US 5510486

I'll search for authoritative records on this specific patent number before summarizing.

Let me check for any CAFC 2026 litigation involving this specific patent.

Search scope and results

I searched for the literal identifier 5510486 (US 5,510,486 / US 5510486 A, application 08/280,265). Searches returned the Google Patents record for US5510486A, a Unified Patents portal record for US-5510486-A, and multiple later Helsinn palonosetron patents that cite it as prior art (e.g., US 8,623,826 lists "5,510,486 A 4/1996 Robinson, III et al."). I found no CAFC 2026 docket referencing this patent number; the Federal Circuit palonosetron appeals I located involve different patents (the '724/'725/'424/'219/'094 patents, e.g., Helsinn v. Teva, 855 F.3d 1356 (Fed. Cir. 2017)). Treat the absence of a 2026 CAFC case as a negative finding, not a positive confirmation.

Note on the identifier: the granted patent prints the number as 5,510,486; Google Patents renders it US5510486A. These are the same document.

Bibliographic summary

Uncertainty: Unified Patents lists the priority date as 1994-07-25, the grant date as 1996-04-22, and expiration as 2014-07-25 — one day earlier than the Google Patents/USPTO dates of 1994-07-26 / 1996-04-23 / 2014-07-26. I have used the Google Patents values (which match the patent front page and the "Anticipated expiration 2014-07-26" entry), but flag the one-day discrepancy.

Abstract (as printed)

"This invention relates to a process for preparing 2-(1-azabicyclo[2.2.2]oct-3-yl)-2,3,3a,4,5,6-tetrahydro-1H-benz[de]isoquinolin-1-one, particularly 2-(1-azabicyclo[2.2.2]oct-3S-yl)-2,3,3aS,4,5,6-tetrahydro-1H-benz[de]isoquinolin-1-one, and to intermediates useful in such process."

The compound produced is palonosetron (marketed as Aloxi®), a 5-HT₃ receptor antagonist.

Plain-language overview of the independent claims

The patent has 8 claims total: three independent claims (1, 4, 7) and five dependent claims (2, 3, 5, 6, 8). The three independents are nested subsets of the same four-step synthesis — claim 1 covers all steps, claim 4 starts after the amide-forming step, and claim 7 covers only the final cyclization. Each independent claim ends with parallel "optionally" steps for separating stereoisomers, forming an acid-addition salt, and converting a salt back to free base. Those optional steps are recited as optional and do not narrow the claim.

Claim 1 — full process (four steps).
A method of making palonosetron (and its salts/stereoisomers) by:

• (A) reacting a compound of Formula 5 (a 1,2,3,4-tetrahydro-1-naphthoic acid derivative bearing a leaving group L, i.e., an activated naphthoyl compound) with 1-azabicyclo[2.2.2]oct-3-ylamine (quinuclidin-3-amine) to form N-(1-azabicyclo[2.2.2]oct-3-yl)-1,2,3,4-tetrahydronaphthalen-1-ylcarboxamide (an amide);
• (B) reducing that carboxamide to the corresponding amine, (1-azabicyclo[2.2.2]oct-3-yl)(1,2,3,4-tetrahydronaphthalen-1-ylmethyl)amine;
• (C) reacting that amine with a formylating agent (e.g., trichloromethyl chloroformate/phosgene-type reagent) and then treating with a Lewis acid (e.g., BF₃·OEt₂) to cyclize to the tricyclic lactam palonosetron;
• followed by the optional steps (D) stereoisomer separation, (E) salt formation, and (F) desalting.

Claim 4 — process starting from the pre-made amide. Same overall goal, but step (A) is omitted: the process begins by reducing N-(1-azabicyclo[2.2.2]oct-3-yl)-1,2,3,4-tetrahydronaphthalen-1-ylcarboxamide to the amine, then formylating/Lewis-acid cyclizing, plus the same optional steps. This claims the downstream half of the route independent of how the amide was made.

Claim 7 — process starting from the pre-made amine. Narrowest independent claim: only the formylation + Lewis-acid cyclization of (1-azabicyclo[2.2.2]oct-3-yl)(1,2,3,4-tetrahydronaphthalen-1-ylmethyl)amine to palonosetron, plus the same optional steps. This is the key ring-closing step.

Dependent claims:

• Claim 2 (dep. on 1): narrows to L = chloro (the acid chloride) and (S)-1-azabicyclo[2.2.2]oct-3-ylamine, giving the 3S-amide.
• Claim 3 (dep. on 2): further narrows the amide to the 1S diastereomer, N-(1-azabicyclo[2.2.2]oct-3S-yl)-1,2,3,4-tetrahydronaphthalen-1S-ylcarboxamide.
• Claim 5 (dep. on 4): the starting amide is the 3S enantiomer.
• Claim 6 (dep. on 5): the starting amide is the 3S,1S diastereomer.
• Claim 8 (dep. on 7): the starting amine is (1-azabicyclo[2.2.2]oct-3S-yl)(1,2,3,4-tetrahydronaphthalen-1S-ylmethyl)amine.

Claims 2, 3, 5, 6 and 8 progressively lock the process onto the single stereochemistry that yields the marketed (3S,3aS) palonosetron isomer.

Notes on status and litigation relevance

• The '486 patent is expired (anticipated expiration 2014-07-26), so it is no longer enforceable or assertable. It cannot be the subject of a live 2026 CAFC appeal on its own claims.
• Its significance today is primarily as background/prior art describing a palonosetron synthesis. It is cited on the face of later Helsinn patents (e.g., US 8,623,826 B2, "Compositions and methods for treating centrally mediated nausea and vomiting," assignee Helsinn Healthcare S.A.) and in foreign counterparts/generic-filing documents (e.g., CN 101314601 A discusses recrystallizing palonosetron HCl per the process of "U.S. Patent No. 5,510,486").
• The Helsinn palonosetron litigation that reached the Federal Circuit and Supreme Court concerned different patents (the formulation/dose patents '724, '725, '424, '219, '094), not the '486 process patent. I found no record tying '486 to a CAFC 2026 docket.

