US 5633425

I'll search for the specific patent number to ground this summary.

Let me try to retrieve the actual claim language.

Let me try to pin down the full claim set.

Summary — US 5,633,425

Confidence note up front: The bibliographic data below is corroborated by multiple independent sources (Google Patents full text supplied to me, RPX/insight.rpxcorp, uspto.report, Unified Patents, FreePatentsOnline). The full text of the patent I was given is truncated in the middle of the Examples and does not include the claims section, so I could verify independent claim 1 only via a secondary source (RPX). I could not authoritatively verify the total claim count or whether there are additional independent claims. I flag that specifically rather than guessing.

Bibliographic data

Discrepancy flagged: Google Patents and the patent text list the priority date as 1990-08-29; Unified Patents' record lists 1990-08-28. These likely differ only by time zone indexing convention. I use 1990-08-29, matching the authoritative patent record.

Abstract (verbatim from the record)

"The invention relates to transgenic non-human animals capable of producing heterologous antibodies, i.e., antibodies encoded by immunoglobulin heavy and light chain genes not normally found in the genome of that species of non-human animal. In one aspect of the invention, transgenes encoding unrearranged heterologous human immunoglobulin heavy and light chains are introduced into a non-human animal thereby forming a transgenic animal capable of producing antibodies 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… 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. The invention also includes methods to generate a synthetic immunoglobulin variable region gene segment repertoire used in transgene construction and methods to induce heterologous antibody production…"

Plain-language overview of independent claim 1

Claim 1 (as retrieved from RPX's claim text for US 5,633,425 A) is directed to a transgenic mouse, and can be broken down as follows:

1. The animal and the genetic construct. A transgenic mouse whose germline DNA contains DNA segments from the human immunoglobulin heavy chain gene locus, assembled into a heavy chain "mini-locus" — i.e., a deliberately reduced/down-sized version of the human locus, not the full native locus.

2. The two-stage immune response the mouse must produce. Upon antigenic stimulation the mouse must develop:

   • Primary response B cells expressing IgM whose mu (μ) chain is encoded by a rearranged human mini-locus; and
   • Secondary response B cells expressing somatically mutated IgG whose gamma (γ) chain is encoded by the rearranged human mini-locus.

3. Composition of the unrearranged mini-locus. It must contain: a plurality of human heavy chain V gene segments, a plurality of human D segments, a plurality of human J segments; a μ constant region made up of a μ switch region located upstream of a μ coding segment; and a γ constant region made up of a γ switch region located upstream of a human γ coding segment.

4. Key structural limitation — compaction of the constant regions. The γ constant region must be in closer proximity to the μ constant region than it is in the natural human immunoglobulin heavy chain locus. In other words, the constant-region architecture of the human locus has been rearranged/compacted in the transgene to put μ and γ near each other.

5. Requirements on the primary response B cells. Their chromosomal DNA must contain both the μ constant region and the human γ constant region, plus a rearranged variable region produced by VDJ recombination of the mini-locus. The rearranged variable region must have N-region nucleotides at the V–D and D–J recombination joints, and the FR1, FR2, FR3, CDR1 and CDR2 portions of that variable region must derive from the human V segments of the mini-locus.

6. Requirements on the secondary response B cells. Their chromosomal DNA must show class-switch recombination from the μ constant region to the γ constant region, operably linked to the rearranged variable region — i.e., actual IgM→IgG switching at the DNA level.

7. Requirement evidencing somatic hypermutation. Finally, the sequence spanning FR1, FR2, FR3, CDR1 and CDR2 must include a plurality of DNA sequences that are not identical to the corresponding sequences in the unrearranged human mini-locus — i.e., the variable region has accumulated mutations relative to germline.

In short: Claim 1 covers a mouse carrying a human heavy-chain mini-locus that (a) undergoes genuine V(D)J rearrangement with junctional (N-region) diversity, (b) undergoes authentic IgM→IgG class switching, and (c) undergoes somatic hypermutation, where the μ and γ constant regions of the transgene are placed closer together than in the natural human locus.

Claim-set caveat

Given the truncated text, I cannot state with confidence how many total claims US 5,633,425 contains or whether there are independent claims beyond claim 1 (e.g., to transgene constructs, vectors, targeting methods, or to mice with light-chain transgenes). Earlier sections of this family's specification (supplied in the full text) describe many such aspects — unrearranged heavy and light chain transgenes, positive–negative selection vectors for disrupting endogenous Ig loci, synthetic V-segment repertoires, and immunization/"antibody sharpening" methods — but the presence of these as claims in this specific patent is not established from what I retrieved.

CAFC 2026 docket search — no results

A targeted search of the CAFC 2026 docket for this patent number returned no 2026 appellate docket activity. This is consistent with the patent's listed status (Expired – Lifetime; anticipated expiration 2014-05-27). The only 2026-dated materials surfacing in searches were unrelated third-party patents citing US 5,633,425 as background art (e.g., the "HuMAb-Mouse" references in antibody patent specifications). Note that the IPR materials that appeared in search results (IPR2020-00389) concern a different patent (a 2009-priority transgenic-mouse patent), not US 5,633,425 — I mention this only to avoid a false match.

Caveats on method: I searched Google Patents/patent aggregators rather than the USPTO PatentCenter or PACER/CAFC dockets directly, so this is not a substitute for an official litigation-status check. If you need a certified litigation posture, the USPTO PatentCenter and the Federal Circuit docket should be queried directly.

I'll research litigation involving US patent 5633425. Let me search multiple sources.

Let me search more targeted sources for litigation records.

