US 6806370

I'll search for authoritative information on this specific patent number.

Let me search specifically for any CAFC 2026 activity or litigation involving this patent.

Search results summary — US Patent No. 6,806,370

Searches run: the specific number 6806370 (as "US6806370B2", "US 6,806,370"), plus a targeted query for CAFC 2026 appellate activity. All patent-number hits returned were for 6806370 itself — no results for similar/neighboring numbers were returned, so nothing below is contaminated by a look-alike patent.

Bibliographic data (corroborated by Google Patents, FreePatentsOnline, and PubChem patent record)

Family/continuity: This patent is a divisional of US 10/337,543 (issued as US 6,747,026), which is itself a divisional of US 09/904,059 (issued as US 6,593,472). A sibling divisional, US 10/616,276, issued as US 6,897,226. The underlying disclosure (the "parent compounds" of formula II) is described as being preparable per EP 1,035,115.

Sources: https://patents.google.com/patent/US6806370/en ; https://www.freepatentsonline.com/6806370.html ; https://pubchem.ncbi.nlm.nih.gov/patent/US-6806370-B2

Plain-language overview of the claims (13 claims total)

The claims are directed to N-oxide ("amine oxide") derivatives of 4-phenyl-pyridine NK-1 antagonists — i.e., the oxidized-amine form of a known drug class, designed to be a prodrug that reverts to the active parent (formula II) in the body (the spec attributes reduction to a mechanism likely catalyzed by hemoglobin). The stated problem solved is poor water solubility of the parents, which blocks bolus/parenteral injection.

Independent Claim 1 (the broad structural claim). A compound (or its pharmaceutically acceptable acid-addition salt) based on a pyridine ring carrying a substituted phenyl group and an amide/amine substituent, with the ring nitrogen oxidized (the N-oxide). Variable definitions:

• R = H, lower alkyl, lower alkoxy, halogen, or trifluoromethyl; R¹ = H or halogen; or R and R¹ taken together (adjacent) form —CH═CH—CH═CH— (a fused benzo/naphtho-type bridge).
• R², R²′ = H, halogen, CF₃, lower alkoxy, or cyano; or, when adjacent, together form —CH═CH—CH═CH—, optionally substituted by one or two lower alkyl or lower alkoxy groups.
• R³, R³′ = H, lower alkyl, or cycloalkyl.
• Key structural limitation: R⁴ and R⁴′ together with the nitrogen to which they are attached form a 5-membered nitrogen-containing heterocyclic ring (e.g., pyrrolidinyl), which may have 0 or 1 additional heteroatom (S, N, O) — and if sulfur is present it must be in sulfonyl form.
• R⁵ = H, hydroxy, lower alkyl, lower alkoxy, —(CH₂)ₘOH, —COOR³, —CON(R³)₂, —N(R³)CO-lower alkyl, or —C(O)R³; R⁶ = lower alkyl; X = —C(O)N(R⁶)—, —N(R⁶)C(O)—, —(CH₂)ₘO—, or —O(CH₂)ₘ—; n = 0–4; m = 1–3.

Note the narrow claiming strategy versus the specification: the specification's formula I permits R⁴/R⁴′ to be a 5- or 6-membered ring and R⁶ to be H/lower alkyl/phenyl; claim 1 is limited to the 5-membered ring and R⁶ = lower alkyl, and omits the 6-membered (morpholine/piperidine) embodiments. That is why morpholine-containing species (e.g., the Example 1 and 16 compounds) do not read on claim 1 as issued.

Claims 2–4 depend from claim 1 and narrow R = methyl (2), R = chloro (3), or R²/R²′ fused to form —CH═CH—CH═CH— (4).

Claim 13 (the other independent claim — a single-compound claim). The specific compound (RS)-6-[3-(acetyl-methyl-amino)-1-oxo-pyrrolidin-1-yl]-N-(3,5-bis-trifluoromethyl-benzyl)-N-methyl-4-o-tolyl-nicotinamide — i.e., the pyrrolidine-N-oxide species named in the specification as Example 15.

Claims 5–8 and 9–12 are formatted as "The compound of claim 1 having the structure [formula]," i.e., structurally they are dependent claims (each incorporates claim 1) that narrow to particular sub-genera shown only as chemical structures in the patent text; claims 6–8 and 10–12 apply the same methyl / chloro / fused-naphtho limitations to those sub-genera. Because these claims explicitly recite "of claim 1," the only strictly independent claims are claim 1 and claim 13, notwithstanding that claims 5 and 9 serve as structural sub-genus anchors. (The patent's own Summary section refers to "compounds of formula Ic/Id/Ie," which correspond to these sub-genera.)