Explicit uncertainties

1. CAFC 2026 dockets: My searches surfaced no 2026 Federal Circuit case involving US 5,510,486. I cannot positively confirm a "no 2026 litigation" conclusion from search results alone — it is simply an absence of evidence. A docket-level query (e.g., PACER/CAFC CM/ECF by patent number) would be needed for certainty.
2. Exact priority/expiration dates: One-day discrepancy between sources, as noted above.
3. Reassignment/terminal-disclaimer details: The AIA/URAA term-extension and any terminal disclaimer history for the '486 patent are not fully visible in the retrieved record; only the "Expired – Lifetime" status and the 2014 anticipated expiration are shown.
4. Chemistry reading of the claims: The above is a plain-language characterization of the claimed steps based on the specification and examples; the claim language controls, and I have not independently verified the structures of "Formula 5" beyond what the specification states.

I'll search for litigation involving US patent 5510486 across litigation databases.

Let me search the litigation databases more specifically.

Let me check the Unified Patents litigation portal directly for this specific patent and search for any assertion records.

Litigation search: US Patent No. 5,510,486

Bottom line

I found no litigation that specifically asserts or involves US Patent No. 5,510,486 (the process patent for preparing palonosetron, "Process for preparing 2-(1-azabicyclo[2.2.2]oct-3-yl)-2,3,3a,4,5,6-hexahydro-1H-benz[de]isoquinolin-1-one").

I want to be explicit about a key distinction, because the search results are easy to misread: Helsinn Healthcare S.A. (the eventual owner of the '486 patent) has been a very active patent litigant over palonosetron/Aloxi®, but those cases were not brought on the '486 patent. They were brought on later, different patents in the same portfolio (US 7,947,724; 7,947,725; 7,960,424; 8,598,219; 8,729,094 — and later the Akynzeo® patents).

What the '486 patent actually is

Source: https://patents.google.com/patent/[US5510486A](/patent/US5510486A)/en and https://portal.unifiedpatents.com/patents/patent/US-5510486-A

Litigation known for this patent (5510486)

None identified. No district court case, CAFC appeal, ITC action, or PTAB/IPR proceeding naming US 5,510,486 as a patent-in-suit appeared in my searches. The Unified Patents patent detail page for US-5510486-A lists no litigation and no opposition documents. Given the patent's July 2014 expiration, it would not have been available to assert in the 2015–2018 ANDA wave against generic palonosetron.

Litigation I did find (different patents — flagged so you don't conflate them)

So you have the full picture of Helsinn's palonosetron enforcement, which is frequently discussed alongside the '486 family but does not involve the '486 patent:

Sources: https://www.eisai.com/news/pdf/enews201577pdf.pdf ; https://www.finnegan.com/a/web/56530/2G4oFc/20151113_311cv03962_helsinn_v_teva_di360_memorandum_opinionpd.pdf ; https://www.robinskaplan.com/printpilot-publication-resources-legal-updates-generically-speaking-hatch-waxman-bulletin-2015-generically-speaking-winter-2015-helsinn-healthcare-sa-v-dr-reddys-labs-ltd2.pdf ; https://storage.courtlistener.com/recap/gov.uscourts.njd.[351305](/patent/351305)/gov.uscourts.njd.351305.71.0.pdf

Caveats and how to confirm

• My search was not exhaustive; I was cut off by a step limit while attempting to load the Unified Patents litigation caselist filtered to this exact patent (https://portal.unifiedpatents.com/litigation/caselist?patents=5510486). That filtered view, plus a PACER docket search and a CAFC docket search, would be the authoritative confirmation.
• The only textual hit pairing "5510486" with litigation-adjacent material was a different patent ('048, i.e., 6,871,048, a Research In Motion/Rydbeck matter) and an unrelated product code — none of which concern US 5,510,486. I did not treat those as matches.

If you need certainty for a validity/enforceability or freedom-to-operate file, I'd recommend pulling the Unified Patents caselist filtered on patent number 5510486, a Docket Alarm / Lex Machina patent-level query, and an RPX litigation search before recording "no litigation."

I'll verify the structured "no proceedings" finding against public sources before drafting.

Let me run a few more targeted checks (pre-AIA reexam, any PTAB numbering, and Helsinn's '486-specific activity).

Two final confirmations — checking aggregator/PTAB docket indexes for the '486 patent specifically.

Proceedings overview

Total AIA trial proceedings on US 5,510,486: zero (0 active, 0 claims invalidated, 0 claims sustained, 0 settled, 0 institution denials). The USPTO Open Data Portal structured block returns no AIA trial proceedings for this patent, and my independent searches of Google Patents, Unified Patents' patent portal (US-5510486-A), and DrugPatentWatch's palonosetron PTAB index (PALONOSETRON HYDROCHLORIDE) surface no IPR, PGR, or CBM naming this patent — so the per-proceeding template below is intentionally unpopulated rather than filled with guesses. The defensive posture this gives a defendant is not "hardened patent" and not "claims canceled" — it is a third thing: moot. The '486 patent expired 2014-07-26 and was never tested at the Board, so there is nothing to institute against and nothing to inherit. Any demand letter citing US 5,510,486 should be answered on expiration/limitations grounds, not with a PTAB strategy.

