US 5569825

I'll search for this specific patent number across patent and litigation sources.

Good — I have claim text from the RPX litigation database. Let me check for litigation/docket activity and verify the claim set.

Let me check the litigation history and any PTAB/CAFC proceedings specifically for this patent.

US 5,569,825 — Verified Summary

Confidence note up front: I was able to confirm bibliographic data and much of the disclosure from the Google Patents full text (which you supplied) plus the RPX litigation database. I could not retrieve an authoritative USPTO-hosted full claim set in this session, and I found no 2026 CAFC docket activity for this patent. Details on those limitations are flagged below rather than filled in.

Bibliographic data

Source: https://patents.google.com/patent/US5569825/en ; https://litigation.rpxcorp.com/patent/[US5569825A](/patent/US5569825A)

The filing is a later application in the Genpharm/Lonberg–Kay human-Ig transgenic-mouse family; the specification expressly cross-references the parent application "Transgenic Non-Human Animals Capable of Producing Heterologous Antibodies," U.S. Ser. No. 07/574,748, filed Aug. 29, 1990, and the correlating PCT filing PCT/US1992/010983 (published as WO 93/12227 on June 24, 1993).

Abstract (as published)

The invention relates to transgenic non-human animals capable of producing heterologous antibodies of multiple isotypes. Heterologous antibodies are encoded by immunoglobulin heavy chain genes not normally found in the genome of that species of non-human animal. In one aspect of the invention, one or more transgenes containing sequences that permit isotype switching of encoded unrearranged heterologous human immunoglobulin heavy chains are introduced into a non-human animal thereby forming a transgenic animal capable of producing antibodies of various isotypes encoded by human immunoglobulin genes. Such heterologous human antibodies are produced in B-cells which are thereafter immortalized, e.g., by fusing with an immortalizing cell line such as a myeloma or by manipulating such B-cells by other techniques to perpetuate a cell line capable of producing a monoclonal heterologous antibody. The invention also relates to heavy and light chain immunoglobulin transgenes for making such transgenic non-human animals as well as methods and vectors for disrupting endogenous immunoglobulin loci in the transgenic animal.

Plain-language overview of the independent claims

The RPX litigation record lists three independent claims (1, 7, 8) out of 8 total:

Claim 1 — The "isotype-switching minilocus" mouse (genus claim).
A transgenic mouse whose genome carries a heritable (germline) copy of an unrearranged human heavy-chain immunoglobulin minilocus transgene. The minilocus must contain, in operable arrangement:

• multiple human VH segments, multiple human D segments, and multiple human JH segments;
• an immunoglobulin heavy-chain enhancer;
• a mu (μ) constant region with its mu switch region upstream;
• a gamma (γ) constant region with a human gamma constant gene segment and a gamma switch region upstream.

Functionally, the mouse's B lymphocytes must perform V-D-J joining to produce an in-frame V-D-J gene that is expressed in polypeptide linkage to the human gamma constant region by isotype switching within the transgene ("intratransgene isotype switching"). Structurally, the minilocus must have at least one discontinuity of at least 2 kb between the mu and gamma segments relative to the natural human germline heavy-chain locus — i.e., it is a deliberately compacted/deleted construct, not a native locus. The mouse must express human IgM heavy chains and, as a result of isotype switching, human IgG heavy chains.

In plain terms: this is the core "HuMab-Mouse" concept — a mouse engineered with a compacted human IgH mini-locus that can rearrange human V/D/J segments and class-switch from IgM to IgG inside the animal.

Claim 7 — The pHC1-construct mouse (product-by-construct identity).
A transgenic mouse having an intact integrated germline copy of a human heavy-chain transgene having the NotI insert of pHC1, where the mouse expresses human mu and human gamma-1 immunoglobulin chains in its serum. This claim is anchored to a specific, structurally defined DNA insert rather than to functional language. pHC1 is the heavy-chain minilocus construct described in Example 12 of the specification (the patent text states the preferred embodiment uses "the transgene described in Example 12 (e.g., pHC1 or pHC2)").

Claim 8 — The pHC1 mouse producing fully human-sequence γ1 antibodies.
A transgenic mouse comprising an intact integrated germline copy of the NotI insert of pHC1, expressing in serum antibodies having human-sequence gamma-1 chains, where each such γ1 chain has a variable region whose polypeptide sequence is encoded by a human VH, human D, and human JH segment joined in-frame as a VDJ gene. This is the narrower, "human-sequence antibody produced in a mouse" claim.

Broader disclosure context (not necessarily claimed)

The specification describes a much broader platform than the three issued independent claims capture, including: unrearranged heavy and light chain miniloci; combinations of rearranged light chain with unrearranged heavy chain transgenes; immortalized B-cells/hybridomas secreting human-sequence monoclonal antibodies; methods of inducing isotype switching (e.g., IL-4, IFN-γ); methods of detecting isotype switching by Southern blotting/PCR/genomic cloning; positive–negative selection vectors for disrupting endogenous mouse heavy- and light-chain loci; donor/acceptor switch-region substitution to alter switching frequency; and a cloning method using unique XhoI/SalI sites flanked by NotI sites for ordered concatemerization of large fragments.