Source for claim text: https://patents.google.com/patent/US6806370/en (Claims 1–13)

CAFC / USPTO docket check — with an explicit caveat

• I found no Federal Circuit (CAFC) 2026 docket entry, appeal, or decision naming US 6,806,370. My targeted query for CAFC-2026 activity on this number returned zero results.
• The absence is consistent with the patent record: Google Patents shows the patent as "Expired – Lifetime," anticipated expiration 2021-07-12. A patent that lapsed in 2021 would not ordinarily be the patents-in-suit in a live 2026 appeal.
• Related but distinct litigation that did surface (do not attribute to 6806370): current NK-1/netupitant disputes involve Helsinn and patents such as US 10,828,297 and US 10,828,297-family/'698, '450, '586 etc. (ANDA litigation involving Gland Pharma, D.N.J.; and IPRs filed by Azurity Pharmaceuticals). US 6,806,370 appears in those records only as a cited/background reference (e.g., cited in an EP prosecution document alongside US 6,593,472 and US 6,747,026). See e.g. https://ptacts.uspto.gov/ptacts/public-informations/petitions/[1557835](/patent/1557835)/ and https://storage.courtlistener.com/recap/gov.uscourts.njd.[499051](/patent/499051)/gov.uscourts.njd.499051.1.1.pdf

Uncertainty statement: I have not verified the USPTO PatentCenter/Assignment record or the CAFC docket directly (only web-indexed sources), so I cannot rule out a dormant or recently-docketed matter that isn't yet indexed. Based on all indexed results, however, there is no CAFC 2026 proceeding for US 6,806,370, and any authority asserting the contrary should be independently verified against PACER/CAFC and USPTO PatentCenter. I also have not confirmed a specific commercial drug mapping for this patent (e.g., whether any marketed product practices its claims); the search results link the surrounding family to the netupitant/NK-1 field, but I did not find an authoritative source tying US 6,806,370's claims to a named marketed product.

I'll search for litigation involving US patent 6806370 across patent litigation databases.

Let me search more specifically on litigation databases.

Let me search more targeted litigation sources for this specific patent.

Litigation Search: U.S. Patent No. 6,806,370

Bottom line: I found no evidence of any litigation (district court or Federal Circuit) that specifically names U.S. Patent No. 6,806,370 as an asserted patent. I want to be explicit that this is a negative finding based on the searches I was able to run, not a positive confirmation of a litigation-free history — a formal PACER/Lex Machina/Docket Navigator query billed by patent number would be needed for a definitive answer.

What the patent is (context for why it likely was never asserted)

• Patent: U.S. 6,806,370 B2, "NK-1 receptor active amine oxide prodrugs"
• Assignee: Hoffmann-La Roche Inc. (original and current per Google Patents/PubChem)
• Inventors: Torsten D. Hoffmann, Sonia Maria Poli, Patrick Schnider, Andrew Sleight
• Priority: 2000-07-14 (EP 00115287); Filed (as-applied): 2003-08-21; Granted: 2004-10-19
• Family: Divisor/continuation of US 09/904,059 (now US 6,593,472), US 10/337,543 (now US 6,747,026), and sibling US 10/616,276 (now US 6,897,226) — all "NK-1 receptor active amine oxide prodrugs." Corresponding family members include EP 1303490 B1, JP 3950044 B2, KR 100501608 B1, CN 1178917 C, etc.
• Status: Expired – Lifetime; Google Patents lists an "anticipated expiration" of 2021-07-12.
• Claims: 13 claims directed to N-oxide (amine-oxide) prodrugs, including claim 13 to (RS)-6-[3-(acetyl-methyl-amino)-1-oxo-pyrrolidin-1-yl]-N-(3,5-bis-trifluoromethyl-benzyl)-N-methyl-4-o-tolyl-nicotinamide.

This is a prodrug patent covering N-oxide derivatives of Roche's 4-phenyl-pyridine NK-1 antagonists. The commercially relevant molecule family here is netupitant (the parent drug, whose Roche compound patents are in the same citation tree, e.g., EP 1103545 B1, US 6,297,375). The marketed prodrug that eventually reached the clinic — fosnetupitant (in Akynzeo® for Injection, Helsinn) — is a phosphate/phosphonooxymethyl-type prodrug, chemically distinct from the amine-oxide prodrugs claimed in the '370 patent. That distinction is consistent with the '370 patent apparently never being asserted.

What the litigation searches did return (none involving '370)

My searches surfaced active NK-1/netupitant litigation, but every case involved different patent numbers, not '370:

None of these pleadings or PTAB papers reference U.S. 6,806,370.

Caveats and how to confirm

1. No matches ≠ no litigation. My queries (Unified Patents/docketalarm caselist material, DrugPatentWatch-style listings, general web searches keyed to "6,806,370"/"6806370") did not produce a case naming this patent. A patent that expired in 2021 and claims a never-commercialized prodrug form is a plausible candidate for never having been asserted.
2. Search limitation. I could not complete a query with the tool step budget for drugpatentwatch, Docket Alarm, or PACER directly by patent number. If you need a formal clearance, run the following:
   • Docket Navigator / Lex Machina: filter "Patent Number = 6,806,370" under Litigation and PTAB.
   • Unified Patents Portal (https://portal.unifiedpatents.com/litigation) and its "Patent Litigation" search.
   • PACER / CourtListener RECAP: full-text search of "6,806,370" and "6806370."
   • USPTO Patent Center / Assignment for any reissue, reexam, or transfer that could create litigation posture.
3. Conflicting-result rule. Had any search returned a case naming 6,806,370, I would have prioritized it; none did, so I am reporting the negative finding rather than inferring litigation from the related netupitant cases.

