on — but that is mostly a function of timing and subject matter, not of the patent having been "tested and survived." This is a 1985-priority biotech patent that already expired on 2016-11-09; the absence of IPRs is the expected result of an expired, non-CBM-eligible patent, not evidence that the claims are hardened. Do not treat "no IPRs" as a validity endorsement.

PTAB proceedings

No AIA trial proceeding has been identified on file for US 5981216 (no IPR, no PGR, no CBM). Concretely, the searches I ran returned:

• Zero PTAB petitions naming the '216 patent as the challenged patent.
• Zero Final Written Decisions citing the '216 patent as the patent at issue.
• Zero PTAB appeals to the Federal Circuit arising from a '216 proceeding.

I am not going to invent proceeding numbers, panels, or outcomes to fill this section. If your adversary's demand letter or an old litigation filing claims an IPR "invalidated" or "upheld" these claims, that claim is not supported by anything in the public record I can find — ask for the proceeding number and pull it on PTAB E2E before you respond.

Two structural reasons explain the empty docket, and both matter to your defense:

• Subject-matter gate. CBM review under AIA § 18 was limited to "covered business method" patents (financial-services practice). A myeloma/hybridoma expression-vector patent is not CBM-eligible, so that avenue never existed.
• Expiration. The structured record lists the legal status as "Expired - Lifetime," with an anticipated expiration of 2016-11-09. The AIA trial regime only began 2012-09-16, giving roughly a four-year window (2012–2016) in which an IPR/PGR could realistically have been sought during the patent's life. No one filed. Post-expiration, the Board will generally only institute where a petitioner shows a concrete, live controversy — a bar most challengers choose not to litigate.

Related district-court activity (context, not PTAB)

The structured data flags this family as having litigation, and the Google Patents page cites Maryland District Court case 8:07-cv-03177. Separately, a 2007 Delaware action, Lonza Group AG v. Northwest Biotherapeutics, Inc., 1:07-cv-00467 (D. Del., filed 2007-07-27), asserted a portfolio that included the '216 patent (alongside U.S. 5,122,464; 5,591,639; 5,658,759; 5,770,359; 5,827,739; 5,879,936; and 5,891,693). These are federal infringement actions, not AIA trials, and I have not verified their dispositions — treat the docket links as leads, not conclusions.

One caution on sourcing: the Google Patents page attributes its litigation data to "Unified Patents Litigation Data." That is a data-source credit, not evidence that Unified Patents (the defensive aggregator) filed anything against this patent. Do not read a defensive-aggregator challenge into that attribution.

Strategic summary

Claim status — all UNTESTED, and now expired. The '216 patent issued with claims 1–10, all of them drawn to a process for producing a eukaryotic polypeptide (claim 1 recites a level "greater than 1 milligram/liter" and a host cell selected from YB2/3.0-Ag20, SP2/O-Ag14, and NSO, with a viral promoter selected from the RSV LTR, MoMLV LTR, and SV40 late promoter). Because no IPR ever ran, there are no canceled claims, no substitute claims, and no claim-level validity holdings — the claims are UNTESTED, not SUSTAINED. The only "narrowing" on this record is the ordinary prosecution path: the patent is a division of Ser. No. 07/701,374 (filed 1991-05-13), itself a continuation of Ser. No. 06/939,130 (filed 1986-11-24), the national-stage entry of PCT/GB86/00187 (filed 1986-04-01), and the granted claims are far narrower than the original disclosure's broad "non-immunoglobulin promoter" genus (the MMT promoter and Ig promoter/enhancer constructs described in the spec are not recited in the issued claims). If you are accused today, the live question is claim scope and infringement, not validity that the PTAB already resolved — because it did not.

Estoppel landscape — none, in either direction. Because there was no IPR/PGR, § 315(e)(2) estoppel never attached, and no petitioner or privy is barred from anything. For a defendant, that cuts both ways: you face no estoppel, but you also get no benefit from an earlier petitioner's work product or from a prior FWD's claim construction. Every invalidity ground — § 102, § 103, and § 112 (including written-description/enablement attacks on the breadth of the "greater than 1 mg/L" functional limitation) — remains fully available in district court or in an ex parte reexamination. Practically, the most useful defensive posture against an expired patent is not invalidity but non-infringement/claim construction and, more decisively, the expiration date itself: with the patent expired since 2016-11-09, damages exposure is limited to the six-year lookback under § 286 for past acts, and any injunctive demand is moot.

Pattern signals. No repeat petitioner, no serial-filing signature, no patent-owner PTAB-appeal pattern, and no defensive-aggregator chain — for the simple reason that there is no PTAB activity at all. The owners of record (Healthcare Royalty Partners II, L.P. and the Lonza licensing entities) appear in this family as royalty/licensing holders, which is consistent with the 2007 assertion campaigns rather than with sustained PTAB warfare.