Litigation / CAFC check — results and gaps

• CAFC 2026 dockets: I found no Federal Circuit or district court activity in 2026 involving US 5,569,825. Searches returned only unrelated 2026 patent news (the Taction Technology v. Apple haptic verdict on U.S. Pat. Nos. 10,659,885 and 10,820,117), which does not involve this patent number.
• This is consistent with the patent's status: Expired – Lifetime, anticipated expiration 2013-10-29. A lapsed patent can still be asserted for past damages within the statutory lookback period, so absence of 2026 activity is an observation, not a legal conclusion.
• Caveat on claim text: The claim language above is taken from the RPX litigation database entry (https://litigation.rpxcorp.com/patent/US5569825A), which lists 8 claims and reproduces claims 1, 7, and 8. I could not in this session independently confirm the wording of dependent claims 2–6, nor verify whether any reexamination certificate, reissue, or certificate of correction altered the claim set after the 1996-10-29 grant. The Google Patents full text supplied to me contains the description but terminates before the claims section, so it does not independently corroborate the RPX claim text.
• Assignee lineage: Google Patents lists Genpharm International Inc as both original and current assignee. Genpharm's human-Ig transgenic mouse program was later associated with Medarex and Bristol-Myers Squibb; I did not verify the chain of title from an authoritative assignment record in this session, so treat any post-Genpharm ownership statement as unconfirmed.
• Family: Commonly cited sibling patents issuing from the same Lonberg/Kay program include US 5,545,806; 5,625,126; 5,633,425; 5,789,650; 5,877,397; 5,661,016; 5,814,318; 5,874,299; and 5,770,429. These are separate patent numbers — I have not conflated them with 5,569,825.

I'll research litigation involving US Patent 5,569,825. Let me run several targeted searches.

Let me refine my searches targeting litigation databases and the specific patent.

Let me dig into the specific case details.

I've gathered the available evidence. Note that I could not query PACER or the Unified Patents litigation portal directly — I hit my search-step limit and relied on public web results (docket aggregators, BioWorld/Sage "BLR" reporting, and SEC filings). Here is what I can document about litigation involving US Patent 5,569,825 ("Transgenic non-human animals capable of producing heterologous antibodies of various isotypes," Lonberg & Kay, issued 1996‑10‑29, original assignee GenPharm International Inc.).

Litigation involving US 5,569,825

Detail on Case 1 — GenPharm Int'l, Inc. v. Abgenix, Inc.

• Docket: Plainsite lists GenPharm Intl Inc v. Abgenix Inc., Cal. N.D., Civil No. 4:96-cv-03861, Judge Claudia Wilken presiding, with a related/consolidated case 4:97-cv-00058 and case 4:96-cv-00487. Docket activity includes an Abgenix motion for summary judgment (notice set for 4/18/97), an order relating the cases (entered 1/28/97), and a denial of a motion to dismiss the amended complaint. Source: https://www.plainsite.org/dockets/2y57i5ltc/california-northern-district-court/genpharm-intl-inc-v-abgenix-inc/
• Patents asserted: Reporting on the suit states GenPharm asserted two freshly issued patents — No. 5,545,806 ("methods of producing human antibodies using transgenic mice possessing human-antibody genes") and No. 5,569,825 ("the transgenic mice themselves"). Source: Biotechnology Law Report / Sage, "GenPharm Receives U.S. Patents for Mice Producing Human Antibodies; Sues Cell Genesys Subsidiary," 16 BLR 66 (1997), https://sage.cnpereading.com/paragraph/download/?doi=10.1089/blr.1997.16.66
• Outcome: The parties settled in March 1997. Under the agreement, Abgenix/Cell Genesys and Japan Tobacco entered into a worldwide, royalty-free cross-license covering issued and pending patents on generating fully human monoclonal antibodies in genetically modified mice. Cell Genesys issued GenPharm a $15 million note (convertible into ~1.67M shares of Cell Genesys common at $9/share); Japan Tobacco made an undisclosed cash payment and two potential $7.5 million milestone payments to GenPharm were contemplated. Sources: BioWorld, "Cell Genesys, GenPharm International Settle Legal Dispute, Form Partnership," https://www.bioworld.com/articles/[485617](/patent/485617) and the BLR article above.

Detail on Case 2 — Cell Genesys, Inc. v. GenPharm International, Inc.

This earlier action alleged misappropriation of trade secrets relating to transgenic antibody mice (filed ~February 1994, per BioWorld coverage of Feb. 2–3, 1994). It was dropped January 1997 and folded into the March 1997 global settlement/cross-license. It is relevant context but was not an infringement action on the '825 patent.

Related agreements / SEC-documented patent-rights activity

SEC filings reflecting the GenPharm cross-license (e.g., the Abgenix-related filing listing "GenPharm Cross License" and GenPharm application Ser. No. 07/574,748, Kay & Lonberg) corroborate that the '825 family was part of a broad patent cross-license rather than ongoing litigation: https://www.sec.gov/files/18-02711-e.pdf

Important caveats

• Confidence level: I am highly confident that GenPharm's 1996/1997 infringement suit against Abgenix is the principal litigation involving the '825 patent, and that it settled via cross-license in March 1997. I am moderately confident on the precise filing date and on exactly which patents/claims were asserted in the original complaint versus an amended complaint (the docket shows the complaint was amended).
• I could not confirm any other district-court or ITC action expressly asserting US 5,569,825 — no later Medarex-era or post-acquisition suits were identified in my search results. I did not return results for similar but different patent numbers (e.g., 5,545,806, 5,625,126, 5,633,425, 5,661,016, 5,545,807), which belong to the same family/families but are distinct patents.
• I was unable to retrieve the exact PACER filing date or the final dismissal order directly; if you need those, the definitive sources would be PACER for N.D. Cal. case 4:96-cv-03861 (and the related 4:97-cv-00058), or the Unified Patents litigation portal. I'd recommend verifying the filing date and the specific asserted claims there, since my answer relies on secondary reporting for those details.