Conclusion: Based on the searches performed, no known litigation appears to involve U.S. Patent No. 6,806,370. The NK-1/netupitant litigation that does exist (Helsinn v. Gland, Helsinn v. Teva, and the 2025 Azurity IPRs) concerns different patents in the netupitant/palonosetron space and should not be attributed to '370.

I'll verify the structured data with targeted searches before writing.

Let me run additional targeted searches to confirm the absence or presence of proceedings.

PTAB Proceedings Analysis — US 6,806,370 B2

Patent: US 6,806,370 B2 ("NK-1 receptor active amine oxide prodrugs")
Patent Owner: Hoffmann-La Roche Inc. (original assignee)
Priority date: 2000-07-14 | Granted: 2004-10-19 | Status per Google Patents: Expired – Lifetime (anticipated expiration 2021-07-12)
Source of record: USPTO Open Data Portal structured block ("PTAB proceedings on file") supplied with this prompt.

Proceedings overview

There are zero AIA trial proceedings on file against US 6,806,370 — no IPRs, no PGRs, no CBMs, no institution denials, and no settlements; the breakdown is 0 active / 0 claims invalidated / 0 claims sustained / 0 settled / 0 institution-denied. That absence is not a "hardened patent" story, however: the disposition that actually matters for a defendant is that the patent itself expired on 2021-07-12 (20 years from the 2001-07-12 filing date of parent application 09/904,059), so the relevant defensive posture is "the '370 patent is off the board entirely — a demand letter citing it cannot support prospective infringement, and the pre-expiration damages window has closed."

Proceedings

None on file.

The canonical structured source (USPTO ODP) returns no AIA trial proceedings for this patent, and my independent web searches did not surface any IPR/PGR/CBM referencing US 6,806,370, nor any Federal Circuit appeal of an FWD on this patent. Specifically, I searched for proceedings tied to the patent number and to the Hoffmann-La Roche / Helsinn netupitant patent family and found no petition, institution decision, FWD, or appeal naming this patent.

Important adjacent-signal caveat (do not confuse these with '370). Web search did surface live PTAB materials involving Helsinn's separate netupitant-family patents — e.g., an Azurity Pharmaceuticals petition/record discussing a Helsinn "'357 patent" whose claim 4 recites blood levels of palonosetron and netupitant, and N-oxide/phosphate-prodrug chemistry discussions tied to fosnetupitant (PTACTS petition record). Those hits are on different patents with different claims than US 6,806,370, and I could not confirm a proceeding number from the search results, so I am not attributing any proceeding to '370. The other two PTACTS hits returned by search (Woodway curved-treadmill IPR) are unrelated.

• Type: n/a — no proceeding
• Filed: n/a
• Status: No AIA trial activity (verbatim: ODP returns no proceedings)
• Judge panel: n/a
• Petition grounds: n/a
• Institution decision: n/a
• Final Written Decision: n/a — no claim of US 6,806,370 has ever been canceled or upheld by the PTAB
• Settlement / termination: n/a
• Appeal: none found
• Defensive value: You cannot point a court or a demand-letter sender to an FWD cancelling claims here — but you don't need to. The patent is expired, so the better move is to attack the assertion on the merits of enforceability/enforceable term, not on PTAB record.

Strategic summary

Claim status — CANCELED vs. SUSTAINED vs. UNTESTED. No PTAB has touched this patent, so its 13 claims stand exactly as issued: claim 1 (genus of NK-1 N-oxides), claims 2–4 (R = methyl; R = chloro; R²/R²′ naphtho-fused bridge), claims 5–8 (a first sub-genus with R, R²/R²′, R³/R³′), claims 9–12 (a second sub-genus including R⁴/R⁴′ heterocycle variants), and claim 13 (the single species (RS)-6-[3-(acetyl-methyl-amino)-1-oxo-pyrrolidin-1-yl]-N-(3,5-bis-trifluoromethyl-benzyl)-N-methyl-4-o-tolyl-nicotinamide). None is canceled; none is adjudicated. Practically, the only live question is whether any pre-2021-07-12 damages remain recoverable — and per 35 U.S.C. § 286 the six-year lookback from a 2026-09-30 filing would reach back only to 2020-09-30, of which the patent's enforceable life covered roughly nine-and-a-half months. Verify the expiration date and any terminal disclaimer or PTA against USPTO Patent Center before relying on it, but on the face of the record this patent is dead.

Estoppel landscape. Because there is no instituted proceeding and no FWD, no § 315(e)(2) estoppel attaches to anyone — there is no petitioner, real party in interest, or privy barred from raising § 102/§ 103 grounds in district court or the ITC. Conversely, that means there is also no PTAB record a defendant can borrow: no claim-construction ruling, no invalidity finding, no expert record. Any validity challenge today would have to be built from scratch in the district court under the clear-and-conviction standard.

Pattern signals. There is no repeat petitioner, no serial-filing pattern, and no defensive aggregator (Unified Patents or similar) in the chain — the patent's whole family (US 6,593,472, US 6,747,026, US 6,897,226, and '370) shows no PTAB activity of which I am aware. The commercial explanation is straightforward and is an inference, not a record finding: netupitant's actual commercial intravenous prodrug, fosnetupitant, is a phosphate ester, not an N-oxide, so the '370 N-oxide genus is largely off the commercial critical path. That, plus expiration, explains why no challenger ever spent $500K on a petition.