Recommended next steps

• If you are a defendant and someone asserts the '216 patent now: lead with expiration (anticipated expiration 2016-11-09; status "Expired - Lifetime"). Before negotiating anything, demand the specific asserted claim numbers and the six-year damages window under 35 U.S.C. § 286. There is no FWD to link or quote here — the patent has never been before the PTAB — so any assertion that "the claims were invalidated" or "survived IPR" is unsupported; verify on PTAB E2E and via USPTO PatentCenter.
• Do not build a defense on PTAB estoppel. With zero proceedings, there is no estoppel record to leverage and no prior art that a petitioner has already "used up."
• If you nonetheless want a validity anchor (e.g., for a declaratory-judgment posture or a license negotiation), the strongest levers remain the pre-1986 art of record and the functional ">1 mg/L" claim language; an ex parte reexamination is the only realistic PTAB-adjacent route, and even that is discretionary and largely moot against an expired patent.
• No trial-stage milestones to track. There are no pending institution deadlines, oral hearings, or statutory one-year FWD dates, because there are no pending proceedings. If a petition is filed hereafter, it would be a genuinely new development — flag it immediately, but the default assumption for this patent should remain "no PTAB activity on file."

Sources: Google Patents, US5981216A (structured "PTAB proceedings on file" data, claims 1–10, priority/filing/grant/expiration dates, litigation links); PTAB E2E and USPTO ODP for proceeding search; D. Del. 1:07-cv-00467 docket report (Lonza v. Northwest Biotherapeutics, portfolio including the '216 patent).

I'll research the assignment record for US 5981216, cross-referencing the USPTO Assignment Center, litigation records, and the parties involved.

I found the key litigation (Lonza Group AG v. Northwest Biotherapeutics, 8:07-cv-03177). Now let me dig into the assignment records and the unusual Pharmathene/MPM security agreement entry.

Now let me verify the corporate history (Celltech → Alusuisse/Lonza), the inventors' employer, and try to pin down reel/frame numbers.

Assignment & Ownership Analysis — US 5981216

Source note / data limitation (read first): The authoritative records here are the USPTO Assignment Center records (also surfaced via Google Patents' "Reassignment" legal-events table and via Unified Patents' patent page for US‑5981216‑A). I was able to retrieve the event chain, conveyance types, assignors/assignees and dates, but I was not able to retrieve reel/frame numbers or the correspondent (recording attorney) of record from the sources accessible to me. I have not fabricated those fields — where they are missing I say so. Treat the reel/frame and correspondent fields below as unverified. Verify at the USPTO Assignment Center by searching patent number 5981216.

Inventors

Two named inventors. The application traces to GB priority 1985‑04‑01 (GB8508442) and 1985‑09‑03 (GB8521815), with the PCT (PCT/GB86/00187) filed 1986‑04‑01; the US national-stage entry (06/939,130, filed 1986‑11‑24) was abandoned in favor of a 1991‑05‑13 continuation (07/701,374), which was in turn divided into the present application 08/483,813 (filed 1995‑06‑07) and granted 1999‑11‑09.

Unusual pattern — noted, but not a fire-sale tell: The grant is ~14 years after the 1985 priority date, reflecting an unusually long continuation/division chain (abandoned national-stage → 1991 continuation → 1995 division). The ownership change that eventually moved this family did not follow inventor departure — the assignment came ~11 years after filing and was a corporate divestiture of Celltech's biologics/cell-line business, not an inventor-driven event. I found no evidence in the accessible record of either inventor leaving within 12 months of filing.

Original assignee

• Entity named at grant: Alusuisse Holdings AG (Google Patents "Original Assignee"). The true original applicant/owner was Celltech Limited, renamed Celltech Therapeutics Limited, which assigned the case to Alusuisse Holdings A.G. in 1997 (before grant).
• What it was / current status: Celltech was a UK biotechnology company that pioneered mammalian cell-line expression technology, including the glutamine synthetase (GS) expression system — of which US 5981216 is a foundational member (Lonza's own patent schedule, in the Leap Therapeutics license appendix, titles this family "Transformed Myeloma Cell-Line…", ref. L.B.P.07 (PA 98), registered owner Lonza Group AG). Celltech's biologics assets passed to the Alusuisse‑Lonza group, which became Lonza Group AG.
• Product/embodiment: This is not a drug patent; the claims cover a process for producing polypeptides (>1 mg/L) in transformed myeloma/hybridoma hosts (YB2/3.0‑Ag20, SP2/O‑Ag14, NSO) using RSV LTR, MoMLV LTR or SV40‑late promoters. The commercial embodiment is the Lonza GS System / GS expression platform, which Lonza licenses commercially (it is still cited as a standard expression vector system in current antibody patent filings).
• Status: Operating. The Lonza group (Lonza Group AG; Basel) remains an active operating company (biologics CDMO / specialty ingredients). The patent itself expired 2016‑11‑09 ("Expired – Lifetime," anticipated expiration). Ownership/security interests now sit with Lonza Licences AG, Lonza Swiss Licences AG, and Healthcare Royalty Partners II, L.P.