I'll start by verifying the structured ODP result against the public record, then hunt for any older or unindexed AIA proceedings.

The ODP block says no proceedings; let me try to falsify that with several targeted searches before concluding.

No PTAB hits so far. Let me check for ex parte reexamination, Federal Circuit activity, and the on-face term/ownership record to complete the picture.

Proceedings overview

There are zero AIA trial proceedings on file for US 5,569,825 — no IPR, no PGR, no CBM, no derivation proceeding — so there is no PTAB outcome, no canceled claim, and no estoppel to hand a defendant; the patent's validity has never been tested at the Board, and the reason is almost certainly that it expired on 2013-10-29 and is now outside the § 286 damages lookback.

The structured ODP block in this prompt is the canonical list and it is empty ("no AIA trial proceedings for this patent as of the most recent ingest"). I attempted to falsify that with independent searching and could not. What I checked, and what I found:

No proceedings — supporting detail

• Type: n/a
• Filed: n/a
• Status: n/a — the canonical status is the patent's own: Expired - Lifetime, anticipated expiration 2013-10-29 (per the Google Patents record; this is the listed date and should be confirmed against Patent Center/EPAS, since it depends on term rules and any terminal disclaimer).
• Judge panel: none convened.
• Petition grounds: none filed.
• Institution decision: none.
• Final Written Decision: none.
• Settlement / termination: n/a as to PTAB. There was a district court case, and it matters contextually: GenPharm filed an infringement suit against Abgenix, Inc. (a Cell Genesys subsidiary) in October 1996 under US 5,545,806 and US 5,569,825, with a second suit under US 5,591,669; the dispute settled on 1997-03-27 in a cross-license under which GenPharm received up to $37.5M (reported elsewhere as ~$40M), and Cell Genesys withdrew its trade-secret suit on 1997-01-15. Sources: GenPharm corporate timeline (innovationtocashflows.com PDF) and contemporaneous coverage summarized in Biotechnology Law Report 16(1) ("GenPharm Receives U.S. Patents for Mice Producing Human Antibodies; Sues Cell Genesys Subsidiary," noting patent 5,569,825 "covers the transgenic mice themselves"). That settlement — not any Board ruling — is why no proceeding ever followed.
• Appeal: no Federal Circuit appeal of any PTAB decision exists (there is no decision to appeal). I did not locate a CAFC opinion in which the '825 patent was adjudicated on the merits.
• Defensive value: The absence of PTAB activity is not reassurance — it reflects commercial irrelevance, not patent strength. GenPharm was acquired by Medarex (1997), which was acquired by Bristol-Myers Squibb (2009), and the patent term ended in 2013. No one spent IPR money on an expiring research-tool patent.

⚠️ False-positive trap for docket searches. US 5,569,825 shows up constantly in PTAB records as prior art and as a bibliography entry, never as the challenged patent. Examples I hit: an exhibit list in IPR2017-01129 listing "Lonberg, N. and Kay, R.M., … U.S. Patent No. 5,569,825"; and IPR2024-00647 (Merck Sharp & Dohme v. Johns Hopkins), where Dr. Nils Lonberg's CV lists the '825 patent — that is the inventor appearing as a testifying expert, not a patent whose owner is defending a trial. Do not read those hits as proceedings on this patent.

Caveat on my negative findings. I searched until my tool budget ran out; I did not perform an exhaustive CourtListener RECAP sweep or a PTAB E2E "patent number" query, and I could not verify the claim set of '825 (the provided patent text contains the specification only, no claims), so I make no representation about which claims exist, are independent, or are dependent. Everything above is a statement about proceedings, which is what was asked.

Strategic summary

Claim status: everything is UNTESTED at the Board. Because no FWD issued, no claim of US 5,569,825 has been canceled, confirmed, or construed by the PTAB. There is no PTAB "surviving claims" list to give you. That is not the same as the patent being alive: the Google Patents record shows expiry on 2013-10-29, so the enforceable window closed over a decade ago. Any current demand letter asserting this patent must be premised on pre-expiration conduct, and 35 U.S.C. § 286 bars recovery for infringement more than six years before the complaint is filed — meaning a suit filed today can reach nothing. Practically, the patent's only remaining utility is as a licensing/portfolio citation (it is heavily cited by later antibody patents, e.g. in EP 1 813 672, US 10,056,945, US 10,072,069, US 7,455,535), not as an assertion vehicle.

Estoppel landscape: there is none, in either direction. § 315(e)(2) estoppel attaches only to a petitioner who was a party to an IPR that reached a final written decision, barring grounds it raised or reasonably could have raised. With no IPR, no petitioner is estopped, and the patent owner has obtained no validity finding that would carry preclusive or persuasive weight. For a defendant currently facing assertion, the entire universe of § 102/§ 103 art remains available in district court — there is no "reasonably could have raised" trap, no Board claim construction to work around, and no § 325(d) obstacle to the patent owner arguing that art was previously considered. The flip side: you also get no free kill. You cannot point to a canceled claim.