Litigation Search Report — U.S. Patent No. 5,633,425

Patent: U.S. 5,633,425 ("Transgenic non-human animals capable of producing heterologous antibodies")
Inventors: Nils Lonberg, Robert M. Kay
Assignee/owner of record: Genpharm International, Inc. (later Medarex; ultimately BMS)
Appl. No.: 07/834,539 | Filed: Feb. 5, 1992 | Priority: Aug. 29, 1990 | Granted: May 27, 1997 | Expired: May 27, 2014

Bottom line

I found no litigation — district court, ITC, or PTAB — in which U.S. Patent No. 5,633,425 is identified as an asserted, challenged, or otherwise involved patent. I am not able to report plaintiff, defendant, jurisdiction, case number, filing date, or outcome, because my searches surfaced no case naming this patent. I want to be explicit that this is a negative finding from limited searching, not a certified "clean" record.

Because the patent expired on May 27, 2014 (Google Patents, https://patents.google.com/patent/[US5633425](/patent/US5633425)/en, "Anticipated expiration 2014-05-27"; status "Expired - Lifetime"), any infringement suit would necessarily have been filed before that date, and even a declaratory-judgment or § 271(e)(1) action would be unusual today. That is consistent with the absence of current hits.

What I searched and what came back

Key limitation: I could not directly query PACER docket text, Docket Alarm's "Litigation" tab, or RPX Insight's case database with this patent number in a way that returned docket-level records. Those are the sources most likely to hold a pre-2014 assertion, so my negative result should be treated as incomplete rather than exhaustive.

Adjacent proceedings I could not verify for this patent (leads, not findings)

I want to flag these without asserting them as facts, since my searches did not confirm any of them and I will not manufacture case numbers:

1. USPTO interference activity in the transgenic-antibody field. The Lonberg/Kay Genpharm family — U.S. 5,545,806; 5,569,825; 5,625,126; 5,633,425; 5,661,016; 5,770,429; 5,789,650; 5,814,318; 5,874,299; 6,255,458 — is frequently discussed alongside competing "human antibody mouse" work (Abgenix/Cell Genesys/Kucherlapati "XenoMouse" line, e.g. U.S. 5,939,598; Regeneron "VelocImmune"). I have a general recollection that contested proceedings occurred in this technology space, but I could not confirm any interference naming the '425 patent, and interference is in any event a USPTO proceeding, not "litigation" in the sense you asked about (no plaintiff/defendant, no jurisdiction, no case number in the district-court sense).
2. European counterpart. EP 0 546 073 B1 appears in the same family (priority Aug. 29, 1990). EPO opposition proceedings against that counterpart are plausible and would have engaged Genpharm and opponents — but that is a proceeding on the EP patent, not on U.S. 5,633,425, and I did not verify it.
3. Post-issuance U.S. proceedings. I found no evidence of ex parte reexamination, IPR/PGR, or reissue involving the '425 patent. (Note: IPR would be unavailable today given the 2014 expiration and the statutory time bar for pre-AIA patents.)

If any of these leads matters to your matter, they must be confirmed against primary records before being relied on.

Recommended verification path (if you need a certifiable answer)

1. USPTO Patent Center / Patent Assignment Search for appl. 07/834,539 — assignment records there sometimes reveal litigation-related transfers (e.g., to a litigation vehicle).
2. Docket Alarm patent page "Litigation" tab (docketalarm.com) and RPX Insight (insight.rpxcorp.com) case list — these index district-court complaints by patent number back to the 1990s.
3. PACER / CourtListener RECAP full-text search on "5,633,425" and on the patent's title, not just the number.
4. Unified Patents litigation portal case list (https://portal.unifiedpatents.com/litigation/caselist) — search by patent owner "Genpharm," "Medarex," and "Bristol-Myers Squibb" as well as by patent number, since older complaints frequently identify patents by title.
5. CAFC docket search for appeals arising from any such case.
6. Confirm with Genpharm/Medarex successor (BMS) licensing litigation history, if available.

Caveats

• Per your instruction, I have interpreted "5633425" literally as U.S. Patent No. 5,633,425 and have not substituted any similar number; likewise I have not silently corrected any family-member numbers appearing in the sources above.
• My negative result is based on publicly indexed web results and one fetch of the Google Patents record. Absence of evidence here is not proof that no suit was ever filed, particularly for 1990s–2000s docket records that are poorly indexed.
• I have deliberately left blank every field I could not ground (plaintiff, defendant, jurisdiction, case number, filing date, status/outcome) rather than fill them by inference.

Proceedings overview

PTAB proceedings on file for US 5,633,425: zero. The canonical structured list supplied from the USPTO Open Data Portal (AIA trial proceedings) is empty, and independent web searching surfaced no IPR, PGR, CBM, or derivation proceeding naming this patent or its application number 07/834,539 — so the breakdown is 0 active / 0 claims-invalidated / 0 claims-sustained / 0 settled / 0 institution-denied. The bottom-line defensive posture is therefore not "hardened by surviving IPRs" and not "claims canceled" — it is that the patent is expired (anticipated expiration 2014-05-27, per the Google Patents bibliographic record), no AIA trial ever tested it, and there is consequently no PTAB estoppel record to work from and no live claim to attack. Any demand letter asserting 5,633,425 today is a paper tiger on remedies: term ended over a decade ago and the 35 U.S.C. § 286 six-year damages lookback closed in 2020.

No proceedings to enumerate

There is no {PROCEEDING_NUMBER} to report. Per the governing instruction — "the default should be 'no PTAB activity on file'" — that default is confirmed rather than rebutted.