Recommended next steps

1. Lead with expiration, not invalidity. US 6,806,370 (and its siblings US 6,593,472, US 6,747,026, US 6,897,226) expired 2021-07-12. Confirm on USPTO Patent Center that maintenance fees lapsed/were not revived and that no term extension changes the date. If confirmed, a demand letter citing '370 supports no prospective infringement claim.
2. Demand the exact patent and claim. If a threat letter cites the netupitant family, identify which patent: the compound itself is claimed elsewhere (e.g., US 6,297,375, also long expired), while '370 covers only N-oxide prodrugs. There is no FWD to link to and quote — say so plainly rather than implying one exists.
3. Check the § 286 window. Any damages theory premised on '370 is limited to acts within six years of suit and, more tightly, to acts before 2021-07-12. Run that arithmetic before engaging on the merits.
4. Do not expect PTAB help. With the patent expired, an IPR is of marginal utility (and the Board's practice on expired patents complicates claim construction); the cost-effective path is a Rule 12 motion or summary judgment on expiration/standing-to-recover, not a petition.
5. Monitor for revival or family-wide assertions. If Roche/Helsinn or a successor ever asserts the broader netupitant portfolio, the USPTO PTAB E2E system and the PTAB Decisions page are the places to re-check whether new proceedings appear — the ODP data can lag recent filings.

Confidence note: High confidence that no PTAB proceeding exists on '370 as of the ODP ingest; moderate confidence that none exists anywhere, since I could not access the full PTACTS docket for confirmation and search engines index PTAB records imperfectly. I have deliberately not assigned any proceeding number to this patent.

I'll research the assignment record for this patent across the sources you named.

Let me dig into the assignment-specific sources and the family's legal events.

Let me try to reach the Assignment Center records directly and check the family's chain of title.

Access caveat, stated up front: I was unable to execute a live query against USPTO Assignment Center (https://assignmentcenter.uspto.gov/) or the legacy https://assignment.uspto.gov/patent/index.html in this session — no assignment-record page for US 6,806,370 was retrievable, and no search result surfaced a reel/frame, conveyance type, or assignment correspondent for this patent. Everything below is therefore built from bibliographic/assignee-of-record data (Google Patents, FreePatentsOnline, PubChem's patent record) and the statements already generated in the prior section. I did not find, and therefore will not invent, any reel/frame entry. Where a field is unknown I say so. A definitive chain-of-title answer requires a direct lookup at the Assignment Center link at the end of this memo.

Inventors

The citizenship data (DE / CH / CH / FR) comes from the PubChem patent record for US-6806370-B2; the patent itself does not separately list inventor residences in the fetched text. All four are consistent with a single Roche discovery group in Basel (the medicinal-chemistry/Biology pairing typical of an NK-1 program). The U.S. filing is in the name of Hoffmann-La Roche Inc., the Roche U.S. subsidiary, which is standard for a Basel-originated invention routed through the U.S. affiliate as applicant/assignee.

Unusual-pattern check: Nothing to flag. I found no evidence of inventors departing within 12 months of filing, and no inventor-held (unassigned) interest — the patent issued to a corporate assignee, not to individuals. Because I could not pull the assignment documents, I cannot independently confirm that all four executed inventor-to-Roche assignments; I state that as a gap, not as a finding. Note this is a 2000-priority pharma case — the inventor-to-corporate assignment is essentially certain in substance (employment/obligation-to-assign), but its recorded date and reel/frame are unverified here.

Original assignee

• Entity on the issued patent: Hoffmann-La Roche Inc. (the U.S. pharmaceutical subsidiary; address of record for correspondence on the patent face is Little Falls, NJ; Roche's U.S. pharma operations were historically headquartered in Nutley, NJ).
• Primary line of business: Branded prescription pharmaceuticals / CNS and oncology discovery. Roche is a large-cap operating company, not a holding or licensing vehicle.
• Did they ship a product embodying the claims? Unconfirmed — and probably not directly. The claims cover N-oxide prodrugs of the 4-phenyl-pyridine NK-1 parent compounds of "formula II." The specification frames the N-oxides as solubility-enabling prodrugs intended for parenteral administration; it does not identify a marketed product practicing the oxidized amine-oxide form. The prior section already flagged that no authoritative source ties US 6,806,370's claims to a named marketed product, and I did not improve on that here. Notably, the closest commercial NK-1 molecule in this chemical space (netupitant, Helsinn/Roche) is a piperazine analog, whereas the examples claimed/described here center on morpholine and small 5-membered cyclic amines — so I would not map this patent's claims onto netupitant without documentary support (the relevant Roche/Helsinn patent estate, e.g. US 6,297,375 and the EP 1,103,545 family, is a related but distinct family).
• Current status: Operating. Hoffmann-La Roche Inc. has not been dissolved and has not filed for bankruptcy. Roche restructured its U.S. footprint around 2013 (Nutley site wind-down, Genentech-centric U.S. integration), but that is a site/operations change, not a corporate dissolution that would trigger a patent fire-sale.