Pattern signals: no repeat petitioners, no serial challenges, no aggregator. No petitioner has filed multiple IPRs; no Unified Patents–style entity has challenged it; and the patent owner (the GenPharm line, now within Bristol-Myers Squibb via Medarex) has never had a PTAB appeal on this patent to prosecute. The only adversarial history is the 1996 GenPharm v. Abgenix litigation, resolved by cross-license in 1997 — a pattern of settlement and licensing, not Board warfare. AIA trials became available on 2012-09-16, giving roughly 13 months of overlap with the patent's remaining term (to 2013-10-29) plus the ability to file post-expiration; the industry declined to use it. That is a strong signal that the claims were either not worth attacking or not being asserted.

Recommended next steps

1. Confirm expiration before reading the demand letter seriously. Pull the Patent Center transaction history and any terminal disclaimer to verify the 2013-10-29 date, then check § 286. If the patent expired 2013-10-29 and the complaint was filed after 2019-10-29, the damages case is time-barred and the demand is worth little beyond a nuisance value. Start here: https://patents.google.com/patent/US5569825/en and USPTO Patent Center (https://patentcenter.uspto.gov).
2. Since no PTAB proceedings exist, there is no FWD to link or quote. Be explicit about that in any invalidity contentions or mediation statement — a plaintiff asserting this patent cannot claim "the claims have survived IPR," because they have never faced one.
3. Re-run the negative search yourself before relying on it. Use PTAB E2E / the PTAB "Patent Trial" search (https://ptacts.uspto.gov) with patent number 5569825, and CourtListener RECAP (https://www.courtlistener.com) for any 1996–1998 CAFC docket in the GenPharm/Abgenix dispute. My sweep was cut short; treat "no PTAB activity" as high confidence but not court-certified.
4. Do not confuse citation with challenge. If you or your team docket-hunt and hit the '825 number in IPR2017-01129 exhibit lists or IPR2024-00647 (Lonberg CV), that is prior-art/IDS and expert-CV noise. It is not a proceeding on this patent, and it creates no estoppel.
5. If the demand rests on live, unexpired family members (e.g. US 6,255,458, US 6,300,129, or later GenPharm/Medarex continuations), re-run this analysis on those numbers — this report covers only US 5,569,825.

I'll research the assignment record for US 5569825 across the specified sources.

Let me dig for the specific reel/frame records and the Medarex/BMS chain.

Let me try to surface the actual reel/frame entries and the litigation history.

Ownership & Assignment Reconstruction — US 5569825

Data-provenance caveat (read first). In this session I could not open USPTO Assignment Center (https://assignmentcenter.uspto.gov/) or the legacy assignment index (https://assignment.uspto.gov/patent/index.html) directly and read the underlying reel/frame pages. What I can confirm is the assignment event set as mirrored in the Google Patents legal-events pane for US 5569825 (https://patents.google.com/patent/US5569825/en), which is populated from USPTO assignment data. I therefore do not have verified reel/frame numbers for this patent and will not invent them. Where a reel/frame would normally appear below I say "not retrieved." Everything else is sourced to SEC filings, court/press coverage, and the patent's own front-matter data. Please re-run the Assignment Center query to fill the reel/frame cells.

Inventors

Notes on pattern:

• No "inventors depart within 12 months" flag. The application carries an Aug 29, 1990 priority date and was filed Dec 17, 1991; the inventors' assignment of interest was recorded Jan 27, 1992 — i.e., the inventors were still handing rights to the assignee at filing, the opposite of an abandonment pattern. Both inventors remained associated with the Genpharm program (Lonberg is widely reported as continuing with the acquired entity, Medarex, and later Bristol-Myers Squibb, and is a named inventor on the downstream anti-CTLA-4 / anti-PD-1 families). Treat the post-1997 career continuity as reported, not as an assignment-record fact.
• The co-inventor pair also appears together on the sibling Genpharm patents in the same family (e.g. US 5,545,806; US 5,629,425; US 5,661,016; US 5,814,318) — a single research team, not a stitched-together portfolio.

Original assignee

Genpharm International, Inc. — named as assignee on the face of US 5569825 and still shown as the current assignee of record in Google Patents' assignee field.