What I checked and what I did not find:

• AIA trial proceedings (IPR/PGR/CBM/derivation). None in the structured ODP block; none surfaced in searches against the patent number, the title ("Transgenic non-human animals capable of producing heterologous antibodies"), or the inventors (Lonberg, Kay) combined with PTAB/IPR terms.
• Pre-AIA inter partes reexamination or ex parte reexamination. I found no evidence of either, but I cannot rule it out to a certainty from the sources available — reexamination certificates are not in the ODP AIA-trial data set. Flagging this as an unverified negative rather than a confirmed one; it would not change the defensive posture anyway (see below).
• Federal Circuit appeals. None traceable, because there is no PTAB FWD and no Board decision to appeal. No Appeal No. / CAFC docket number exists to cite.
• Collateral district-court history (context only). The GenPharm/Abgenix patent war of the mid-1990s was pleaded on US 5,545,806 and US 5,569,825 (Oct. 1996), and later US 5,591,669 (Jan. 1997), against Abgenix, Inc., a Cell Genesys subsidiary; Cell Genesys withdrew its own suit in January 1997 and the parties cross-licensed (Stanford GSB case IB38; Biotech Law Report 1997, "GenPharm Receives U.S. Patents for Mice Producing Human Antibodies; Sues Cell Genesys Subsidiary"). I found no source showing 5,633,425 itself was ever asserted in that campaign or any later one.

Practitioner warning — do not conflate the numbers. Searching "425" against PTAB dockets overwhelmingly returns US 7,821,425 ("Capacitive keyboard with non-locking reduced keying ambiguity"), asserted by Advanced Integrated Circuit Process LLC against TSMC and UMC in E.D. Tex. and challenged in IPRs such as IPR2025-00372-adjacent filings. That is a completely unrelated patent owned by a different party. Any clearance or invalidity search run on "425" without the full 5,633,425 string will produce false hits.

Strategic summary

Claim status: UNTESTED, then EXPIRED. No claim of 5,633,425 was ever canceled or affirmed in an AIA trial, so there is no claim-level disposition to quote and no FWD to link. Claims 1–5 and every other claim stand as issued in the printed patent, unamended by any PTAB certificate. But that is an academic point: the patent issued 1997-05-27 from an application filed 1992-02-05 (priority claimed to 1990-08-29), giving it a pre-URAA seventeen-year term that ran out 2014-05-27 — the date Google Patents carries as the anticipated expiration and which the ODP legal-status field corroborates ("Expired – Lifetime"). A claim that is un-canceled but expired is not a defensible asset; it is a historical document.

Estoppel landscape: empty, and irrelevant. Because no IPR or PGR was ever instituted against this patent, § 315(e)(2) estoppel attaches to nobody — there is no petitioner, no privy, and no instituted ground set. That cuts both ways for a defendant: there is no body of PTAB-adjudicated art you inherit for free, and equally no petitioner-side estoppel constraining you. § 325(e) similarly has nothing to bite on. The real constraint on a defendant is temporal, not estoppel-based: under 35 U.S.C. § 286, damages reach back only six years from complaint filing, and because the patent expired 2014-05-27 and no suit is pending, that window is closed. A declaratory-judgment action on an expired patent would also face a live-controversy problem absent an extant royalty/licensing demand with continuing effect.

Pattern signals. (1) Same petitioner, multiple IPRs? No — no petitioner at all. (2) Aggressive PTAB appeals by the owner? Not on this patent; the Board never issued anything to appeal. (3) Defensive aggregator in the chain? I found no Unified Patents, RPX, or similar challenge connected to this patent. A Unified Patents portal page does list US-5633425-A among related Genpharm assets, but that is a patent-record entry, not evidence of a filed challenge — do not read it as one. (4) The institutional signal is instead about the patent family and its corporate lineage: Genpharm → Medarex → Amgen Fremont, with an extensive continuation family (e.g., US 5,625,126; 5,661,016; 5,770,429; 5,789,650; 5,874,299; 6,255,458; 6,300,129) and the European counterpart EP 0546073A1. Assertion risk today sits with the later, longer-lived family members, not with the 1997-vintage '425.

Recommended next steps

• If you have received a demand letter citing US 5,633,425: the dispositive response is expiration, not invalidity. The patent's term ended 2014-05-27 and 35 U.S.C. § 286 bars recovery for any infringement more than six years before a complaint is filed. Confirm the expiration date on the face of the patent and in PAIR/Patent Center, then state the defense in writing. Do not spend IPR budget on an expired claim — an IPR petition against a patent with no enforceable term is a waste of filing fees and attorneys' fees.
• If the assertion is instead against a family member (one of the later continuations with a term still running, or a non-US counterpart), that is a different analysis and none of the above applies. Run the proceeding check separately against each asserted patent number on the ODP AIA-trial endpoint and on PTAB E2E before assuming any of them is similarly clean.
• If you want the negative confirmed authoritatively: the ODP AIA-trial dataset is the canonical source and it is empty here. For belt-and-suspenders, pull the patent's full file history and any reexamination certificate through USPTO Patent Center, since reexamination outcomes are outside the AIA-trial dataset and I could only verify their absence by inference.
• If an active proceeding were pending (it is not, so this is hypothetical for this patent): the milestones to calendar are the § 314(b) three-month institution deadline, the statutory one-year trial clock from institution to FWD under § 316(a)(11), and the oral hearing roughly two months before the FWD date.
• Absence-of-activity caveat. Well-asserted patents eventually attract IPRs, so the total absence here is itself informative: 5,633,425 was commercialized in the 1990s and litigated (via sibling patents) while it was still young, then expired before the AIA-era IPR wave scaled up. There is no "survived two IPRs, therefore hardened" story to tell, and equally no "claims canceled, therefore dead" story — the only story is that the clock, not the Board, ended this patent.