Assignment timeline

Chronological. Reel/frame and correspondent fields could not be retrieved and are marked accordingly. Dates below are the recording/event dates as reported in the assignment-derived legal events table; execution dates were not separately disclosed in the sources retrieved.

• 1997‑11‑05 (recorded) — Reel/frame not retrieved

  • Conveyance: Assignment of assignors' interest
  • Assignor: Celltech Therapeutics Limited (formerly "Celltech Limited")
  • Assignee: Alusuisse Holdings A.G.
  • Correspondent: not retrieved
  • Context: Corporate divestiture — Celltech's biologics/cell-line (GS system) business transferred into the Alusuisse‑Lonza group.

• 2001‑07‑23 (recorded) — Reel/frame not retrieved

  • Conveyance: Assignment of assignors' interest (and a parallel Merger record, same date)
  • Assignor: Alusuisse Lonza Group AG
  • Assignee: Lonza Group AG
  • Correspondent: not retrieved
  • Context: Internal reorg — group rename/merger consolidating the Alusuisse‑Lonza entities into Lonza Group AG.

• 2006‑08‑01 (recorded) — Reel/frame not retrieved — ⚠️ ANOMALY

  • Conveyance: Security agreement
  • Assignor: Pharmathene, Inc.
  • Assignee: MPM BioVentures III‑QP, L.P., as Administrative Agent
  • Correspondent: not retrieved
  • Context: Apparent data mis-association. Pharmathene (a US biodefense company) and MPM BioVentures III (a venture fund acting as collateral agent for Pharmathene's secured lenders) have no documented relationship to this patent, which was held by Lonza Group AG throughout 2006. This security agreement almost certainly belongs to a different Pharmathene asset; it should not be read as an ownership link in this chain. Flag for verification against reel/frame.

• 2010‑10‑22 (recorded) — Reel/frame not retrieved — two records

  • Conveyance: License and Conditional Assignment
  • Assignor: Lonza Group AG
  • Assignee: Lonza Swiss Licences AG
  • Correspondent: not retrieved
  • Context: Internal reorg — creation of an intra-group licensing vehicle within Lonza.

• 2013‑12‑27 (recorded) — Reel/frame not retrieved — three records

  • Conveyance: License; Assignment of assignors' interest (to Lonza Licences AG and Healthcare Royalty Partners II, L.P.); Security Agreement (Lonza Licences AG → Healthcare Royalty Partners II, L.P.)
  • Assignor: Lonza Group AG (assignment/license); Lonza Licences AG (security agreement)
  • Assignee: Lonza Licences AG and Healthcare Royalty Partners II, L.P.
  • Correspondent: not retrieved
  • Context: Royalty monetization / securitization. Healthcare Royalty Partners II is a royalty‑investment fund. Lonza Licences AG's registered corporate purpose (per Swiss commercial-register data) is expressly limited to holding the intercompany licence and the assigned patent/know‑how rights, with permitted encumbrances only under the "Intellectual Property Security Agreement and Pledge" with Healthcare Royalty Partners II, L.P.

• 2014‑06‑26 (recorded) — Reel/frame not retrieved — three records

  • Conveyance: Amended License; Amended Conditional Assignment (×2)
  • Assignor: Lonza Group AG
  • Assignee: Lonza Swiss Licences AG
  • Correspondent: not retrieved
  • Context: Amendment/clean‑up of the 2010 intra-group structure.

Execution dates, reel/frame numbers, and all correspondents of record are not present in the material I could access. No post‑2014 assignment is recorded; the patent expired 2016‑11‑09.

Timeline diagram

timeline
    title Ownership of US 5981216
    1985 : UK priority applications filed
    1986 : PCT filed by Celltech
    1997 : Assigned to Alusuisse Holdings
         : From Celltech Therapeutics
    1999 : Patent granted
    2001 : Alusuisse Lonza to Lonza Group AG
         : Merger and assignment recorded
    2006 : Pharmathene security recorded
         : Apparent data anomaly
    2007 : Lonza sues Northwest Biotherapeutics
    2010 : Lonza Swiss Licences gets license
    2013 : Lonza Licences AG takes assignment
         : Healthcare Royalty Partners security
    2014 : Amended license to Lonza Swiss
    2016 : Patent expires

NPE / troll-pattern signals

1. Shell-entity transfer — NOT PRESENT (with caveat). No transfer to an external licensing LLC. Lonza Licences AG and Lonza Swiss Licences AG are intra-group Lonza entities created to hold and sublicense the group's own patents (Swiss register purpose: holding the intercompany licence and assignment from Lonza Group AG). They are a structuring vehicle for a royalty financing, not an arm's-length NPE. Caveat: their registered scope is deliberately narrow (single‑purpose licensing + permitted pledges to Healthcare Royalty Partners II).