• Products embodying the claims: Yes — substantively. This is a life-sciences platform company, not a paper holder. Genpharm commercialized the HuMAb-Mouse™ line of transgenic mice (the claims of '825 are directed to the transgenic non-human animal itself, with the method claims in sibling '806). Genpharm sold/licensed transgenic mice and antibody-discovery services, and entered collaborations with Eisai, Centocor and LeukoSite, per the company's own profile and 1997 deal coverage.
• Primary line of business: transgenic animal technology for fully human monoclonal antibody discovery — a biotech R&D/platform business, later described as the antibody-discovery arm of Medarex's UltiMAb platform.
• Litigation posture while owner: Genpharm was an asserting operating company, not an NPE. In October/November 1996 — within days of the Oct 29, 1996 issuance of '825 and '806 — Genpharm sued Abgenix, Inc., a wholly-owned subsidiary of Cell Genesys, Inc., under both patents, alleging infringement by the competing XenoMouse program (BioWorld / Biotechnology Law Report coverage; Stanford GSB case IB38). That dispute was resolved by a March 26, 1997 settlement and cross-license among Cell Genesys, Abgenix, Xenotech L.P., Japan Tobacco and Genpharm International (document listed in Medarex's SEC exhibit index).
• Current status: Genpharm International, Inc. ceased to be independent in 1997, when Medarex, Inc. acquired it in a stock transaction valued at up to ~$65 million (announced Feb/May 1997; completed October 1997). Medarex was itself acquired by Bristol-Myers Squibb for $2.4 billion, announced July 22, 2009 and closed in 2009. SEC filings as late as the Nov 2004 PharmAthene collaboration agreement still refer to "Medarex, Inc., on behalf of itself and its wholly owned subsidiary, GENPHARM INTERNATIONAL, INC.," i.e. the Genpharm entity persisted as a wholly-owned subsidiary rather than being merged out. Status today: dormant/absorbed subsidiary within BMS; not an independent operating company. The patent itself expired Oct 29, 2013 (17-year term from the 1996 grant), so there is no live exclusivity.

Assignment timeline

Records retrievable for this patent are sparse. The only inventor→assignee record I can confirm from the mirrored legal-events data is the 1992 filing. There is no evidence in the mirrored data of any post-issuance recorded assignment from Genpharm International to Medarex or to Bristol-Myers Squibb — consistent with the patent simply staying parked in the name of the wholly-owned Genpharm subsidiary through both acquisitions. Reel/frame values below are marked "not retrieved" rather than guessed; verify at Assignment Center.

• 1992-01-27 (recorded; execution date not retrieved) — Reel not retrieved / Frame not retrieved

  • Conveyance: Assignment of assignors' interest (the entry reads "ASSIGNMENT OF ASSIGNORS INTEREST")
  • Assignor: Robert M. Kay and Nils Lonberg (joint inventors)
  • Assignee: Genpharm International (Genpharm International, Inc.)
  • Correspondent: not retrieved — the mirrored event data does not expose the recording correspondent, and I found no secondary source naming it. Do not infer a firm from the assignee's counsel; the recording correspondent is a distinct data field.
  • Context: Sweat-equity/employment assignment — inventors conveying rights to their employer at/around filing; the originating link in the chain.

• 1997 (completed October 1997; announced Feb and May 1997) — no recorded assignment found on the patent

  • Conveyance: corporate acquisition (stock-for-stock merger / purchase) of Genpharm International, Inc. by Medarex, Inc., up to ~$65M
  • Assignor: Genpharm International, Inc. (target) — Assignee (parent): Medarex, Inc.
  • Correspondent: not retrieved / not applicable — this is an M&A event surfaced in SEC filings and press, not a USPTO-recorded patent assignment I could verify. Because Genpharm survived as a wholly-owned Medarex subsidiary, the patent likely never needed assigning.
  • Context: acquisition of an operating company (not a portfolio spin-out).

• 2009 (announced 2009-07-22; closed 2009) — no recorded assignment found on the patent

  • Conveyance: corporate acquisition of Medarex, Inc. by Bristol-Myers Squibb for $16.00/share, ~$2.4B
  • Assignor: Medarex, Inc. (and its Genpharm subsidiary) — Assignee (parent): Bristol-Myers Squibb / E. R. Squibb & Sons, L.L.C. family of entities
  • Correspondent: not retrieved / not applicable — M&A event, not a verified USPTO patent recording for this number.
  • Context: large-pharma acquisition of an operating antibody company; portfolio remained inside the acquired corporate family.

• No other assignment, security interest, license, release, merger, or change-of-name records identified for US 5569825.

If Assignment Center in fact shows a Genpharm→Medarex recorded assignment (some M&A deals do paper the IP over at closing), that link exists and I simply could not see it — flag it as "corporate reorg, recording expected at deal close." Conversely, if Assignment Center shows only the 1992-01-27 entry, that confirms the subsidiary-parking structure described above.

Timeline diagram

timeline
    title Ownership of US 5569825
    1990 : Priority application filed Aug 29
    1991 : Application filed Dec 17
    1992 : Inventors assign to Genpharm
    1996 : Patent issued Oct 29
         : GenPharm sues Abgenix
    1997 : GenPharm acquired by Medarex
         : Cross license ends Abgenix suit
    2009 : BMS acquires Medarex
    2013 : Patent expires Oct 29

NPE / troll-pattern signals

1. Shell-entity transfer — not present. The only recorded conveyance is the 1992-01-27 inventor→Genpharm International assignment. The assignee is an operating biotech with collaboration agreements, SBIR participation and a named commercial platform (HuMAb-Mouse), not a licensing LLC. No "IP / Holdings / Ventures" successor appears at any point; the downstream changes (Medarex 1997, BMS 2009) are corporate acquisitions, not transfers to single-purpose vehicles.

2. Known asserter in the chain — not present. Genpharm International, Medarex, Inc. and Bristol-Myers Squibb appear on none of the canonical NPE rosters (Acacia, Marathon, Intellectual Ventures, IPNav, Wi-LAN, Mosaid/Conversant, Vringo, Pendrell, Innovatio, MPHJ, Lumen View, Round Rock, Document Generation Corp, Spangenberg entities). The counterparty Genpharm sued in 1996 — Abgenix/Cell Genesys — was itself an operating antibody company. This is operating-company-vs-operating-company assertion.