Assignment timeline

No recorded post-issuance assignment was found for US 6,806,370, and I could not retrieve the initial assignment record either. All indexed bibliographic sources are internally consistent and show:

• the application filed 2003-08-21 by Hoffmann-La Roche Inc. (Google Patents: "2003-08-21 Application filed by Hoffmann La Roche Inc → filed"),
• assignee listed as Hoffmann-La Roche Inc. by both the original and current-assignee fields (Google Patents), and as HOFFMANN LA ROCHE (US) by PubChem,
• no "Assigned to" / change-of-name / security-interest event in any source I could reach.

The only "correspondent"-type datum available is the prosecution correspondent on the patent face: "Attorney, Agent, or Firm: Hoffmann-La Roche Inc. (Little Falls, NJ, US)" — i.e., the applicant prosecuted in-house, with no outside firm of record. That is characteristic of a large corporate pharma patent department and is the opposite of the anonymous-shell/NPE correspondent pattern; but it is a prosecution artifact, not an assignment-record correspondent, so I do not treat it as a chain-of-title entry.

Per the rules: the Assignment Center returned no records I could verify for this patent. Taken at face value, that is the standard outcome for an operating-company-originated pharma patent — the original assignee (Hoffmann-La Roche Inc.) still holds title, and no NPE transfer ever occurred. I am flagging the residual uncertainty (inability to directly open the record) rather than presenting the negative as verified.

Timeline diagram

timeline
    title Ownership of US 6806370
    2000 : Priority EP 00115287 filed
    2001 : Grandparent US 09 904 059 filed
    2003 : Divisional US 10 645 895 filed
         : Applicant of record Hoffmann La Roche Inc
    2004 : Patent issued to Hoffmann La Roche Inc
    2021 : Anticipated expiration
         : No post issuance assignment found

NPE / troll-pattern signals

Verdict

Insufficient data — with a strong practical lean toward original operating-company ownership, never asserted.

Justification: I could not open a single USPTO Assignment Center record for US 6,806,370 (no reel/frame, no conveyance, no correspondent obtainable), so under your rule the only defensible verdict is Insufficient data (no records, or only the original assignment). Every bibliographic source that did resolve — Google Patents, FreePatentsOnline, PubChem — shows Hoffmann-La Roche Inc. as both original and current assignee, with no post-issuance transfer and no litigation naming the patent (consistent with the prior section's finding of no CAFC 2026 activity and a 2021-07-12 expiration). Operationally this reads as a classic big-pharma internal prosecution that was never sold and never asserted, i.e., the absence of an NPE chain is itself the finding — but that conclusion rests on the absence of records rather than on a verified chain, so I stop short of an affirmative "operating-company assertion" or "defensive/non-asserting" call (no products confirmed, no defensive aggregator confirmed).

Verify directly at: https://assignmentcenter.uspto.gov/ (search by patent number 6806370; also try application 10/645,895, and the family members 09/904,059, 10/337,543, 10/616,276, since a family-wide assignment would be recorded against the parents). Legacy interface: https://assignment.uspto.gov/patent/index.html. If you can retrieve the initial inventor→Hoffmann-La Roche Inc. reel/frame, that would convert this from "Insufficient data" to a clean "operating-company, retained title, no NPE activity" finding — I'd want the reel/frame in hand before asserting it.

I'll research the prior art citations for US 6,806,370. Let me search for the key references.

Let me research the remaining citations.

Let me verify the N-oxide disclosure in the Merck prodrug reference and check the two unusual EP citations.

Prior-Art Analysis — US 6,806,370 B2 ("NK-1 receptor active amine oxide prodrugs")

Method note / scope. I worked from the authoritative patent text you supplied (the Google Patents "Citations (8)" / "Patent Citations (9)" lists) and ran targeted searches on each cited reference. Patent identifiers are quoted literally as they appear; I did not auto-correct any number. Where the search results were thin, I say so rather than guess.

Up-front §102 conclusion. None of the cited references discloses an amine-oxide (N-oxide) of a 4-phenyl-pyridine bearing a 5-membered cyclic amine, and none discloses the specific claim-13 pyrrolidine N-oxide. Because the point of novelty of every claim (1–13) is the amine-oxide functionality on the cyclic tertiary amine, no cited reference literally anticipates any claim under 35 U.S.C. § 102. The references instead fall into four buckets: (a) the non-oxidized parent genus/compounds (US 6,297,375; WO 95/16679; WO 95/18124), (b) an N-oxide-prodrug teaching for a different ring size (WO 95/23798 ↔ US 5,691,336 — the strongest § 103 reference), (c) structurally unrelated pyridines (WO 98/04528), and (d) method-of-use / non-analogous art (US 5,972,938 and the two EP documents). Details below.

The eight cited references

1. EP 0 035 115 A1 — "Electronic musical instrument with performance mode selection"

• Assignee: Nippon Gakki Seizo Kabushiki Kaisha. Published 1981-09-09; priority 1980-01-28.
• Description: Consumer electronics / electronic musical instrument (organ) patent. No chemistry, no pharmacology.
• §102 relevance: None. Not analogous art (different field of invention); cannot anticipate any of claims 1–13. This entry appears to be a citation-extraction artifact or an irrelevant examiner reference — it should be treated as non-substantive. (I flag this rather than assume it belongs.)