2. Known asserter in the chain — NOT PRESENT. No assignee matches Acacia, Marathon, IV, IPNav, Wi‑LAN, Conversant/Mosaid, Vringo, Pendrell, Innovatio, MPHJ, Lumen View, Round Rock, or any Erich Spangenberg entity. The chain parties are Celltech → Alusuisse/Lonza → Lonza entities → Healthcare Royalty Partners II.

3. Repeat correspondent across the chain — UNVERIFIABLE. Correspondent/recording‑attorney data was not retrievable, so I cannot confirm or refute recurrence of a single recording attorney. No finding (absence of data ≠ absence of pattern).

4. Cascading transfers through chained LLCs — NOT PRESENT. There are clustered recordings (two on 2010‑10‑22, three on 2013‑12‑27, three on 2014‑06‑26), but these span ~4 years and are successive corporate amendments of one intra‑group structure, not a sub‑24‑month chain of unrelated LLC hops.

5. Pre‑litigation transfer — NOT PRESENT. Lonza Group AG sued Northwest Biotherapeutics first in D. Del. 1:07‑cv‑00467 (filed 2007‑07‑27, asserting US 5,981,216 among eight patents) and then in D. Md. 8:07‑cv‑03177 (filed 2007‑11‑27). The nearest preceding recorded event is the 2001 Lonza Group AG merger and the (anomalous) 2006‑08‑01 Pharmathene security entry — none within 6 months of the 2007 suits, and the plaintiff was the long‑standing owner, not a fresh assignee.

6. Bankruptcy fire‑sale — NOT PRESENT. No Chapter 7/11 sale, no stalking‑horse transfer.

7. Privateering — NOT PRESENT. The inverse: Lonza asserted its own patent in its own name against a third party's contract manufacturer (Medarex) that had allegedly used the GS system. Lonza withdrew nearly all claims; the DCVax‑Prostate remnant resolved with no licence and no payment (Northwest agreed to destroy remaining PSMA inventory).

8. Defensive aggregator — NOT PRESENT. The chain does not terminate at RPX, AST, LOT, Unified or OIN. It terminates at Lonza group entities under a royalty‑financing pledge to Healthcare Royalty Partners II.

Verdict

Operating-company assertion.

The ownership chain runs from Celltech (inventors' employer) through a genuine corporate divestiture to Alusuisse Holdings AG (1997‑11‑05), then Lonza Group AG (2001‑07‑23 merger/assignment), and the patent was asserted by its owner, Lonza Group AG, in its own name against Northwest Biotherapeutics in D. Del. 1:07‑cv‑00467 (2007‑07‑27) and D. Md. 8:07‑cv‑03177 (2007‑11‑27) — an operating company enforcing its own cell‑line/expression‑technology platform, not an NPE acquiring rights to assert. The only NPE‑adjacent features are intra‑group Lonza licensing entities (2010‑10‑22, 2013‑12‑27, 2014‑06‑26) whose sole recorded encumbrance is the "Intellectual Property Security Agreement and Pledge" with Healthcare Royalty Partners II, L.P. — a royalty monetization/securitization structure, not a shell‑entity assertion play. The 2006‑08‑01 Pharmathene → MPM BioVentures III‑QP security agreement is anomalous and inconsistent with the Lonza chain and should be treated as a probable data mis‑association pending reel/frame verification; it does not change the verdict. The patent expired 2016‑11‑09, so all asserted claims have lapsed.

Verification links: Google Patents US5981216 · USPTO Assignment Center (search 5981216) · Unified Patents US‑5981216‑A · D. Md. 8:07‑cv‑03177 docket · Lonza litigation press release

Caveat restated: reel/frame numbers and correspondents of record were not retrievable from the sources available to me and are flagged not retrieved rather than estimated.

I'll research US 5981216 and each of its cited prior-art references. Let me start with searches on the patent itself and its examiner citations.

Prior-Art Analysis — US 5981216

1. Patent verified

Source: https://patents.google.com/patent/[US5981216A](/patent/US5981216A)/en (this record reproduces the USPTO front page, including the "References Cited" / "Citations" list used below).

Note on method and a limitation: I could not open a live USPTO PatentCenter/PAIR or USPTO full-text (PatFT) record for this number in the searches run; the citation set below is the USPTO examiner-cited list as reproduced on the US 5981216 record and corroborated against each reference's own bibliographic record. Where I had no reliable record of a reference's content (as opposed to its bibliographic data), I say so explicitly rather than assume.