3. Repeat correspondent across the chain — unclear / not retrievable. The correspondence-of-record field was not exposed by the mirrored legal-events data I could access, and no secondary source names the recording attorney for the 1992-01-27 entry. I found no recurrence pattern to report. This must be resolved by pulling the reel/frame images in Assignment Center — it is the single highest-value missing data point in this analysis, because a repeat correspondent is the tell that would convert an apparently clean chain into an arranged one.

4. Cascading transfers — not present. One recorded transfer across a 23-year life, followed by two corporate M&A events within the same corporate family (1997, 2009). No chained LLCs, no shared registered-agent addresses observed, no sub-24-month serial conveyances.

5. Pre-litigation transfer — not present. The 1996 assertion against Abgenix was brought by the entity that had owned the patent since 1992 and had developed the claimed mice itself. No assignment was recorded in the six months before the suit; there was no need to "clean up standing" because standing was never in question.

6. Bankruptcy fire-sale — not present. Genpharm's cancelled 1994 IPO (caused by a competitor's trade-secret suit) and its 1997 sale to Medarex were not proceedings under the Bankruptcy Code; the March 1997 resolution was a private settlement and cross-license, and the sale was an arm's-length merger. No Chapter 7/11, no court-supervised IP sale.

7. Privateering — not present. No operating company transferred these claims to an NPE to assert against competitors on its behalf. BMS acquired Medarex outright and kept the portfolio in-house; the patents expired in 2013 without a surrogate litigant appearing.

8. Defensive aggregator — not present. The chain does not terminate at RPX, AST, LOT Network, Unified Patents or OIN. The terminal rights-holding entity is a BMS subsidiary (Genpharm International, Inc., still of record as assignee), not a defensive aggregator — so the patent was not neutralized by defensive purchase; it simply expired.

Verdict

Operating-company assertion.

Justification: the only recorded conveyance on US 5569825 is the 1992-01-27 assignment of the inventors' interest to Genpharm International, Inc., an operating transgenic-antibody company whose HuMAb-Mouse product embodied the claims, and the only assertion event in the patent's life was Genpharm's own 1996 infringement suit against Abgenix / Cell Genesys under '825 and its sibling '806 — an operating-company-versus-operating-company dispute, not an NPE campaign. The subsequent ownership changes are two ordinary corporate acquisitions (Genpharm→Medarex 1997, ~$65M; Medarex→Bristol-Myers Squibb 2009, $2.4B) with no recorded assignment to any licensing LLC and no reeling of this patent into an asserting vehicle, and the patent expired 2013-10-29, ending all assertion exposure. Residual uncertainty is confined to the missing reel/frame and correspondent fields: if Assignment Center shows a correspondent recurring across a Genpharm→Medarex→BMS papering chain, that is normal in-house/corporate M&A recording and would not change the verdict, but it should be captured for completeness.

Verify and back-fill the reel/frame and correspondent cells here:

• USPTO Assignment Center: https://assignmentcenter.uspto.gov/ (search patent number 5569825)
• Legacy assignment index: https://assignment.uspto.gov/patent/index.html
• Legal-events mirror used above: https://patents.google.com/patent/US5569825/en

I'll research this patent's citation record and prior art. Let me start with searches.

Let me get the specific citation list from the patent's Google Patents page.

Let me try to retrieve the front-page references-cited list from other patent databases.

Prior-Art Analysis — US 5,569,825

Important sourcing caveat (read first). I was able to confirm the patent's bibliographic data, its family, and its specification's own reference list from primary/secondary sources, but I could not directly retrieve the printed front-page "References Cited — U.S. Patent Documents" table for US 5,569,825 from the sources reached in this session. The closest verified equivalents I have are (a) the non-patent and patent references cited in the specification itself (retrieved from the patent text), and (b) the search-report citations for the sibling EP application in the same family (EP 0814159 / WO 92/03918, GenPharm, same Aug. 29 1990 priority), which is the standard proxy for the cited art in this family. Where I state "cited on the front page," treat it as unverified for the U.S. front page; where I state "cited in the specification" or "cited in the family search report," that is grounded. I have not fabricated claim numbers; the claim set was not present in the fetched text, so claim mapping is given by claim subject matter.

Key bibliographic facts (verified, Google Patents):

• US 5,569,825 A — "Transgenic non-human animals capable of producing heterologous antibodies of various isotypes"
• App. No. US 07/810,279; filed 1991-12-17; priority 1990-08-29; granted 1996-10-29; assignee Genpharm International, Inc.; inventors Nils Lonberg and Robert M. Kay; expired (anticipated expiration 2013-10-29). Source: https://patents.google.com/patent/US5569825/en

A. Patent documents — prior art

Note on the search hit listing "Patent Citations (11)" with US 5,023,179 / US 5,110,732 / US 5,276, etc.: that table belongs to US 6,927,320 (a plant patent) which merely cites US 5,569,825 — it is not the reference list of US 5,569,825 and must not be conflated with it.

B. Non-patent literature — prior art (cited in the specification and/or the family search report)

C. Bottom line

1. Most relevant single prior-art reference: Durdik et al., PNAS 86:2346–2350 (April 1989) — it discloses isotype switching of a microinjected μ heavy-chain gene in transgenic mice and is expressly cited as applicant art ("[DA]"). It is the strongest §102/§103 reference against the case's core claims directed to a heterologous heavy-chain transgene with two or more C_H genes and functional switch sequences that undergoes isotype switching.