2. EP 0 103 545 A2 — "Electrode for arc furnaces"

• Assignee: Arc Technologies Systems, Ltd. Published 1984-03-21; priority 1982-09-13.
• Description: Metallurgy / furnace-electrode technology.
• §102 relevance: None. Non-analogous art; cannot anticipate any claim. Same artifact caveat as #1.

3. WO 95/16679 A1 — "Morpholine and thiomorpholine tachykinin receptor antagonists"

• Assignee: Merck & Co., Inc. Prio. 1993-12-17 (US 169,889); pub. 1995-06-22. (Corresponds to EP 0 734 381 B1 and US 5,719,147.)
• Description: Substituted heterocycles — specifically morpholine/thiomorpholine 4-aryl-pyridine NK-1 (substance-P) antagonists; disclosed for inflammatory disease, pain, migraine, asthma, emesis. This is the origin of the parent compound class (formula II) whose N-oxides are claimed here.
• §102 relevance: None literally. It discloses the non-oxidized parent compounds (6-membered morpholine ring), not the N-oxides; and its ring system is 6-membered, whereas claim 1 requires a 5-membered ring. Potentially relevant only as background/generic §103 art on the "4-phenyl-pyridine NK-1 antagonist" scaffold. Cannot anticipate claims 1–13. Source: https://patents.google.com/patent/WO1995016679A1/en

4. WO 95/18124 A1 — "Substituted morpholine derivatives and their use as therapeutic agents"

• Assignee: Merck Sharp & Dohme Ltd. Prio. GB 9326480, 1993-12-29. (Corresponds to EP 0 737 192 B1.)
• Description: Aromatic compounds containing an amine-substituted azo-heterocyclic moiety; substituted morpholine derivatives as NK-1 (tachykinin) antagonists.
• §102 relevance: None literally. Again a 6-membered morpholine genus without the N-oxide; claim 1's 5-membered-ring limitation and the amine-oxide limitation are both absent. Background §103 art only.

5. WO 95/23798 A1 — "Prodrugs of morpholine tachykinin receptor antagonists" ⭐ most relevant

• Assignee: Merck & Co., Inc. Inventors: Dorn, Hale, MacCoss, Mills. Priority US 08/206,771 filed 1994-03-04. Its US counterpart is US 5,691,336 ("Morpholine compounds are prodrugs useful as tachykinin receptor antagonists").
• Description: This is the reference your patent's own Background expressly identifies: "N-oxides, described for example in U.S. Pat. No. 5,691,336." It teaches the use of N-oxide (amine-oxide) prodrugs of morpholine-based tachykinin/NK-1 antagonists to improve delivery/solubility — i.e., the same prodrug strategy that US 6,806,370 claims (oxidation of the cyclic tertiary amine → water-soluble N-oxide that is reduced back in vivo).
• §102 relevance: No literal anticipation, but this is the lead §103 reference. The disclosure is directed to the morpholine (6-membered) N-oxide, whereas:
  • Claim 1 expressly requires R⁴/R⁴′ to form a 5-membered nitrogen-containing ring (pyrrolidine-type) and R⁶ = lower alkyl; and
  • Claim 13 is a single pyrrolidine-ring N-oxide species.
    A 6-membered morpholine N-oxide does not meet the 5-membered-ring element, so it cannot §102-anticipate claims 1–13 on the face of the record. It would, however, be the reference a challenger would lead with for §103 (obviousness of extending the known N-oxide-prodrug approach to the 5-membered analogues), especially since the specification itself concedes N-oxide prodrugs are "well-known" and cites US 5,691,336.
• Confidence caveat: I confirmed the titles, inventors, assignee, and the specification's own characterization of US 5,691,336 as an N-oxide teaching, but I could not (search budget exhausted) verify whether this reference also enumerates pyrrolidine N-oxides rather than morpholine-only. If it does list 5-membered-ring N-oxides, the §102 picture for claims 1–12 would change materially and should be re-checked against the full WO 95/23798 / US 5,691,336 text.

6. WO 98/04528 A2 — "Substituted pyridines and biphenyls as anti-hypercholesterinemic, anti-hyperlipoproteinemic and anti-hyperglycemic agents"

• Assignee: Bayer Corporation. Prio. 1996-07-31; pub. 1998-02-05.
• Description: Substituted pyridines/benzenes as glucagon-receptor inhibitors and CETP inhibitors for diabetes/dyslipidemia (formulae IA/IB/IC/ID). Chemically it is a pyridine-containing biaryl class, but with a wholly different substitution pattern and a metabolic/endocrine utility.
• §102 relevance: None. Different structural genus (no NK-1 pharmacophore, no N-oxide, no 5-membered cyclic-amine N-oxide) and non-analogous utility. Cannot anticipate any claim; marginal §103 value at best.

7. US 5,972,938 — "Method for treating or preventing psychoimmunological disorders"

• Assignee: Merck & Co., Inc. Prio. 1997-12-01; grant 1999-10-26.
• Description: A method-of-treatment claim directed to administering a tachykinin (NK-1)-receptor antagonist to treat psychosomatic/psychoimmunologic disorders. It is cited in the present specification only for its therapeutic-utility teaching.
• §102 relevance: None. A method-of-use patent that does not disclose the N-oxide compounds of claims 1 or 13 (or any compound genus meeting them). It cannot anticipate a compound claim.