No proceedings on file — how I verified it

• Canonical source (controlling): the structured ODP block in this prompt states no AIA trial proceedings are on file.
• Corroborating negative finding: every palonosetron PTAB case I could locate is keyed to a different patent number. DrugPatentWatch's palonosetron PTAB table lists only US 8,598,219, US 8,729,094, and US 9,173,942 — petitioners Accord Healthcare and Dr. Reddy's, various 2014–2016 filing dates. None is US 5,510,486.
• Sibling-patent context (NOT proceedings on the '486 — do not cite them as if they were):

I could not retrieve trial numbers, institution outcomes, or claim-level dispositions for these three from the sources available to me, and I will not invent them. The "decision date" column as published by the aggregator most likely reflects institution decisions, not Final Written Decisions — treat it as unverified. These are listed solely to show that challengers were active in this drug family and still never touched the '486.

Strategic summary

Claim status: all 8 claims UNTESTED, and all 8 EXPIRED. Claims 1, 4, and 7 (the three independents) and dependents 2, 3, 5, 6, and 8 were never canceled, never confirmed, and never construed by the Board. Because no FWD ever issued, there is no claim-level record to quote — I am not going to dress up an absence as a holding. The practical corollary is that a defendant cannot point to "claims 1–5 canceled" (the framing the task template anticipates for a defeated patent); the correct reframe is that the entire patent lapsed for failure to maintain/term expiry on 2014-07-26, per the "Anticipated expiration" legal-status event in the Google Patents record (US5510486A).

Estoppel landscape: there is none, in either direction. Section 315(e)(2) estoppel attaches only to a petitioner that obtains a Final Written Decision. With no IPR on this patent, no petitioner is estopped, no privy is estopped, and no district court can invoke IPR estoppel against a '486 invalidity defense. Conversely, there is no PTAB record for a patent owner to hide behind under § 325(d) or Advanced Bionics. If you needed to invalidate the '486 in court for some historical reason, the full universe of prior art is still available — including the very references on the face of the patent (US 5,202,333 and US 5,202,318, both Syntex) and the Morrison & Boyd Organic Chemistry citation in the "Non-Patent Citations" block. None of it has been "reasonably could have raised"-consumed by anyone.

Pattern signals: the '486 was structurally un-challengeable in practice, not merely unchallenged. Three things converge. First, timing: the patent expired 2014-07-26, and the first palonosetron PGR was filed weeks later (2014-09-02) against a different patent — IPR/PGR practitioners had no economic reason to spend on a process patent whose term was already over. Second, target selection: Helsinn's ANDA wars were fought over the formulation/dose patents ('724, '725, '424, '219, '094), which carried the 2024-ish runway; the '486 was a synthesis patent that had already been superseded in the literature and in generics' own process development (see, e.g., the Chinese process filings that describe the '486 route as the prior art being improved upon). Third, no aggregator: I found no Unified Patents proceeding on the '486. Unified's portal does host a descriptive page for US-5510486-A, but a patent page is not a filed petition — I flag this explicitly because the earlier summary in this analysis also noted the Unified record, and a reader could mistake it for an IPR filing. It is not one. There is also no CBM to speak of: CBM review was limited to covered business methods, categorically inapplicable to a quinuclidine synthesis patent.

One contradiction to flag against the earlier section. The prior section reported the CAFC palonosetron appeals as involving "the '724/'725/'424/'219/'094 patents, e.g., Helsinn v. Teva, 855 F.3d 1356 (Fed. Cir. 2017)." My search results independently confirm that framing — the Federal Circuit's 2017 on-sale-bar decision invalidated claims of the '724, '725, '424, and '219 patents, and the Supreme Court affirmed at Helsinn Healthcare S.A. v. Teva Pharmaceuticals USA, Inc., 586 U.S. 123 (2019) (CourtListener). Nothing in that line of cases touches the '486. No contradiction found on this point.

Recommended next steps

If you are a defendant and the demand letter cites US 5,510,486: the response is not a PTAB filing — it is a calendar. The patent expired 2014-07-26 (Google Patents legal-status entry "Anticipated expiration 2014-07-26"; Unified Patents shows 2014-07-25 — see the one-day discrepancy carried forward from the earlier section and use the later Google/USPTO-front-page date). Expiration means (a) no prospective infringement for acts after that date, (b) no injunction available, and (c) damages, if any, limited by 35 U.S.C. § 286 to six years before the complaint — a window that closed around 2020. In practical terms, a 2026 demand letter invoking this patent is either a mistake or a bluff. Push for the specific accused acts and their dates before engaging on the merits.

If you were considering an IPR of the '486: do not. Congress and the Board permit IPR of expired patents in narrow circumstances, but there is no claim scope worth invalidating, no royalties to moot, and no § 315(b) clock to beat because there is no live assertion to answer. Money spent here is money burned.

If a demand letter cites a different Helsinn palonosetron patent: recognize that you may be looking at a patent that did go through PTAB — the '219, '094, and '942 patents all have Board history per DrugPatentWatch, and the '724/'725/'424/'219 set was invalidated on-sale-bar at the Federal Circuit and affirmed by the Supreme Court in 2019. Those are separate dockets with separate outcomes, and I have deliberately not attributed any FWD language or claim-level verdict to them because I could not retrieve the underlying decisions. Before relying on any of them, pull the actual papers from PTAB E2E (https://ptab.uspto.gov) by trial number — that docket-level query is the one step I could not complete here.

Verify before you rely on the negative finding. My "no proceedings" conclusion rests on the ODP structured block plus three independent aggregator searches that all returned the same result. It is a strong negative, but the only way to convert it from absence-of-evidence to certainty is a docket-level query of USPTO PTAB E2E / Patent Center for application 08/280,265 and patent 5,510,486, plus a PACER check for any pre-AIA inter partes reexamination (which ODP's AIA-trial dataset does not cover). I did not find a reexam record either, and I am explicitly flagging that as an unverified negative rather than a confirmed one.

I'll research the USPTO assignment records and cross-reference sources for this patent.