2. Supporting prior art for the switching construct: Nikaido (1981, 1982) (Sμ structure), Ott et al., EMBO J. 6:577–584 (1987) (switch recombination in a vector in pre-B cells), and Yasui et al. (1989) (δ-associated repeats) map onto claims reciting switch donor/acceptor sequences and non-classical switching.

3. Antibody-production-in-transgenic-animals art: WO 90/04036 (MRC) and Bruggemann et al. (1989), with Nussenzweig et al. (1988) for B-cell maturation/allelic exclusion, map onto the claims directed to the transgenic animal and its human-antibody repertoire.

4. These references generally support §103 (obviousness) rather than naked §102 anticipation. Individually, none of the retrieved references discloses the full combination recited (an unrearranged human heavy-chain minilocus with ≥2 C_H genes, functional switch regions, and demonstrated in vivo isotype switching to produce heterologous IgG/IgA/IgE). The Durdik art comes closest to §102 on the "isotype switching" concept but does not appear to disclose the full transgene architecture of the claims.

5. Verification gap to flag: the exact U.S. front-page "References Cited" table for US 5,569,825 was not recoverable in this session. To make the §102/§103 mapping claim-number-specific and airtight, the printed front page (or the USPTO PatentCenter/IFW file) should be pulled directly, and the actual claim set of US 5,569,825 obtained (it was not part of the text I reviewed). I recommend that verification before relying on any anticipation conclusion.

I'll ground this analysis in the actual claim language and cited art rather than memory, so let me pull a couple of authoritative sources first.

I have the operative claim language. Let me now probe the prior-art of record and the contemporaneous art on isotype switching, since the fetched page text preserved only in-text citations.

Strong material. Two more targeted checks — the substantive teaching of the key switching reference, and the remaining claims.

Obviousness Analysis — US 5,569,825 (Lonberg & Kay, Genpharm; filed 17‑Dec‑1991; priority 29‑Aug‑1990; expired 29‑Oct‑2013)

0. What I verified, and what I could not

Source page: https://patents.google.com/patent/US5569825/en

1. The claim at issue (claim 1, verbatim from the mirror)

"A transgenic mouse having a genome comprising a germline copy of an unrearranged human heavy chain immunoglobulin minilocus transgene comprising a plurality of human V_H gene segments, a plurality of human D gene segments, a plurality of human J_H gene segments, an immunoglobulin heavy chain enhancer, a mu constant region comprised of a mu switch region located upstream from a mu constant gene segment, a gamma constant region comprised of a gamma switch region located upstream from a human gamma constant gene segment, and wherein B lymphocytes of said transgenic mouse rearrange said unrearranged human heavy chain transgene by V‑D‑J joining to produce a V‑D‑J gene joined in‑frame encoding a heavy chain variable region expressed in polypeptide linkage to the constant region encoded by said human gamma constant gene segment on said transgene by intratransgene isotype switching, and wherein said minilocus transgene has at least one discontinuity of at least 2 kb between said mu and gamma gene segments as compared to a human germline heavy chain locus, wherein said mouse expresses human IgM heavy chains, and as a result of isotype switching, human IgG heavy chains."

Claims 7–8 are product‑by‑construct claims to a mouse with "an intact integrated germline copy of a NotI insert of pHC1" expressing human μ and human γ1 chains.

Two construction points drive the whole analysis: claim 1 is silent on (a) knockout of the endogenous mouse IgH locus and (b) any light‑chain transgene. That makes claim 1 almost exactly the Brüggemann mouse plus a downstream human Cγ. The only genuinely load‑bearing limitation is "intratransgene isotype switching."

2. Prior art available against the 29‑Aug‑1990 priority date (pre‑AIA § 102)

Date trap to flag: Gerstein et al., Cell 63:537‑548 (1990) (https://www.informatics.jax.org/reference/allele/MGI:[4442646](/patent/4442646)) — "Isotype switching of an immunoglobulin heavy chain transgene occurs by DNA recombination between different chromosomes" — is the single most on‑point reference (it proves transgene switch recombination uses the same enzymatic mechanism as normal switching), but it was published ~Nov. 1990, after the 29‑Aug‑1990 priority date. It and Bruggemann 1991 (Eur. J. Immunol. 21:1323), Taylor 1992, and Tuaillon 1993 are available only against new matter added in the 17‑Dec‑1991 CIP or later. If prosecution relied on any of these, that is a priority/§ 112 written‑description vulnerability worth probing separately.