Confidence note: I am highly confident in the "zero AIA proceedings" conclusion and in the 2014-05-27 expiration date as reported in the bibliographic record. I am not certain whether any pre-AIA ex parte or inter partes reexamination was ever filed on this patent; I found no evidence of one, but that is an inference from negative search results, not a confirmed fact, and the ODP block I was given covers AIA trials only.

I'll start by pulling what's verifiable from public sources, since I must not invent reel/frame numbers.

Provenance note: I could reach Google Patents' legal-events mirror of the USPTO assignment database and third-party/public sources, but I could not open Assignment Center or the USPTO assignment API in this session, so no reel/frame numbers, execution dates, or correspondents of record could be independently verified. Where a field is unverified I say so rather than supplying a number. Source: https://patents.google.com/patent/[US5633425](/patent/US5633425)/en#legalEvents

Inventors

• Both inventors are listed together on the parent priority filing (1990-08-29) and on this application (Ser. No. 07/834,539, filed 1992-02-05), and both are identified in the USPTO assignment record as the assignors of the 2004-09-21 recordation (see below).
• No "inventor-departure" pattern. The opposite is true: Lonberg and Kay continue to appear as the named inventors on Genpharm-assigned follow-on filings long after this patent issued — e.g., US 2006/0015949 A1 (filed 2004-12-10) and US 8,231,877 (filed 2010-04-29), both assignee GenPharm International, Inc., Milpitas CA. This is a cohesive, continuing in-house research team, not a group that walked out within 12 months of filing.
• Unusual pattern that is present: the family is built on an unusually small and stable two-inventor roster spanning roughly two decades of continuations and CIPs. The consequence for ownership analysis is that the equity in the whole family stayed with the company and was transferred as a block by corporate M&A, not by inventor-side sales.

Original assignee

Genpharm International, Inc. (California; addresses on the family front pages vary — Palo Alto, Mountain View, Milpitas and San Jose, CA — reflecting the company's moves, not separate entities).

• Line of business: transgenic-animal biotechnology for human antibody discovery. Genpharm is the originator of the HuMab-Mouse — mice carrying unrearranged human immunoglobulin heavy and light chain transgenes that undergo V(D)J rearrangement, class switching and somatic hypermutation. US 5,633,425 claims that mouse and the transgenes/methods behind it.
• Did it ship a product embodying the claims? Partially, and not in the ordinary sense. The "product" of the claims is a transgenic mouse strain, which Genpharm bred and used/supplied under collaboration and license agreements (Eisai, Centocor, LeukoSite per Medarex's 10-K). Genpharm never commercialized a therapeutic antibody itself; drugs made downstream using this platform include golimumab (Simponi), ustekinumab (Stelara), canakinumab (Ilaris), ipilimumab (Yervoy) and nivolumab (Opdivo).
• Current status: not independent and not dissolved. Per SEC merger documents, Genpharm's 1994 IPO was abandoned after a Cell Genesys trade-secret suit, and after shrinking through 1995–96 it was acquired by Medarex, Inc. on 1997-10-21 (deal valued at up to ~$65M in MEDX stock; announced May 1997 after a Cell Genesys/Abgenix/Xenotech/Japan Tobacco cross-license settled the litigation). Medarex was then acquired by Bristol-Myers Squibb Company, completed 2009-09-01, via tender offer plus short-form merger ($16.00/share; ~$2.4B). GenPharm International, Inc. continues to appear as a named assignee on filings as late as 2012, i.e. it persists as a BMS-held subsidiary/name rather than a standalone business.

Assignment timeline

Two recorded reassignment events appear for this patent, both dated 2004-09-21 in the legal-events record. USPTO reel/frame numbers, execution dates and the correspondents of record are not exposed by the source I could reach, and I did not verify them — I am not substituting estimates. This is the one material gap in this report; the fields are retrievable by searching this patent number in Assignment Center and reading the "correspondent" and reel/frame columns directly.

• Executed date: not retrieved / recorded 2004-09-21 — Reel not retrieved / not retrieved

  • Conveyance: Assignment of assignors' interest (recorded text: "ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS)")
  • Assignor: KAY, ROBERT M.; LONBERG, NILS
  • Assignee: GENPHARM INTERNATIONAL, INC. (a parallel entry renders the name "GENPHAM INTERNATIONAL, INC." — an apparent spelling/OCR variant of the same entity, not a second company; flagging it because a name-variant artifact is a classic source of false "shell entity" reads)
  • Correspondent: not retrieved (cannot flag recurrence; no finding either way)
  • Context: late/confirmatory recordation of the inventors' original assignment to the company — filed twelve years after the application and seven years after issuance, the signature of a due-diligence clean-up (portfolio review, license negotiation or financing) rather than a change of economic ownership.

• Executed date: not retrieved / recorded 2004-09-21 — Reel not retrieved / not retrieved

  • Conveyance: Assignment of assignors' interest (same descriptor)
  • Assignor: KAY, ROBERT M.; LONBERG, NILS
  • Assignee: GenPharm International, Inc. (second entry, same date and same assignor pair)
  • Correspondent: not retrieved
  • Context: duplicate/companion recordation of the same inventor-to-company transfer; the two same-day entries are most consistent with a corrected or bifurcated recording, not two distinct acquisitions.

No other assignments are recorded. In particular, no USPTO assignment record appears for either of the two economically decisive events:

• 1997-10-21 — Medarex, Inc. acquisition of GenPharm International, Inc. (mid-1997 deal; consummated 1997-10-21 per Medarex's 10-K). Ownership of the Genpharm patent estate passed with the merger.
• 2009-09-01 — Bristol-Myers Squibb Company acquisition of Medarex, Inc. (completed; short-form merger).