Critical framing point: The granted claims 1–10 are all process claims — a process for producing a eukaryotic polypeptide at a level greater than 1 milligram/liter by transforming a cell line selected from the group consisting of YB2/3.0-Ag20, SP2/O-AG14 and NSO with a vector comprising a viral promoter (RSV LTR / MoMLV LTR / SV40 late promoter) operably linked to the polypeptide gene, and culturing. Several of the examiner citations were evidently directed at the originally filed claims (which recited transformed cell lines, selectable markers, amplifiable genes such as dhfr, etc.). A reference that anticipates an element of the specification does not anticipate a claim unless it discloses every limitation of that claim in a single reference. (See § 2131 / § 2132 MPEP logic.)

2. Examiner-cited patent references (the 5 "Citations")

(a) EP 0043718 A2 — closest to the cell-line limitation

URLs: http://data.epo.org/gpi/EP0043718A3-IMPROVEMENTS-IN-OR-RELATING-TO-CELL-LINES.html ; https://patents.google.com/patent/EP0043718A2/en

Anticipation analysis:

• Claims 1, 3, 6, 9 (the claim set that names YB2/3.0-Ag20 as the host) — EP 0043718 A2 supplies the host cell element and its public availability (ATCC CRL 1662), but does not disclose a vector comprising a viral promoter operably linked to a gene coding for a eukaryotic polypeptide, nor the step of transforming, nor culturing to >1 mg/L. No anticipation.
• It is nonetheless the most material reference to the cell-line genus and would have been the reference that forced the applicants off any claim to the cell line per se (consistent with the granted claims being process-only).

(b) US 4,740,461 — vectors/cotransformation/selection

URLs: https://portal.unifiedpatents.com/patents/patent/US-[4740461](/patent/4740461)-A ; https://uspto.report/patent/grant/4740461 ; https://patents.google.com/patent/KR101704893B1/en#29 (family citation record)

Anticipation analysis:

• Claims 1–10 — no anticipation. The record I retrieved does not establish that US 4,740,461 discloses (i) any of the three named host cell lines, (ii) an RSV LTR, MoMLV LTR or SV40 late promoter operably linked to a heterologous non-Ig polypeptide gene, or (iii) production at >1 mg/L.
• Relevance is to vector architecture / cotransformation / selection and subcloning biology, i.e., to the specification's selectable-marker and dhfr-amplification teachings rather than to the granted process claims. I do not have a verified full text for this reference, so this assessment is expressly provisional.

(c) US 4,663,281 — myeloma transformation with enhancer-bearing constructs

URLs: https://patents.google.com/patent/[US4663281A](/patent/US4663281A)/en ; https://www.freepatentsonline.com/[4663281](/patent/4663281).html ; https://uspto.report/patent/grant/4663281

Anticipation analysis:

• Claims 1–10 — no anticipation. US 4,663,281 teaches tissue-specific (largely immunoglobulin) enhancer/promoter expression in lymphoid/myeloma cells. The granted claims of 5981216 require a viral promoter (RSV LTR / MoMLV LTR / SV40 late) as the promoter driving the heterologous gene. The pSV2gpt construct's SV40 early promoter drives only the selectable marker (Ecogpt), not the product gene, and the reference's product gene is expressed off the Ig transcription unit. Different promoter; no single-reference disclosure of every limitation.
• This is the reference most likely to have been cited as § 102/§ 103 art against immunoglobulin-promoter-based subject matter and against the "myeloma cell line" genus. Note: US 4,663,281 is also the patent asserted in Massachusetts Institute of Technology v. Imclone Systems, Inc. (D. Mass. 1:04-cv-10884), where the specification of US 4,663,281 appears in the record (https://www.courtlistener.com/docket/[4278389](/patent/4278389)/59/2/massachusetts-institute-of-technology-v-imclone-systems-incorporated/). That litigation concerns 4,663,281, not 5981216.

(d) US 4,775,624 — heterologous polypeptide expression in eukaryotic hosts

URLs: https://patents.google.com/patent/US4775624 ; https://www.freepatentsonline.com/[4775624](/patent/4775624).html ; https://www.freepatentsonline.com/[5270178](/patent/5270178).html (family, describing US 4,775,624)

Anticipation analysis:

• Claims 1–10 — no anticipation. US 4,775,624 discloses eukaryotic expression of a heterologous (non-Ig) polypeptide generally, but the record does not tie it to the three recited host lines (YB2/3.0-Ag20, SP2/O-AG14, NSO) nor to the three recited viral promoters, and it does not disclose a >1 mg/L myeloma production level. Its relevance is the § 102(e) date proximity (a Feb-1985 US filing) and the general concept of eukaryotic expression of a non-immunoglobulin polypeptide.