Assignment‑Chain Analysis — US 5,510,486

Method note / limitation up front: I was able to retrieve two recorded assignments (with reel/frame and dates) from the Google Patents legal‑events feed, which mirrors the USPTO Patent Assignment Search database. I was not able to pull the raw Assignment Center record images, so the correspondent‑of‑record fields are not available to me and are marked [not retrieved] rather than guessed. See verification instructions at the end.

Inventors

Unusual‑pattern check: Not present. All three inventors executed a standard employment assignment to the same corporate employer, and there is no evidence in the record of inventor departure within 12 months of filing. The key corroborating fact is the execution date = filing date (1994‑07‑26), i.e., the inventors assigned to the company before patent rights vested — the classic operating‑company employment pattern, not a post‑hoc acquisition of individual rights.

(I cannot affirmatively confirm the inventors' later employment history; no data retrieved.)

Original assignee

Syntex (U.S.A.) Inc. (rendered elsewhere as "Syntex USA LLC"), a U.S. subsidiary of Syntex Corp.

• Primary line of business: Research‑based pharmaceutical manufacturer (anti‑inflammatories, steroids, Naprosyn®, oral contraceptives).
• Did it ship a product embodying the claims? Yes — the patent is a process for making palonosetron, a 5‑HT₃ antagonist. Syntex discovered palonosetron; Syntex/Roche held the development rights. (Commercial launch ultimately occurred under Helsinn as Aloxi®.)
• Current status: Acquired, no longer operating as "Syntex." Syntex Corp. was acquired by Roche Holding AG in 1994 (~$5.3 billion). Note the timing: the inventors' assignment was recorded 1994‑09‑12, during the Roche/Syntex integration window, but the assignee of record is still Syntex (U.S.A.) Inc., consistent with a subsidiary‑level recordal.
• Role of the 1999 transfer: Syntex (U.S.A.) Inc. assigned the patent to Helsinn Healthcare SA effective 1999‑03‑15 — consistent with a divestiture of the palonosetron asset following the Roche acquisition. Helsinn is a Swiss operating pharmaceutical company that commercializes Aloxi® (palonosetron HCl) and later Akynzeo®.

Assignment timeline

Two recorded assignments. No license recordations, no security agreements, no merger/change‑of‑name filings, no releases.

1. 1994‑07‑26 (executed) / recorded 1994‑09‑12 — Reel 007124/0603

• Conveyance: Assignment
• Assignor: Robinson, James III; Rohloff, John Christian; Kowalczyk, Bruce Andrew (the inventors)
• Assignee: Syntex (U.S.A.) Inc. (California)
• Correspondent: [not retrieved]
• Context: Initial employment/inventor assignment — standard "assignors' interest" recordal capturing the inventors' rights in the application.

2. 1999‑03‑15 (executed) / recorded 1999‑04‑02 — Reel 009875/0015

• Conveyance: Assignment
• Assignor: Syntex (U.S.A.) Inc.
• Assignee: Helsinn Healthcare SA (Switzerland)
• Correspondent: [not retrieved]
• Context: Corporate asset acquisition/divestiture — transfer of the palonosetron patent rights (with the sibling divisional US 5,576,434 / app 08/590,848) from the Roche‑controlled Syntex entity to the operating brand company Helsinn.

Gap flagged: USPTO Assignment Center exposes a correspondent (attorney/agent) field for each record. If the two reels above share the same correspondent/firm, that would be worth noting — but I could not retrieve those fields, so I make no recurrence finding (Signal 3 = incomplete).

Timeline diagram

timeline
    title Ownership of US 5510486
    1994 : Filed by Syntex USA
         : Inventors assign to Syntex
    1996 : Patent granted
    1999 : Syntex assigns to Helsinn Healthcare
    2014 : Patent expires

NPE / troll‑pattern signals

1. Shell‑entity transfer — NOT PRESENT. Apex assignee is Helsinn Healthcare SA, a Swiss operating pharma with a marketed product (Aloxi®). No "IP / Licensing / Holdings / Ventures" suffix; no registered‑agent‑service address. (Reel 009875/0015.)

2. Known asserter in the chain — NOT PRESENT. Neither Syntex (U.S.A.) Inc. (Reel 007124/0603) nor Helsinn Healthcare SA (Reel 009875/0015) matches any public NPE list (Acacia, Marathon, IV, IPNav, Wi‑LAN, Conversant, Vringo, Pendrell, Round Rock, etc.). Helsinn appears in Hatch‑Waxman litigation as the brand/plaintiff manufacturer, i.e., the inverse of an NPE posture.

3. Repeat correspondent across the chain — UNCLEAR (data gap). Only two assignments exist, and the correspondent fields were not retrievable. No recurrence can be confirmed or excluded on the evidence gathered.

4. Cascading transfers — NOT PRESENT. Two assignments over ~5 years through two unrelated, named operating companies — not a chain of single‑purpose LLCs sharing an address. (Reels 007124/0603 and 009875/0015.)

5. Pre‑litigation transfer — NOT PRESENT. The last transfer (effective 1999‑03‑15) predates the Helsinn palonosetron generic litigation by roughly 14–15 years — far outside any 6‑month pre‑suit window. I also found no record of US 5,510,486 itself being asserted; the Federal Circuit palonosetron appeals (Helsinn v. Teva, 855 F.3d 1356 (Fed. Cir. 2017)) concerned the formulation/dose patents (the '724/'725/'424/'219/'094 family), not this process patent.

6. Bankruptcy fire‑sale — NOT PRESENT. No Chapter 7/11 proceeding involving Syntex or Helsinn surfaced. The Syntex→Roche outcome was a merger/acquisition, and the later Syntex→Helsinn transfer was a negotiated product‑rights sale, not a distressed sale.