Both are documented in SEC/company filings but do not appear in the assignment events for this patent, which is common where title follows the corporate entity by operation of merger rather than by a recorded assignment instrument.

Timeline diagram

timeline
    title Ownership of US 5633425
    1990 : Priority application filed
    1992 : Application 07834539 filed
    1997 : Patent granted
         : Genpharm acquired by Medarex
    2004 : Inventor assignment recorded
    2009 : Medarex acquired by Bristol Myers Squibb
    2014 : Patent term expires

NPE / troll-pattern signals

1. Shell-entity transfer — not present. The only recorded assignee for this patent is GENPHARM INTERNATIONAL, INC. (2004-09-21 recordations), the original operating biotech. No "IP / Holdings / Ventures / Licensing" suffix entity appears; there is no single-purpose LLC, no registered-agent address, and no serviced-address pattern anywhere in the record.

2. Known asserter in the chain — not present. No entry in the chain matches Acacia, Marathon Patent Group, Intellectual Ventures, IPNav, Wi-LAN, Mosaid/Conversant, Vringo, Pendrell, Innovatio, MPHJ, Lumen View, Round Rock, Document Generation Corp, or any Spangenberg-linked entity. The chain terminates inside a top-20 pharmaceutical company.

3. Repeat correspondent across the chain — unclear / not determinable. Assignment Center did not expose the correspondent field in the source I reached, so there is nothing to count. For completeness, note the prosecution correspondents visible on the family: Townsend and Townsend and Crew LLP (agent of record on the sibling patent US 5,625,126) and Darby & Darby P.C., New York (correspondence address on later Genpharm applications such as US 2006/0015949 A1). Neither is an NPE-linked filer, and neither is a finding in the absence of a full correspondent readout for the 2004-09-21 recordings.

4. Cascading transfers — not present. One assignor pair, one assignee, one recording date (2004-09-21, entered twice). There is no series of chained transfers, no shared-address assignees and no sub-24-month chain to evaluate.

5. Pre-litigation transfer — not present / not applicable. I found no infringement suit naming US 5,633,425. The 2004-09-21 recording postdates issuance by roughly seven years, so it could not have been timed to a pleading. The only litigation context found is the defensive/competitive dispute in which Cell Genesys sued Genpharm in 1994, dismissed January 1997, settled March 1997 by a cross-license among Genpharm, Cell Genesys, Abgenix, Xenotech and Japan Tobacco — that is a competitor dispute involving the operating company, not an NPE assertion.

6. Bankruptcy fire-sale — not present. Genpharm sold from a position of strategic weakness — its own board minutes (in the Medarex proxy) state that without a larger partner's resources Genpharm "would not be able to develop its pharmaceutical products to the point of commercial viability" — but this was a negotiated stock-for-stock merger with a strategic buyer, not a Chapter 7/11 sale. No bankruptcy proceeding appears.

7. Privateering — not present. Transfers flow to operating biopharma (Genpharm → Medarex → Bristol-Myers Squibb) and the patents were monetized by licensing to partners (Eisai, Centocor, LeukoSite), not by arming an unrelated shell to sue the field.

8. Defensive aggregator — not present. No RPX, AST, LOT Network, Unified Patents or OIN entity appears in the chain; the inverse "neutralized" signal does not apply. This patent sits in a practicing pharmaceutical company's estate, which is a different form of non-assertion.

Verdict

Insufficient data — not a finding of NPE activity. The assignment record for US 5,633,425 contains only the inventor-to-company transfer recorded 2004-09-21 (assignors KAY, ROBERT M. and LONBERG, NILS; assignee GENPHARM INTERNATIONAL, INC./"GENPHAM INTERNATIONAL, INC."), which is the original assignment being recorded late, plus a same-day companion entry; under the rubric that is "only the original assignment," and I could not retrieve reel/frame or correspondent data to deepen it. All seven affirmative NPE signals are not present or not determinable, and the verifiable, filing-backed reality is that the chain runs Genpharm → Medarex (1997-10-21, per Medarex's 10-K and merger proxy) → Bristol-Myers Squibb (2009-09-01, per BMS's completion press release) — an operating-company chain with no post-issuance transfer to any third party.

Verify at: https://assignmentcenter.uspto.gov/ (search patent number 5633425; also https://patents.google.com/patent/US5633425/en#legalEvents) — read the reel/frame and correspondent columns to close the gap flagged above.

I'll research US patent 5,633,425 and its prior art citations. Let me start with searches.

Let me get the specific citation data for US 5,633,425 from patent databases.

I found a key source. Let me retrieve the complete "References Cited" list for US 5,633,425.

I've reached my search-step limit. Below is my analysis based on the sources I was able to retrieve, with explicit flags on what I could and could not verify.

Prior-Art Analysis — US 5,633,425

1. Patent identification (interpreting the number literally, as given)

Important scope caveat (per your strict rule): I did not auto-correct the secondary identifiers. The assignee string "GENPHAM INTERNATIONAL Inc" and "GENPHARM INTERNATIONAL, INC." both appear in the record; I report both as found.

2. Retrieval caveats — please read before relying on this

• I was able to retrieve the "References Cited" section of US 5,633,425 from the EveryPatent mirror (everypatent.com/comp/pat5633425.html). That list is dominated by (a) foreign patent documents and (b) non-patent literature (journal articles). The mirror's rendering did not expose a complete U.S.-patent citation list to me.
• I therefore cannot certify that the list below is the examiner's complete § 102 citation set. Treat it as the applicant/examiner citation list as published, not as a verified complete Form PTO-892.
• I was not able to retrieve the literal text of the claims of US 5,633,425. Accordingly, where you asked "which claim(s)," I identify the claim subject-matter categories that each reference could reach, and I explicitly flag that I could not map them to verified claim numbers. I will not invent claim numbers.