(e) EP 0 255 320 A2 — not prior art to this patent

Source: listed in the "Citations (5)" table of https://patents.google.com/patent/US5981216A/en (priority 1986-07-28, publication 1988-02-03, Genzyme Corporation). I did not obtain and verify an independent full-text record for this document.

Anticipation analysis:

• None of claims 1–10. Because EP 0 255 320 A2 postdates the 1985-04-01 priority date recorded for US 5981216, it cannot anticipate under § 102. It is best understood as a contemporaneous-work reference (a same-field European filing appearing in the examiner's list), relevant at most to the state of the art/obviousness context of "expression of proteins in myeloma cells," not to anticipation. (Caveat: if the priority claim to GB 858508442A / GB 858521815A were to fail, the effective date would move and this analysis would need revisiting — but on the face of the record, the priority date stands.)

3. Examiner-cited non-patent literature (the 24 NPL citations)

These are § 102(b) printed publications and are, collectively, more threatening to individual claim elements than the patent citations:

Anticipation analysis: Even read together, these references support individual elements (RSV LTR competency; SP2/0 and YB2/3.0-Ag20 availability; gpt/neo selectable markers). Under § 102, no single one of them discloses the full claim — in particular the combination of a specified myeloma/hybridoma host with a specified viral promoter operably linked to a heterologous non-Ig polypeptide gene, let alone the ">1 mg/L" production level. They are properly characterized as § 103-type art, not § 102 anticipation art. (Gorman 1982 is the single most relevant NPL item, because it is the document the specification itself concedes describes RSV LTR as a strong promoter in other cell types — the patent's asserted inventive contribution being that RSV LTR "proves effective in a myeloma cellular environment.")

4. Bottom line

1. No cited prior-art reference anticipates any of granted claims 1–10. Anticipation requires a single reference disclosing every limitation — including the specific host-line genus (YB2/3.0-Ag20, SP2/O-AG14, NSO), a specific viral promoter (RSV LTR / MoMLV LTR / SV40 late) operably linked to the heterologous gene, and production at > 1 mg/L. None of the five patent citations and none of the 24 NPL citations does this.
2. Per-claim exposure, best available read of the record:

1. The most material single reference is EP 0043718 A2 (it discloses the YB2/3.0-Ag20 host cell that appears in claims 1, 3, 6, 9), followed by US 4,663,281 (myeloma transformation with selectable-marker constructs) and US 4,775,624 (eukaryotic expression of a non-Ig polypeptide, filed 1985-02-08 — only ~7 weeks before the 1985-04-01 priority date).
2. EP 0 255 320 A2 (Genzyme) is not prior art to this patent on the recorded dates and cannot support an anticipation position.
3. Caveats I want on the record: (i) I did not verify the full texts of US 4,740,461 or EP 0 255 320 A2 and therefore qualified those assessments; (ii) my analysis uses the citation list reproduced from the US 5981216 front page rather than a live USPTO PAIR/PatentCenter fetch; (iii) the 1995 filing date and 1999 grant date mean the applicable novelty statute is pre-AIA 35 U.S.C. § 102, and the specific § 102(e) dates depend on the parent/priority chain (PCT/GB86/00187, filed 1986-04-01; GB 8508442, 1985-04-01; GB 8521815, 1985-09-03) — the second GB priority date (1985-09-03) could matter for later-added subject matter and would need to be checked against the as-filed disclosure before relying on the 1985-04-01 date for every limitation.

I'll verify the cited prior-art references before building the §103 analysis.

Obviousness Analysis — US 5,981,216 under 35 U.S.C. § 103

Scope note / assumptions. US 5,981,216 claims priority to GB 8508442 (1985‑04‑01) via PCT/GB86/00187 (filed 1986‑04‑01), US 06/939,130 (1986‑11‑24), and divisional US 07/701,374 (1991‑05‑13). Because the priority date predates the AIA, pre‑AIA § 103 applies, with Graham v. John Deere as the framework and KSR v. Teleflex informing the "obvious to try" analysis. I rely on the prior‑art table on the patent page (https://patents.google.com/patent/US5981216/en) plus verification of individual references noted below. I could not verify the substance of every cited item, and I have not verified the outcome of the Maryland litigation (8:07‑cv‑03177) referenced on the page.

1. The claim at issue

Only claim 1 is independent. Its elements are:

Claims 2–10 are pure species claims: claim 2 (RSV LTR), 3 (RSV + YB2/3.0‑Ag20), 4 (RSV + SP2/O‑Ag14), 5 (MoMLV), 6–7 (MoMLV + rat/mouse line), 8 (SV40 late), 9–10 (SV40 late + rat/mouse line). Each is a single‑reference or two‑reference combination of the same two variables; if claim 1 falls, they fall a fortiori.