8. US 6,297,375 B1 — "4-phenyl-pyridine derivatives"

• Assignee: Hoffmann-La Roche Inc. Prio. 1999-02-24 (EP 99103504); filed 2000-02-22; granted 2001-10-02. This is the US counterpart of EP 1,035,115 A1 — the very document the specification names as the source for preparing the "parent compounds of formula II."
• Description: The genus of 4-phenyl-pyridine NK-1 antagonists (formula II type) — the non-oxidized compounds from which the claimed N-oxides are made (cf. the Example 1/16 parent compounds).
• §102 relevance: None literally, but it is the closest structural genus. It discloses the parent (un-oxidized) pyridines, whereas every claim requires the ring nitrogen to be oxidized (the amine oxide). Under §102 a reference must disclose all claimed elements arranged as in the claim; the N-oxide is missing. It is, however, the key §103 starting point (a known, same-assignee compound class + a known N-oxide-prodrug strategy from WO 95/23798). Source: https://patents.google.com/patent/[US6297375B1](/patent/US6297375B1)/en

Per-claim §102 bottom line

Two things I want to flag explicitly

1. No reference is anticipatory under §102; the real contest is §103. The single most material citation is WO 95/23798 A1 / US 5,691,336 (Merck / Dorn et al.), because it teaches N-oxide prodrugs of NK-1 antagonists. The distinction that keeps US 6,806,370's claims alive is the ring-size limitation (5-membered vs. the reference's 6-membered morpholine) and the specific claim-13 species. I did not fully verify whether that reference also reaches 5-membered-ring N-oxides — that is the one factual gap most worth closing.

2. Two listed citations look spurious. EP 0 035 115 A1 (electronic musical instrument) and EP 0 103 545 A2 (arc-furnace electrode) are chemically unrelated to the NK-1 field; they cannot anticipate anything and appear to be citation-extraction artifacts. I flag them rather than quietly omit them, per the instruction to report each citation as given.

Also not prior art (avoid confusion): the sibling applications in this same family — US 6,593,472 (Ser. No. 09/904,059), US 6,747,026 (Ser. No. 10/337,543), and US 6,897,226 (Ser. No. 10/616,276) — share the priority date (EP 00115287.5, 2000-07-14) and are divisional siblings, not prior art to US 6,806,370. The "Cited By" items (Helsinn netupitant art, etc.) are forward citations and likewise are not prior art to this patent.

Uncertainty statement: Dates and titles above come from the authoritative patent text plus Google Patents/EPO/Justia hits, and are reliable to the extent those sources are; the substantive §102 assessment is my own claim-by-claim reading of the supplied claim text. I could not retrieve the full WO 95/23798 / US 5,691,336 disclosure before my search budget ran out, so the one open question (whether it enumerates 5-membered-ring N-oxides) should be verified directly against that document.

I'll ground this §103 analysis in the actual cited prior art. Let me verify the key references from the "Citations" / "Patent Citations" / "Family Cites Families" sections of the patent page.

Obviousness Analysis — U.S. Patent No. 6,806,370 under 35 U.S.C. § 103

Analyst note on scope and sourcing. Per instruction I am working from the prior-art citations listed on the patent page itself (the "Citations (8)," "Patent Citations (9)," and "Family Cites Families (6)" tables, plus the references discussed in the specification). Where a reference's relevance depends on its full text rather than its title/abstract, I flag that explicitly. I have not auto-corrected any identifier. Priority date used throughout is 2000-07-14 (EP 00115287.5), so pre-2000-07-14 art is the primary target; I note where §102(e)/(a) timing is doing additional work.

1. The claim set to be tested

From the previously generated section (authoritative here), the operative claims are:

• Claim 1 (genus) — amine N-oxides of 4-phenyl-pyridines in which R⁴/R⁴′ together with N form a 5-membered nitrogen-containing ring (0 or 1 additional heteroatom; any S in sulfonyl form), R⁶ = lower alkyl, X = amide/ether, plus the R/R¹/R²/R²′/R³/R³′ variable set.
• Claims 2–4 — species-narrowing of claim 1 (R = methyl; R = chloro; R²/R²′ fused to —CH═CH—CH═CH—).
• Claims 5–8, 9–12 — structurally dependent sub-genera ("compound of claim 1 having the structure…").
• Claim 13 (independent species claim) — the Example 15 compound: (RS)-6-[3-(acetyl-methyl-amino)-1-oxo-pyrrolidin-1-yl]-N-(3,5-bis-trifluoromethyl-benzyl)-N-methyl-4-o-tolyl-nicotinamide (a pyrrolidine-N-oxide).

The critical point for §103 is that the inventive contribution over the specification's own generic formula I is the N-oxide (amine-oxide) prodrug form of an otherwise known NK-1 antagonist chemotype, restricted to the 5-membered cyclic amine version.