Two OCR artifacts appear in the source and are reproduced literally, not corrected, with the likely true identity noted only as a cross-reference for the reader:

• "Sniggemann et al PNAS 86:6709, 1989" — cross-referenced internally as the Bruggemann 1989 PNAS 86:6709-6713 hybrid mouse–human heavy chain paper.
• "Durdrh et al PNAS 86:2346, 1989" — cross-referenced internally as the Durdik et al. μ-heavy-chain transgene paper.

3. Cited foreign patent documents

No U.S. patent documents appeared in the reference list I retrieved. That is a material gap: for this era and this art unit, one would expect U.S. patent citations as well. I cannot confirm the absence of U.S.-patent citations — the mirror simply did not show them to me.

4. Cited non-patent literature (journal articles / texts)

5. Bottom-line § 102 assessment

1. Strongest § 102(b) candidates: Rusconi & Köhler 1985 (rearranged μ+κ transgenic mouse), Nussenzweig 1988 (allelic exclusion), Goodhardt 1987 (unrearranged rabbit κ rearranging in vivo), Bruggemann/"Sniggemann" 1989 (hybrid mouse–human heavy chain), Durdik 1989 (somatic mutation in a μ transgene), and the PCT publications WO 91/10741 and possibly WO 90/12840/12878 / WO 90/04036.
2. Reference that most likely is not available as § 102(b) art but is the most dangerous overall: Bruggemann et al., Eur. J. Immunol. 21:1323 (1991) (100 kb human IgH in mice) and WO 92/03918 (Mar. 1992) — both too close to the Feb. 5, 1992 filing to be § 102(b) art, and thus § 102(a)/(e)/§ 103 territory.
3. Claim categories most exposed to § 102: (a) transgenic non-human animal harboring a heterologous Ig transgene; (b) methods of producing heterologous antibody by immunizing such an animal; (c) B-cells/hybridomas expressing the transgene.
4. Claim categories least exposed (i.e., most likely novel over the cited art): the synthetic V-segment repertoire claims, the large-fragment / in vivo homologous-recombination transgene construction claims, the specific positive–negative-selection vectors for endogenous Ig-locus disruption, and the "two-antigen co-injection to sharpen affinity" method. No reference in the retrieved list appears to disclose these.
5. The '425 expressly distinguishes Goodhardt/Bruggemann-class art on the ground of "incomplete or minimal rearrangement," which is an anticipation-defeating argument under § 102 but simultaneously creates § 103 obviousness exposure.

6. What I could not verify (stated explicitly, per your rules)

• The complete U.S.-patent citation list (if any) for US 5,633,425 — not retrieved.
• The literal claim text and claim numbering of US 5,633,425 — not retrieved, so I have deliberately not assigned claim numbers.
• The actual content of EP 0 315 062, WO 90/04036, WO 90/12878, WO 91/00906, WO 91/10741, WO 92/03918, and of the "Karler" and "Sider" references — not verified; I have flagged each rather than characterizing it confidently.

If you can supply (or let me retrieve) the USPTO PatentCenter "References Cited" / Form PTO-892 image for 5,633,425, I can convert the above into a claim-by-claim § 102 chart with verified claim numbers.

I'll ground this analysis in the prior art of record and the actual claim language before building the § 103 combinations.

Preliminary notes, scope, and evidentiary limits

What I used as the "Prior Art section." The Google Patents page fetch for US 5,633,425 returned mostly navigation/image scaffolding; the substantive text is the specification (which discusses many of the same references) plus a classification table. The complete list of "Other References" of record (the prior-art list of record) was obtained from the USPTO-derived listing at https://uspto.report/patent/grant/[5,633,425](/patent/5633425). I treat that list as the authoritative prior-art set per your instruction.

Claim set analyzed (claims 1–7 as granted). Claim 1 is a product claim to a transgenic mouse whose germline contains an unrearranged human heavy-chain mini-locus (plurality of human V, plurality of human D, plurality of human J; a μ constant region with μ switch upstream of μ coding; and a γ constant region with γ switch upstream of γ coding), wherein the γ constant region is in closer proximity to the μ constant region than in the human locus, and which produces primary-response IgM⁺ B cells (VDJ-rearranged, with N-region nucleotides at V–D and D–J joints; FR1–FR3/CDR1–CDR2 derived from the mini-locus V segments) and secondary-response B cells in which class-switch recombination has joined the γ constant region to the rearranged V region, with the FR1–FR3/CDR1–CDR2 span containing a plurality of sequences not identical to the mini-locus (i.e., somatic hypermutation). Claims 2–7 add: segment-count ranges; the γ switch within a HindIII fragment that also contains a γ pre-switch sterile-transcript start site (claim 3); the ~5.3 kb γ1 HindIII fragment version (claim 4); the J–μ intronic enhancer (claim 5); a heavy-chain 3′ enhancer (claim 6); and secondary B cells lacking the μ coding region with μ switch contiguous to γ switch (claim 7).

Critical-date caveat (important, and it is dispositive of which references are available). Application 07/834,539 was filed 5 Feb 1992 and is a CIP of 07/575,962 (31 Aug 1990), itself a CIP of 07/574,448 (29 Aug 1990). The claims above — particularly the class-switch-recombination and "closer proximity than the human locus" limitations — are supported by the mini-locus constructs (pHC1/pHC2, pIGM1, pVGE1) disclosed in the 1992 CIP, not in the 1990 parents. If the § 103 critical date is therefore 5 Feb 1992 rather than 29 Aug 1990, additional art becomes available (notably Brüggemann et al., Eur. J. Immunol. 21:1323–1326 (1991), "Human antibody production in transgenic mice: expression from 100 kb of the human IgH locus"). I flag this because it materially changes the strength of the analysis; verifying the parent disclosures is required before relying on either date. I have not inspected the file wrapper, the examiner's reasons for allowance, or any interference record, and I do not assert their contents.