2. What the art of record discloses

Admissions in the '216 specification (usable as prior art under § 103): the Background states that myeloma vectors of the prior art "also include selectable markers … The markers comprise viral promoters driving expression of prokaryotic genes … which confer antibiotic resistance." That is an express admission that a viral promoter (SV40 early) already functioned in myeloma cells, and that myeloma cells were already a recognized recombinant‑DNA host. The Background further concedes that the field already knew how to make chimeric immunoglobulins in myeloma cells, and cites US 4,419,446 for transforming mouse fibroblasts with a human insulin gene.

3. Combinations that render claim 1 obvious

Combination A — RSV LTR in a myeloma line (claims 1–4).
US 4,472,500 / EP 0043718 A2 (the YB2/3.0.Ag.20 cell line, expressly adapted to culture for producing secreted protein) + Shulman (SP2/O‑Ag14) + Gorman et al. 1982 (RSV LTR is a strong promoter in a variety of eukaryotic cells) + Southern & Berg / Mulligan & Berg (neo, gpt cassettes to recover stable transformants).

Motivation: the artisan had (i) a well‑characterized, non‑Ig‑secreting, high‑clonability myeloma host line and two well‑characterized mouse myelomas, (ii) an identified strong, broadly functional viral promoter, and (iii) off‑the‑shelf dominant selection markers. The commercial driver — producing a cloned secreted human protein such as tPA at scale (Pennica et al. 1983 cloned tPA cDNA and expressed it in E. coli) — supplied a "design need … and market pressure." Substitution of the RSV LTR for the Ig promoter in a myeloma host is an obvious expedient: the RSV LTR was known to work in mouse cells, and the specification's own admission shows viral promoters already operated in myeloma cells.

Reasonable expectation of success: high. The only genuinely open question was the magnitude of expression, not whether expression would occur — and Gorman framed the RSV LTR as a "strong" promoter generally, not cell‑restricted.

Combination B — MoMLV LTR in a myeloma line (claims 1, 5–7).
Perkins et al. 1983 + Hoffmann et al. 1982 + cell‑line references (EP 0043718 A2 / Shulman) + selection markers. Perkins expressly teaches retrovirus‑derived vectors exploiting the MLV LTR for expression of exogenous genes in mammalian cells; Gorman teaches interchangeable use of a retroviral LTR. Motivation: the two best‑characterized retroviral LTRs (RSV, MLV) were interchangeable, mutually obvious alternatives — the paradigm of "a finite number of identified, predictable solutions" (KSR, 550 U.S. at 421).

Combination C — SV40 late promoter in a myeloma line (claims 1, 8–10).
Southern & Berg (pSV2 vectors; SV40 promoter/neo) + US 4,740,461 (direct ligation of eucaryotic promoters to product and selection genes; yield‑by‑subcloning) + US 4,775,624 (eukaryotic expression vectors listing RSV LTR, MSV LTR, SV40 promoter and dhfr amplification, with myeloma‑type hosts) + Shulman / NSO. Motivation: the SV40 promoter system was the archetypal mammalian expression cassette, and the '216 Background admits SV40‑driven cassettes already worked in myeloma cells. Selecting the late SV40 promoter over the early SV40 promoter is the routine screening of a small number of known promoter variants — a classic "obvious to try" case with predictable results.

Combination D — the "finite options" overlay. Claim 1 is a 3 × 3 Markush: three known host lines × three known strong promoters. The patent itself concedes that promoter preference had to be ranked empirically in a transient fibrin‑overlay assay ("The results from these transfections demonstrated that … promoters were ranked …"; "one may find differences between results from transient and stable cell‑lines"). Where the art identifies a small, closed set of candidates and the specification reaches its answer by routine screening, § 103 is met.

4. The "greater than 1 milligram/liter" limitation does not save the claim

1. Recitation of an inherent result. Where a claim differs from the prior art only in a recited result of the same process, the result is not patentable: "newly discovered results of known processes directed to the same purpose are not patentable because such results are inherent," PAR Pharm., Inc. v. TWI Pharms., Inc., 773 F.3d 1186 (Fed. Cir. 2014); In re Kratz, 592 F.2d 1342 (CCPA 1979). The recited >1 mg/L threshold is a result‑effective quantity obtained by practising the same transformation/culture steps the art discloses.
2. No conversion, no measured threshold. The specification reports only units/ml for every cell line (pAC1 = 50, pAC6 = 200, pPRI = 900, p6gpt = 6.6, pRSD3 = 45, p6GD "positive") and never ties those figures to mg/L. The only mg/L‑equivalent figure (42 µg/ml = 42 mg/L) comes from a fed‑batch airlift run of one clone, pRI 1/10, and largely reflects dhfr/methotrexate co‑amplification (45 U/ml → 5,800 U/ml over five months) — a step not required by claim 1. The claim's nexus to the asserted result therefore rests on the prior‑art‑disclosed elements themselves.
3. The threshold is not met across the claimed scope. The specification's own example for the claim 9 combination (YB2/3.0‑Ag20 + SV40 late, p6gpt) is 6.6 U/ml — orders of magnitude below 1 mg/L — showing the recited level is a result‑effective variable to be optimized, not a distinctive feature of the claimed genus. (This also raises an independent § 112(a) written‑description question for the full scope, relevant to how a challenger would plead.)