3. Element mapping of claim 1

4. Grounds of rejection

Ground 1 (strongest): Bruggemann 1989 in view of Durdik 1989, further in view of Nikaido 1981/1982 and Mowatt 1986.
Motivation: Bruggemann expressly framed the minilocus as a way to make a human antibody repertoire, and delivered only human IgM. The stated therapeutic goal — human IgG for therapy — is frustrated by an IgM‑only animal, a problem the '825 Background itself acknowledges ("Transgenic animals that cannot switch isotypes are limited to producing heterologous antibodies of a single isotype… such as IgM and possibly IgD, which may be of limited therapeutic utility"). Reasonably expected to work: Durdik proved a randomly integrated Ig transgene can undergo an isotype switch producing IgG (four independent founder lines), and Nikaido/Mowatt establish that switching is recombination between S regions positioned immediately 5' of each C_H gene, with Cμ deleted. Since the classical mechanism is intramolecular (cis) deletion, a PHOSITA linking a human Sγ/Cγ cassette downstream of Cμ in the same construct would expect cis switching — the same prediction that was later confirmed. The KSR rationales apply cleanly: a known problem, a finite set of known C_H options (γ1–γ4, α1–α2, ε), the patent's own statement that γ1 and γ3 are the preferred choices, and a predictable arrangement copied from the germline locus.

Ground 2: Ground 1 + Bruggemann 1991 (or Berman 1988) for "a plurality of human V_H." Needed only if the examiner reads Bruggemann 1989's single human V_H as failing "plurality"; the 100 kb IgH transgene supplies it, at the cost of the priority‑date problem noted above.

Ground 3: Ground 1 + Berton 1989 / Esser & Radbruch 1989 / Coffman 1986, 1987. These supply the recited "gamma switch region located upstream from a human gamma constant gene segment" plus its functional 5' flank. The '825 specification itself concedes that human and mouse S regions are "very similar," and that switching frequency is governed by the 5' flanking/sterile‑transcript elements — so grafting the Sγ1 flank to a human Cγ is the ordinary design step the art already described. This ground is what makes the claim's regulatory‑element language (and dependents reciting Sγ1/4 kb flanking sequences, if the USPTO‑reported claim text is confirmed) vulnerable.

Ground 4 (belt‑and‑suspenders): Ground 1 + Yasui 1989. Yasui teaches the 400 bp δ‑flanking direct repeats as an alternative, non‑classical switching route — evidence that the art already viewed "provide the recombination substrate in cis in the transgene" as the operative teaching, supporting the motivation element.

Ground 5 (claims 7–8, pHC1): Ground 1 + Petterson 1990 (rat IgH 3' enhancer, Nature 344:165‑168) + the plasmid's public availability. Claims 7–8 add no element beyond (i) the pHC1 construct, (ii) serum human μ and γ1. If the pHC1 plasmid was publicly available (e.g., an ATCC deposit), making the mouse is a mechanical application of Ground 1 to a known article of commerce. I could not verify a deposit — this is a documentary gap that materially changes the outcome, because these two claims are the only ones with a plausible non‑obviousness defense.

5. The patentee's counter‑arguments, and how they fare

1. "No reference taught intratransgene switching." Durdik's switching was interchromosomal trans-switching (four founders, transgene unlinked to Igh). Genuine gap. But it cuts both ways: Durdik expressly concluded that "a precise chromosomal location is not required for isotype switching" and that integration site does not matter — which removes the principal doubt a PHOSITA would have had about a randomly integrating construct. The classical cis mechanism (Nikaido) supplied the expectation.
2. Unexpected results. The Background asserts "there have been no reports of heterologous transgenes that undergo successful isotype switching." Strong rhetoric, weak as § 103 rebuttal: the asserted unexpected result (a human Sμ→Sγ1 switch functioning in mouse) is not commensurate with claim 1's scope (all miniloci meeting the structural limitations, with no light chain and no knockout required). Under Leo Pharmaceutical v. Rea, unexpected results must be coextensive with the claim.
3. Failure of others / long‑felt need. Bruggemann 1989 and Bruggemann 1991 are both IgM‑only; the need for human IgG was acknowledged for years. This is the patentee's best secondary‑considerations evidence, and it is usable. Note, however, that a "recognized problem, unsolved" showing cuts for motivation as much as for non‑obviousness.
4. Teaching away. Weak. The closest candidate is the field's interest in very large loci/YACs (Berman 1988; Bruggemann 1991) to obtain repertoire size, which could be argued to direct away from a 70–80 kb minilocus — but that goes to expression level, not to the recited switching capability.
5. Prosecution history estoppel/actual allowance. The examiner allowed claim 1 over this art, which is some (non‑binding) contemporaneous evidence of non‑obviousness.

6. Bottom line

• Claims 1 (and its dependents): the art combination of Bruggemann 1989 + Durdik 1989 + Nikaido/Mowatt maps every recited element, and the gap (linkage of a human Sγ/Cγ in cis with Cμ) is filled by the known cis‑deletion mechanism of class switching plus the trivial design incentive to obtain human IgG. I would rate this ground strong — perhaps 65–75% to prevail before an impartial tribunal on the current record, contingent on the priority‑date problem with Gerstein 1990 and on the untested functional‑limitation argument (no reference actually performed intra‑transgene switching before the priority date; that is a real, if narrow, point for the patentee).
• Claims 7–8: survive or fall based almost entirely on whether pHC1 was publicly available. Unverifiable here — flag as the single most important documentary gap.
• Sequencing note: the cleanest petitioner's ground would run Bruggemann 1989 (102(a)) as primary, Durdik 1989 (102(b)) as the switching teaching, Nikaido 1981/Mowatt 1986 for the switch‑region architecture, and Berton 1989/Esser & Radbruch 1989/Coffman 1986 only if the claims are read to require the γ 5' flank. Gerstein 1990 should be pleaded in the alternative with an explicit § 102(e)/CIP‑priority chart.