POSA. A scientist with a Ph.D. in immunology/molecular biology plus 2–5 years' hands-on transgenic-mouse/ES-cell experience, familiar with Immunoglobulin Genes (Honjo/Alt/Rabbitts 1989), Kabat, Hogan et al. (Manipulating the Mouse Embryo), and Sambrook.

The prior-art landscape (grouped by what it supplies)

Foreign patent documents listed: EP 0315062; WO 90/04036; WO 90/12878; WO 91/00906; WO 91/10741; WO 92/03918. I have not verified their contents, and I do not rely on them below.

§ 103 combinations

Graham factors applied: (1) scope/content of the art (above); (2) differences from claim 1; (3) PHOSITA level; (4) secondary considerations. Under KSR, the question is whether the combination was "obvious to try" with a reasonable expectation of success; in unpredictable biotech arts (In re Vaeck; Amgen v. Chugai), a mere "try it" with no directional teaching is generally insufficient.

Combination A — the mini-locus per se (bears on claim 1's first paragraph and claims 2, 5, 6)

Brüggemann 1989 PNAS + Goodhardt 1987 + Bucchini 1987 + Berman 1988 / Ichihara 1988 / Hofker 1989 + Jaenisch 1988 / Murray & Szostak 1983.

Brüggemann 1989 is the closest art: mice carrying "a human heavy-chain minilocus comprising unrearranged immunoglobulin variable, diversity, and joining elements linked to a human μ-chain gene"; rearrangement in thymus/spleen but not non-lymphoid tissue; ~4% of B cells synthesizing human μ; serum titer ~50 µg human IgM/ml; and hybridomas stably secreting human-μ antibodies (https://pubmed.ncbi.nlm.nih.gov/[2505258](/patent/2505258)/). Goodhardt 1987 shows an unrearranged heterologous light-chain gene (rabbit κ: single V, five J, Cκ) rearranging and expressing in mice, with secreted rabbit κ associating with mouse μ and γ1 (https://pubmed.ncbi.nlm.nih.gov/[3108888](/patent/3108888)/). Bucchini 1987 does the same for a chicken λ transgene.

Why combine: Brüggemann himself states the intended use — "Such transgenic mice could be used for the production of human monoclonal antibodies against human antigens" — and Buttin 1987 poses the identical strategy. The human V/D/J/C sequences and their RSSs were fully mapped (Berman, Ichihara, Hofker), and the patent itself treats RSS structure, N-region diversity, and gene-segment joining as well-known.

Result: A strong case that the μ-only mini-locus mouse (rearranging human V–D–J, expressing human μ, with N-regions at the joints) was obvious.

Combination B — adding the γ constant region + switching (claims 1, 3, 4, 7)

Combination A + Durdik 1989 + O'Brien 1987 + Yasui 1989 + Sideras 1989 + Nikaido 1981/1982, Mowatt 1986, Rabbitts 1981, Ravetch 1980 + Yamamura 1986.

Durdik 1989 showed (i) somatic mutation in the V region of a μ heavy-chain transgene and (ii) that a high proportion of transgenic B cells expressed the transgene-encoded V region associated with IgG rather than IgM, i.e., isotype switching of a transgene. O'Brien 1987 showed hypermutation of a 15 kb κ transgene in hyperimmunized mice. Yasui 1989 disclosed the human σμ/Σμ direct repeats flanking the μ gene and the homologous-recombination mechanism deleting μ in IgD-only cells; Nikaido/Ravetch/Rabbitts disclosed the switch-region repeat structure and the fact that recombination occurs between switch segments at variable positions. Crucially, the patent's own specification concedes the predictive link: "The ability of a transgene construction to switch isotypes during B-cell maturation has not been directly tested in transgenic mice; however, transgenes should carry out this function." Under KSR, an applicant's own admission that the result "should" follow is powerful evidence that a POSA had a reasonable expectation of success. Add Yamamura 1986 (a human γ1 constant region, including switch, expressed from a transgene in mice).

Motivation: therapeutic antibodies require IgG, not IgM (Morrison 1984; Brüggemann JEM 1989). Result: claims 1, 3, 4 and 7 are exposed to a substantial § 103 attack.

Claims 3 and 4 face the strongest attack. The claim 4 element — an ~5.3 kb human HindIII fragment containing the γ1 switch region and the start site of the γ1 pre-switch sterile transcript — is, on the face of the specification, the prior-art fragment: the patent itself cites Sideras et al., Int. Immunol. 1:631 (1989) for exactly that sterile-transcript element and isolates the fragment from a human library. Standing alone, that element is disclosed in the art; only its incorporation into a class-switching transgenic mouse saves these claims.

Combination C — enhancers (claims 5, 6)

Combination B + Banerji 1983 / Hayday 1984 / Mills 1983 (J–μ intronic enhancer) + Pettersson 1990 (rat IgH 3′ enhancer). Both elements and their use to elevate Ig transgene expression were known; the patent's own claims 5–6 recite them as additions to the claim 1 mouse. Motivation: overcome the low transgene expression levels reported by Brüggemann 1989 and Goodhardt 1987 (Goodhardt reported "low" transcription "despite a high level of rearrangement") in order to drive allelic exclusion and a usable repertoire.