7. Privateering — NOT PRESENT. The 1999 transfer moved the asset to the party that commercialized palonosetron (Helsinn), not to a separate assertion vehicle; there is no evidence of an operating company funding an NPE to sue its competitors here.

8. Defensive aggregator (anti‑NPE) — NOT PRESENT. The chain terminates at an operating brand company, not RPX, AST, LOT Network, Unified Patents, or OIN.

Verdict

Operating‑company assertion.

The chain is a clean, two‑link corporate transfer — inventors → Syntex (U.S.A.) Inc. (Reel 007124/0603, executed 1994‑07‑26, recorded 1994‑09‑12) → Helsinn Healthcare SA (Reel 009875/0015, effective 1999‑03‑15, recorded 1999‑04‑02) — with zero NPE signals present and the asset held at the end by a Swiss brand manufacturer that ships palonosetron (Aloxi®) and has itself litigated as the brand plaintiff against generics. Caveat: US 5,510,486 expired on/around 2014‑07‑26 and I found no evidence it was ever asserted on its own claims, so its practical role today is background/prior art (it is cited on the face of later Helsinn patents, e.g., US 8,623,826 B2, and in foreign filings such as CN 101314601 A) rather than an assertion instrument.

Verify at: https://assignment.uspto.gov/patent/index.html (search patent number 5510486) or https://assignmentcenter.uspto.gov/ — specifically retrieve Reel 007124/0603 and Reel 009875/0015 to capture the correspondent‑of‑record fields I could not retrieve.

Explicit uncertainties

1. Correspondent fields are unverified for both reels — I did not fabricate names. Signal 3 is therefore reported as unclear, not absent.
2. One‑day date discrepancies persist between sources (Google Patents shows priority/expiration 1994‑07‑26 / 2014‑07‑26; Unified Patents shows 1994‑07‑25 / 2014‑07‑25), as flagged in the earlier summary. I used the Google Patents/USPTO‑front‑page values.
3. Roche/Syntex relationship is stated from general knowledge of the 1994 Roche acquisition of Syntex Corp.; I did not retrieve a primary SEC/Roche filing in this session, so treat the "Roche‑controlled parent" characterization as high‑confidence background rather than a record‑cited fact.
4. No evidence of inventor departures is a negative finding from the assignment record only, not an affirmative confirmation of continued employment.

I'll search for authoritative records on US 5,510,486 and each of its cited references.

I have the '486 record and the '333 reference. Let me now pull details on the second cited patent (US 5,202,318) and the non-patent literature.

I have solid records on both cited patents. Let me verify the process chemistry disclosed in US 5,202,333 (the closest reference) to assess anticipation properly.

Prior-Art Analysis for US 5,510,486 (Application 08/280,265)

Scope note: I searched the USPTO record for the literal number 5510486 and did not return adjacent numbers. The authoritative record I could retrieve is the Google Patents/USPTO front page for US5510486A (https://patents.google.com/patent/US5510486/en) plus the EveryPatent mirror (http://www.everypatent.com/comp/pat5510486.html) and the Unified Patents portal record (https://portal.unifiedpatents.com/patents/patent/US-5510486-A). The "References Cited" section of the '486 front page lists exactly two U.S. patent citations and one non-patent reference (the NPL entry is duplicated in the OCR). A separate family-level entry (US4920227A) also appears and is treated below.

Critically, this is a process patent: independent claims 1, 4 and 7 are method claims. Under pre‑AIA 35 U.S.C. § 102, a reference anticipates only if it discloses each and every step arranged as in the claim. A composition/compound patent that discloses the product does not, without more, anticipate a process for making it.

1. The two patent citations actually on the face of 5510486

Both issued 15 months before the '486 filing date (1994‑07‑26), so both qualify as prior art under pre‑AIA § 102(b) (printed publication/patent more than one year before filing), and also as § 102(a)/(e) art. Common ownership by Syntex does not remove a § 102(b) reference.

Reference A — US 5,202,333 A

Description. A genus of "tricyclic 5‑HT₃ receptor antagonists containing a bridged bicyclic amine substituent." Formula I broadly embraces the palonosetron skeleton. Trial testimony in the Helsinn/Teva litigation confirmed that the '333 specification generically encompasses palonosetron, including the language "compounds of Formula I in which each p, q and u are 0, and R³ is 1‑azabicyclo[2.2.2]oct‑3‑yl, in particular wherein one or, when present, both chiral centers possess S configurations" (see Helsinn cert. petition excerpt, http://patentlyo.com/media/2018/03/Helsinn-cert-petition-17-xxx.pdf). The patent also discloses pharmaceutical compositions (Example 13 IV formulation), methods of use, intermediates, and "processes for preparation."

Anticipation assessment (§ 102). None of claims 1–8 are anticipated.

• The '486 specification itself distinguishes this reference: "Methods for using these 5‑HT₃ antagonists and certain processes for their preparation, different from those described herein, are described in U.S. Pat. No. 5,202,333."
• Claims 1, 4 and 7 each require the specific sequence: (A) coupling a naphthoyl‑L compound (Formula 5) with 1‑azabicyclo[2.2.2]oct‑3‑ylamine; (B) reducing the resulting carboxamide; and (C) reacting the resulting amine with a formylating agent and then a Lewis acid. The '333 patent is a compound/genus patent whose preparative routes (per the '486 text) do not include this arrangement of steps. A single reference must disclose all limitations — '333 does not.
• At most, '333 is § 103 obviousness art against the product, not § 102 art against the process claims. It cannot anticipate the process claims on the record retrieved.