5. No persuasive secondary considerations

• No comparative data against the closest art (viral promoter in a myeloma host) showing superiority; the specification instead shows a host‑dependent ranking (RSV LTR > SV40 late > MoMLV > MMT in the rat line; SV40 late > RSV > MoMLV > MMT in the mouse lines) — exactly the host‑dependence Gorman would predict, and the ordinary outcome of routine screening.
• The assertion that it is "entirely unexpected that the RSV LTR proves effective in a myeloma cellular environment" is conclusory and self‑contradicted by the Background admission that viral promoters were already driving selectable markers in myeloma cells, and by US 4,663,281's teaching that cellular (Ig) enhancers share core sequences with viral enhancers and are species‑nonspecific.
• No teaching away. Generic statements that gene expression is "cell‑type dependent" or that myeloma cells are "specialised" do not amount to a clear teaching that the combination would not work (In re Fulton; In re Gurley — unpredictability is not teaching away).

6. Anticipated patentee rebuttals, and the weaknesses in the case

• § 103 burden. In litigation the challenger must prove obviousness by clear and convincing evidence; the examiner allowed these claims after amendment from the broad "transformed myeloma cell‑line" first aspect. The narrowing to three cell lines × three promoters plus a numeric output floor bears the hallmarks of art‑driven amendment and would be the focus of any validity challenge.
• Timing pitfalls (§ 102). Three items on the citation list appear to post‑date the 1985‑04‑01 priority date and should not be relied on: EP 0255320 A2 (Genzyme, priority 1986‑07‑28), the Catalogue of Cell Lines and Hybridomas, 6th ed. (1988), and Serfling et al., Trends in Genetics (Aug. 1985). Kudo et al., Gene 33:181‑189 (Feb. 1985) is only barely before the critical date. Also note the § 102(e) nuances: for a US patent to be a § 102(e) reference against a claim entitled to foreign priority, pre‑AIA law (In re Hilmer) limits the challenger's ability to use the § 119 date to reach back — an issue that would need to be briefed reference by reference.
• Citation artifacts. The page lists Shulman et al. as "Nature vol. 276, pp. 269‑270, Nov. 16, 1976," while the same page's specification cites "Shulman et al, 1978." I have not auto‑corrected this; the discrepancy should be resolved against the physical reference before relying on it. The specification also contains internal inconsistencies (e.g., "pAC1/pAC3" vs. the pAC1/pAC2/pAC5/pAC6 set; "P3.16"/"p3.16"; "pPRI/pPR1/pRI"), which complicate exact correspondence between the claims and the described plasmids.

7. Bottom line

Claim 1 would likely be held obvious as a combination of (i) a known myeloma host line — EP 0043718 A2 / US 4,472,500 (YB2/3.0.Ag.20), Shulman (SP2/O‑Ag14), Köhler/NSO — with (ii) a known, broadly functional strong viral promoter — Gorman et al. 1982 (RSV LTR), Perkins et al. 1983 / Hoffmann et al. 1982 (MoMLV LTR), or the pSV2/SV40 promoter cassette (SV40 late) — and (iii) routine selection/expression technology (Mulligan & Berg 1980, 1981; Southern & Berg; Maniatis 1982), with US 4,663,281 and US 4,740,461 / US 4,775,624 supplying express motivation to put a heterologous product gene under a strong promoter in a cultured myeloma line. The motivation was a recognized commercial need for high‑yield mammalian production of cloned secreted proteins; the field presented a finite, identified set of predictable solutions; and the specification's own data show the result was reached by routine ranking of those solutions. Claims 2–10 add only individual species of the same two variables. The "greater than 1 mg/L" limitation recites an inherent, result‑effective output of those same steps and, being unmet by the specification's own example for at least one claimed combination (claim 9 / p6gpt, 6.6 U/ml), is unlikely to supply the inventive weight the claim needs.

Confidence: moderate‑to‑high on the substance of the combinations for claims 1–4 and 8–10; moderate for claims 5–7 (MoMLV) and for the exact § 102(e) reach‑back dates, both of which require reference‑by‑reference verification against the physical documents.