Combination D — endogenous-locus knockouts (specification's preferred embodiment)

Combination A/B + Zijlstra 1989 + Mansour 1988 + Thomas & Capecchi 1987 + Capecchi 1989.

Zijlstra 1989 is the direct template: homologous recombination in ES cells producing a disrupted β2-microglobulin allele with germ-line transmission in chimeric mice (https://pubmed.ncbi.nlm.nih.gov/[2685607](/patent/2685607)/). Mansour 1988 supplies the neo-positive/HSV-tk-negative selection architecture the patent copies. The patent concedes that only three disruptions are needed (the mouse λ locus contributes ~5% of Ig) and that the mouse J_H region "is fairly compact… spanning only 1.3 kb" — i.e., an easy target.

Motivation: Goodhardt's data show the interference problem (hybrid antibodies containing both rabbit and mouse κ), and the patent itself allows that if endogenous loci are disrupted "the transgene need not activate allelic exclusion." Result: the knockout-plus-mini-locus embodiments are highly vulnerable under § 103.

Combination E — if the critical date is 5 Feb 1992 (CIP claims)

Add Brüggemann 1991, Eur. J. Immunol. 21:1323 (expression from 100 kb of the human IgH locus) and Brüggemann & Neuberger, Methods 2:159 (1991). If the 1991 100 kb transgene in fact carried both μ and γ constant genes (I could not verify this from the available text — treat as an open question requiring the full paper), it would come closer to claim 1's structural element, although it would retain the native order and spacing and therefore would still not disclose the "closer proximity than in the human locus" limitation.

Why the claims may nonetheless withstand § 103 (the applicant's case)

1. The art taught away from faithful mini-locus function. Goodhardt's own conclusion was that "sequences implicated in stage- and tissue-specific regulation of κ chain gene rearrangement are either missing or not recognized by mouse lymphoid cells." The patent characterizes the field results as "variable, in some cases, producing incomplete or minimal rearrangement of the transgene." Brüggemann 1989 achieved only ~4% of B cells and ~50 µg/ml IgM, with no γ constant region, no demonstrable class switching, and no demonstration of somatic mutation.
2. The "closer proximity than the human locus" element is not taught or suggested. Every reference of record places μ and γ in their native chromosomal relationship, or uses a μ-only mini-locus. Deliberately juxtaposing γ at non-native proximity to μ required construction choices (inclusion of the γ1 5′ flanking region, the J–μ enhancer, the rat 3′ enhancer, and the σμ/Σμ elements) not directed by the art. The patent's stated rationale — that upstream cis-acting sequences "are often important for transcription regulation" of the sterile transcript — reflects residual unpredictability about the minimum cis elements required for switching.
3. Unexpected breadth of repertoire from a small mini-locus. The premise that a handful of V segments suffices for a T-cell-dependent response (which the patent reasons by analogy to the rabbit) was counterintuitive; contemporary commentary on the Brüggemann approach emphasized "relatively weak" serum responses, i.e., the art expected mini-loci to be poor.
4. Secondary considerations. Long-felt need and failure of alternatives (rodent MAbs and human hybridomas; chimeric antibodies remained immunogenic per Brüggemann JEM 1989; CDR grafting required a pre-existing rodent MAb); the decisive demonstration did not appear in the literature until Lonberg et al., Nature 368:856 (1994), years after the 1990/1992 filings; and the technology underpinned a commercial human-antibody platform (XenoMouse®-derived panitumumab; Medarex-derived fully human antibodies such as ipilimumab/nivolumab) — I state the product attributions with moderate confidence; commercial-success evidence would need to be documented properly in any brief.
5. Product-claim caution. Claim 1 recites functional characteristics (class switching and somatic hypermutation in secondary-response B cells). Obviousness of such a claim normally requires that the art's product either possess those characteristics or that they be expected with reasonable certainty — not merely that the DNA elements were individually known. The patent's contrary admission ("transgenes should carry out this function") cuts the other way and is the single most damaging statement to the applicant's position.

Bottom line

• Strongest § 103 combinations: (i) Brüggemann 1989 + Goodhardt 1987 + Bucchini 1987 + published human Ig gene maps + standard microinjection → obviousness of the μ-only, rearranging human mini-locus mouse; (ii) that combination + Durdik 1989 + O'Brien 1987 + Yasui 1989 + Sideras 1989 + switch-region/Nikaido-Ravetch art + Pettersson 1990 → obviousness of the class-switching/somatically-mutated γ-bearing mini-locus mouse; (iii) either of the above + Zijlstra 1989 + Mansour 1988 + Capecchi/Thomas → obviousness of the knockout-plus-transgene embodiments.
• Most vulnerable claims: 3 and 4 (their DNA element is expressly attributed in the specification to a cited prior-art reference, Sideras 1989), and 5 and 6 (Banerji/Hayday/Mills; Pettersson 1990).
• Strongest non-obviousness redoubt: the deliberate non-native juxtaposition of μ and γ switch regions to yield cis-class switching plus de novo somatic hypermutation in the same animal, coupled with the contrary/limited prior-art results (Goodhardt's conclusion, Brüggemann's 4% B cells, the absence of any prior report of a successful isotype-switching heterologous transgene), the long-felt need, and the eventual commercial validation.

Unverified items you should confirm before filing anything: (1) whether the granted claims are entitled to the 29 Aug 1990 date or only to 5 Feb 1992 (CIP new-matter analysis of the parent applications); (2) the actual content of Brüggemann 1991 (does the 100 kb transgene carry Cγ?); (3) the contents of WO 90/04036, WO 90/12878, WO 91/00906, WO 91/10741, EP 0315062; (4) the examiner's reasons for allowance and any interference/reexamination record. I was unable to complete verification of items (2)–(4) within this session.