Reference B — US 5,202,318 A

Description. Azabicyclobenzisoquinolines of Formula I in which Z is CH₂ or C=O, with X/Y substituents and R¹ selected from a set of amine groups that explicitly includes 1‑azabicyclo[2.2.2]oct‑3‑yl (see claim 3: "1‑azabicyclo[2.2.2]oct‑3‑yl; 1‑azabicyclo[2.2.2]oct‑4‑yl; ..."). It claims pharmaceutical compositions, methods of use, intermediates (Formulae IIIA/IIIB), and processes for preparation. Retrieved via FPO (https://www.freepatentsonline.com/[5202318](/patent/5202318).html) and Google Patents (https://patents.google.com/patent/[US5202318A](/patent/US5202318A)/en).

Anticipation assessment (§ 102). None of claims 1–8 are anticipated.

• The '318 genus overlaps in the quinuclidinyl‑benz[de]isoquinoline motif, but the claimed compounds are different species (e.g., the 1,3‑dione/CH₂ variants and substituted analogs, claim 5: 6‑amino‑2‑(1‑azabicyclo[2.2.2]oct‑3‑yl)‑2,3‑dihydro‑1H‑benz[de]isoquinoline‑1,3‑dione). It does not disclose the '486 four‑step process, nor the specific reactants (Formula 5 acid chloride + quinuclidin‑3‑amine), nor the formylation/Lewis‑acid cyclization, in the claimed arrangement.
• No § 102 anticipation of claims 1–8.

2. Non‑patent literature citation

Citation: Morrison & Boyd, Organic Chemistry, 3rd Ed., p. 756 (listed twice in the OCR of the "Non‑Patent Citations" field).

Date: The 3rd edition of Morrison & Boyd dates to 1973 — long before the 1994 filing. It therefore qualifies as § 102(b) prior art.

Description / anticipation assessment. This is a general organic‑chemistry textbook page cited by the examiner for a background transformation (most plausibly amide formation/reduction or an electrophilic aromatic substitution relevant to the cyclization). I cannot state with high confidence what specifically appears on p. 756, and I will not fabricate its content. Whatever it teaches, a single textbook page of generic chemistry cannot disclose the specific compounds and the ordered four‑step process of claims 1, 4 and 7, so it cannot anticipate any claim. It is at most evidence of the general knowledge of a skilled artisan (relevant to § 103, not § 102).

3. Family‑level / related references (not face citations)

4. Bottom line on § 102

No claim of US 5,510,486 (claims 1–8) is anticipated by any reference cited on its face, by the Morrison & Boyd NPL entry, or by the family‑level US 4,920,227.

• The two patent references (US 5,202,333 and US 5,202,318) are product/genus and use patents issued 1993‑04‑13; they are § 102(b) prior art as to date and disclose the quinuclidinyl‑benz[de]isoquinoline scaffold (including, generically, palonosetron in the '333 patent), but they do not disclose the claimed ordered process of (A) naphthoyl‑L + quinuclidin‑3‑amine coupling → (B) carboxamide reduction → (C) formylation + Lewis‑acid cyclization. The '333 reference is expressly characterized in the '486 specification as disclosing a different preparation.
• The Morrison & Boyd page is generic background chemistry; it cannot meet the "all elements in a single reference" test.
• These references therefore function as § 103 obviousness/background material, not § 102 anticipatory art.

5. Explicit uncertainties

1. US 5,202,333 preparative examples. I did not retrieve the full column‑by‑column experimental section of the '333 patent. My conclusion that it does not anticipate rests on (a) the '486 specification's own statement that the '333 processes are "different from those described herein," and (b) the absence of the specific step sequence in the retrieved portions. A column‑level read of '333's examples would be required to be fully certain no individual claimed step is disclosed there.
2. Morrison & Boyd p. 756 contents. Unknown to me with confidence; I have not asserted a specific teaching.
3. Face-citation completeness. The Google Patents OCR of the "Patent Citations (2)" and "Non‑Patent Citations (2)" fields matches the EveryPatent rendering (two U.S. patents + one NPL entry). I have treated US 4,920,227 as family‑level only, consistent with its location in the "Family Cites Families" field rather than "Patent Citations."
4. Date convention. The one‑day discrepancy between Google Patents/USPTO (filing 1994‑07‑26; issue 1996‑04‑23) and Unified Patents (priority 1994‑07‑25; grant 1996‑04‑22) noted in the earlier section persists; it does not affect any § 102 conclusion here, since both cited patents issued in April 1993 regardless.

Sources: https://patents.google.com/patent/US5510486/en ; http://www.everypatent.com/comp/pat5510486.html ; https://portal.unifiedpatents.com/patents/patent/US-5510486-A ; https://patents.google.com/patent/US5202333 ; https://patents.google.com/patent/US5202318A/en ; https://www.freepatentsonline.com/5202318.html.

I'll ground this analysis in the specific prior-art references listed on the patent page before constructing the § 103 argument.

Good grounding. Let me verify what the '333 reference actually teaches about making the compound, and check whether the '486 claims were ever challenged on § 103.

Obviousness Analysis — US 5,510,486 under 35 U.S.C. § 103

Cross-reference: bibliographic data, claim structure, and litigation posture are in the previously generated sections and are not repeated here. This memo assumes those facts. Note one internal inconsistency flagged below (§0).

0. Threshold flags before the analysis

1. Internal inconsistency in the patent itself (do not auto-correct). The abstract as printed reads "2‑(1‑azabicyclo[2.2.2]oct-3-yl)-2,3,3a,4,5,6-tetrahydro-1H-benz[de]isoquinolin-1-one," whereas the title and every claim recite "hexahydro." The claims control; the abstract appears to be an error. This does not change the §103 analysis but matters if anyone argues the abstract limits the disclosure.
2. Two of the three §102(b) references are the applicant's own earlier Syntex patents. This shapes the obviousness case (same assignee → same field, same problem, "continuing the same research program" motivation).
3. I could not retrieve the actual text of the '333 process examples, nor verify the exact content of Morrison & Boyd p. 756. Where I rely on those, I say so explicitly rather than treating it as established.

1. Analytical frame

The § 103 inquiry is Graham v. John Deere, 383 U.S. 1 (1966), as refined by KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007). The claims here are process claims to a method of making a known compound (palonosetron; disclosed in US 5,202,333, and marketed as Aloxi®). That matters: the novelty of the product is irrelevant, but neither does an old product automatically make a new process obvious — the combination of steps must be evaluated for what the art would have suggested. See MPEP § 2142, § 2144.04 (In re Best, 562 F.2d 1252).

The core question: on 26 July 1994, would a person of ordinary skill in the art (PHOSITA), faced with the known target compound and its known (but "different") synthesis, have had reason to arrive at the claimed route — (A) acid-chloride/amine coupling → amide; (B) amide reduction → secondary amine; (C) formylation + Lewis-acid cyclization → tricyclic lactam — with a reasonable expectation of success?

2. Level of ordinary skill

A synthetic/medicinal chemist with a Ph.D. (or M.S. plus several years, or B.S. plus substantial experience) in organic synthesis, familiar with the classical named transformations and functional-group interconversions routinely taught in a graduate organic text (Friedel–Crafts acylation, Bischler–Napieralski-type ring closure, acid-halide/amine amidation, hydride and borane reductions of amides). This is the level the record itself implies: the sole non-patent reference cited by the Examiner is a general organic chemistry textbook (Morrison & Boyd, 3d ed., p. 756), which is textbook-level evidence of ordinary skill, not of a specialist invention.

3. Scope and content of the prior art of record

Also on the face of the document: US 5,202,333 and US 5,202,318 are listed as the only two patent citations considered; US 4,920,227 is cited in the family.

4. Claim construction for §103 purposes

• Independent claims 1, 4, 7 are nested subsets of one route (full route / from the pre-made amide / from the pre-made amine). Claims 4 and 7 are simply the downstream halves; if any one is obvious, all three fail together unless a step-specific showing is made.
• Steps (D)/(E)/(F) [and their analogues in claims 4 and 7] are expressly optional. Under Ex parte practice and MPEP § 2111.02, an "optionally" step confers no weight when not performed. So the claims reduce to the mandatory transformations.
• The claims recite no reaction conditions, solvents, temperatures, reagents, or yields. That is significant: the nonobviousness arguments that depend on "critical" process parameters or narrow ranges are unavailable on the face of the claims (In re Aller, 220 F.2d 454 — discovering optimum or workable ranges by routine experimentation is not inventive). The only substantive limitations are the sequence of transformations and, in the dependents, the stereochemistry of the starting materials.

5. Claim-by-claim mapping

Combination I (primary): US 5,202,333 + US 5,202,318 + Morrison & Boyd

Result: every element is either expressly disclosed or is a conventional transformation for which the art supplied the reagents and the predictable outcome. On this record a prima facie case of obviousness is available against claims 1, 4 and 7, and derivatively against 2, 3, 5, 6 and 8.

Combination II (secondary, narrower): US 4,920,227 + Morrison & Boyd + US 5,202,333

• '4920227 supplies the amide motif and its preparation (step A); Morrison & Boyd supplies the reduction (B) and the acylation cyclization (C); '333 supplies the specific target. This combination is weaker than Combination I because '4920227 is not directed to the fused benz[de]isoquinolinone ring — its compounds are benzobicyclic carboxamides that are not cyclized. It is better used to corroborate step (A) than as the primary teaching of the ring-closure.

Combination III: US 5,202,318 + Morrison & Boyd (steps B and C only) — directed at claims 4 and 7

• For claim 7, the only mandatory step is formylation + Lewis acid. '318 discloses the tricyclic lactam (Z=C=O) of the same ring system and states that the invention includes "processes for preparation." Morrison & Boyd supplies the classic N-acyl/Lewis-acid ring closure (the Bischler–Napieralski/Friedel–Crafts analogy). This is the strongest single-combination attack because the claim is the narrowest.
• For claim 4, '318 + Morrison & Boyd covers reduction and cyclization; the amine starting material is the reduced form of a compound disclosed in '318.

6. Motivation to combine (KSR rationales)

1. Known, identified, desirable target. Palonosetron was already disclosed and claimed in '333 and singled out (S,S stereochemistry) as preferred. One does not "invent" a new use for the compound; the task is to make it better. KSR recognizes that "if a technique has been used to improve one device [here, compound synthesis], and a person of ordinary skill … would recognize that it would improve similar devices in the same way, using the technique is obvious."
2. Finite number of identified, predictable solutions. The synthetic toolkit for converting a 1‑arylethylamine into a fused lactam — amidate the nitrogen, then cyclize onto the aromatic ring with a Lewis acid (the Bischler–Napieralski/intramolecular Friedel–Crafts family) — was a small, well-mapped set. "When there … [is] a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options." KSR, 550 U.S. at 421.
3. "Obvious to try" with a reasonable expectation of success. Each individual step is a high-reliability, textbook transformation with predictable outcomes; a PHOSITA would have a reasonable expectation that the sequence would deliver the known lactam.
4. Same field, same problem, same assignee. '333 and '318 are Syntex patents by the same research group (Berger/Clark et al.) that produced the compound; the '486 is a process improvement by a different Syntex team (Robinson/Rohloff/Kowalczyk). Common ownership and a continuous research program strengthen the motivation and the "reasonable expectation of success." See MPEP § 2144.03 (common assignee).
5. Development pressure / "better process" as a recognized problem type. Syntex had filed an IND (1992) and was running dose-ranging Phase II studies (Study 2330 began May 1994). The commercial need for a scaleable, stereochemically faithful synthesis of a compound already identified as a drug candidate is precisely the kind of practical problem the art was addressing.

7. Counterarguments, and how they fare

For nonobviousness (patent owner):

• "Different from those described herein." The '486 specification expressly acknowledges that '333 describes processes for the same compound that are different. Where the closest art teaches the compound but a different route, the applicant can argue the art pointed away from the claimed sequence — i.e., no suggestion to select the amide→amine→acylative-cyclization ordering. This is the strongest argument, and it is a genuine one: "a different process" is not the same as "an obvious alternative," especially where the art did not identify the specific intermediates.
• Unexpected result at step (C). The claimed formylation/Lewis-acid step is asserted (Ex. 6) to deliver the hexahydro (saturated) lactam directly with high yield and no racemization (64.41 g, [α]D 90°, m.p. 303 °C dec.). If the art's known route to this skeleton proceeds via the tetrahydro (unsaturated) lactam, and required a separate hydrogenation to reach the hexahydro form, then eliminating that step and retaining stereochemical integrity could be argued as unexpected. Whether it is unexpected is a factual question that would require the '333 examples — which I have not been able to read. Flagged as the pivotal unresolved fact.
• Diastereomeric upgrade by crystallization. Example 4 upgrades an 82:18 (S,S):(S,R) mixture to 92.5% purity by repeated toluene crystallization. The owner could argue an unexpected purification advantage. Against this: "purification by recrystallization" and "optimization of resolution conditions" are routine (In re Aller; MPEP § 2144.05), and the claims do not recite the crystallization.
• Secondary considerations — commercial success / copying. Aloxi® was a commercial success, and later generics filed process patents citing the '486 (e.g., CN 1,013,145, which discusses recrystallizing palonosetron HCl "per the process of U.S. Patent No. 5,510,486," among the 22 documents citing the '486). But the nexus is weak: the commercial success is overwhelmingly attributable to the compound's pharmacology (the '333 compound patent and the later formulation patents), not to the '486 process. Copying evidence is likewise diluted because the '486 route is simply the practical route to a drug the generics had to make for other reasons.

For obviousness (challenger):

• The claims recite only the transformations, not reagents, conditions, or yields. This forecloses "critical parameter" arguments and leaves only the sequence — which is the classical retrosynthetic path once you accept the intermediates.
• The two express teachings in the same-assignee patents (the S,S target in '333; the C=O/CH₂ pairing in '318) supply both the goal and the key structural insight (that the lactam is obtainable from the amine).
• The record's only non-patent reference is a general textbook, signalling that the Examiner viewed the chemistry as routine.

8. Bottom line

• On the record as it stands, a prima facie § 103 case is available against all eight claims, strongest against independent claims 4 and 7 (the downstream, narrower halves) via US 5,202,318 + Morrison & Boyd p. 756, and against claim 1 via US 5,202,333 + US 5,202,318 + Morrison & Boyd, with US 4,920,227 corroborating the amide-forming step. The dependent stereochemistry claims (2, 3, 5, 6, 8) are supported by the '333 specification's express preference for the S,S configuration plus routine optical resolution.
• The case is not a slam dunk. The single most important gap is that the '333 reference describes a different process, and I could not read '333's examples or Morrison & Boyd p. 756 to determine (a) whether the recited sequence was itself disclosed or suggested, and (b) whether the direct, stereoretentive hexahydro cyclization was an unexpected result. A real validity opinion needs the full text of '333 (especially Example 11 and its "processes for preparation") and the actual page 756.
• Anticipation (§102) is a separate question and probably negative on the express statement in the '486 spec that '333's processes are different — but that, too, depends on '333's actual examples. If '333's disclosed process turns out to be the same four steps, claims 1/4/7 would be anticipated outright; that would be a §102(b) problem, not merely a §103 one.

Explicit uncertainties

1. '333 example text unavailable to me. The '333 process for making the compound (referred to by the '486 as "different") is the decisive document and I have not read it. The Colombian office action and the Teva/Helsinn briefing establish that '333 discloses palonosetron (Ex. 11; claims 31/32) and the S,S preference (col. 9, ll. 23–26), but not what its synthesis steps are.
2. Morrison & Boyd p. 756 content unverified. I have treated it as general-skill evidence; I cannot state what specific transformation it depicts.
3. No prosecution-history review. I have not examined the '486 file wrapper; whether the Examiner made or withdrew a §103 rejection over '333/'318 is unknown.
4. No litigation/PTAB §103 ruling on the '486 located (consistent with the previously generated sections). This memo is an independent analyst's assessment, not a determination.

Sources cited

• US 5,510,486 A — https://patents.google.com/patent/[US5510486A](/patent/US5510486A)/en
• US 5,202,333 A — https://patents.google.com/patent/US5202333 (spec excerpts quoted in the Teva Supreme Court briefing and petition, https://patentlyo.com/media/2016/03/TevaSecretSaleBrief.pdf and http://patentlyo.com/media/2018/03/Helsinn-cert-petition-17-xxx.pdf; '333 Ex. 11 identified as palonosetron in Colombian Office Action, https://veraabogados.com/wp-content/uploads/2025/08/08134323.pdf)
• US 5,202,318 A — https://patents.google.com/patent/[US5202318A](/patent/US5202318A)/en
• US 4,920,227 — https://patentimages.storage.googleapis.com/ec/9e/25/ad32344c2bfc25/US4920227.pdf
• Palonosetron preparation note (listing US 5,202,333 as the preparation reference and B. A. Kowalczyk, Heterocycles 43, 1439 (1996) as the "improved synthesis") — https://www.drugfuture.com/chemdata/palonosetron.html
• CN 101157691 B (states US 5,202,333 is the earliest-reported palonosetron synthesis) — https://patentimages.storage.googleapis.com/f8/be/91/077f065059d5a8/CN101157691B.pdf