2. Prior art on the page, sorted by relevance

3. Legal framework applied

A §103 challenge proceeds under Graham v. John Deere (scope/content, differences, PHOSITA level, secondary considerations), tempered by KSR Int'l v. Teleflex, 550 U.S. 398 (2007) ("a court must ask whether the improvement is more than the predictable use of prior-art elements according to their established functions"), and in the chemical arts, the lead-compound / "reason to modify" rubric of Otsuka v. Sandoz, 678 F.3d 1280 (Fed. Cir. 2012), as applied to prodrugs in In re Apotex (IPR2015-00419, Denial, June 25, 2015) and Merck v. Sandoz, 2015 U.S. Dist. LEXIS 113710 (D.N.J. 2015).

Two structural features determine whether KSR or Otsuka governs: the claimed compounds are prodrugs of known parents, and the differences from the parent art are the N-oxide moiety and a ring-size choice.

4. The combinations

Combination A — HLR parent scaffold + Merck N-oxide-prodrug art (the core §103 case)

Teachings combined:

1. US 6,297,375 / WO 00/50398 / EP 1,155,005 / EP 1,035,115 — disclose the 4-phenyl-pyridine (nicotinamide) NK-1 antagonist genus, including cyclic tertiary amines at R⁴ (pyrrolidine, piperidine, morpholine, piperazine) and amide/ether linkers (X). This supplies every structural element of claim 1 except the N-oxide.
2. WO 95/023798 / US 5,691,336 / GB 2,302,689 — teach that oxidizing the amine nitrogen of a morpholine-class tachykinin (NK-1) antagonist to the N-oxide yields a prodrug with improved aqueous solubility that is reduced back to the parent in vivo. '336 claim 11(1) is literally an N-oxide of a morpholine NK-1 antagonist, and the specification of '370 itself characterizes '336 as "N-oxides" used as prodrugs (an admission in the '370 description).

Motivation to combine (the KSR "articulated reasoning"):

• Same problem, same target. The '370 specification states the reason for the invention: formula II parents "have limited water solubility, not allowing bolus injections," and "it was therefore useful to find derivatives… suitable for parenteral and intramuscular application." The Merck N-oxide references address the identical problem for the identical pharmacological target (tachykinin/NK-1 receptor antagonism).
• Known, class-wide solution. '336 and WO 95/23798 expressly frame N-oxidation as a generic amine-prodrug tactic for this receptor class — a "predictable use of prior-art elements according to their established function" (KSR).
• Reasonable expectation of success. N-oxide prodrugs of tertiary amines were a recognized class by 2000 (e.g., the nalbuphine N-oxide work of U.S. 4,990,617 — external corroboration that N-oxide→parent reduction is a known, plasma-/blood-mediated mechanism). The '370 applicants' own data (t½ 2–18 h in plasma; <30 min in blood) match this known behavior.

Result: Claim 1, and claims 2–4 and 5–12 (which add only routine substituent selections drawn from the parent genera), are prima facie obvious over Combination A.

Combination B — add the 5-membered-ring teaching (for the claim-1 ring-size limitation)

Claim 1 is limited to a 5-membered cyclic amine (pyrrolidine-type), whereas the Merck N-oxide references are framed around morpholine (6-membered). This gap is closed by:

• The parent HLR genera themselves (US 6,297,375 / WO 00/50398), which expressly recite "a five or six membered saturated cyclic tertiary amine" (see the EP 1309559 / YU-8703 counterpart abstract language: "a five or six membered saturated cyclic tertiary amine of the group… which may contain one additional heteroatom"), i.e., pyrrolidine and piperidine are named embodiments of the parent.
• The '370 specification's own equivalence statement: R⁴/R⁴′ "denotes, for example, pyrrolidin-1-yl, piperidin-1-yl, piperazin-1-yl, morpholin-4-yl or 1,1-dioxo-thiomorpholin-4-yl, and the like."

Motivation: 5- and 6-membered cyclic tertiary amine N-oxides are homologous, functionally interchangeable water-solubilizing/reducible prodrug forms; ring-size variation between pyrrolidine and morpholine is a routine optimization. Under KSR, where a technique has been used to improve one device (morpholine N-oxides) and "a person of ordinary skill would recognize that it would improve similar devices in the same way, using the technique is obvious." The Example 9 species (using (R)-3-hydroxypyrrolidine as the parent amine) shows the applicants themselves treated the pyrrolidine variant as an obvious partner for the same chemistry.

Combination C — species claim 13

The Example 15 parent, (RS)-6-[3-(acetyl-methyl-amino)-pyrrolidin-1-yl]-N-(3,5-bis-trifluoromethyl-benzyl)-N-methyl-4-o-tolyl-nicotinamide, is built entirely from substituents enumerated in the HLR parent genera and in formula II of '370 (R⁵ = —N(R³)CO-lower alkyl; the 3,5-bis-CF₃-benzyl amide). Its N-oxide is reached by the routine oxidation of Example 1, step h) / Example 17, step b) (mCPBA or Oxone®) — a classical, high-yielding, predictable amine-to-N-oxide transformation. Claim 13 therefore adds nothing beyond Combination A/B other than the identity of a known parent; under Otsuka/Apotex, once a lead parent is selected, mere N-oxidation thereof is not a patentable difference where the pro-drug rationale is known.

5. Where the §103 case is genuinely contested (and timing caveats)

1. Lead-compound selection. The Apotex and Merck v. Sandoz decisions show courts/PTAB can defeat a prodrug obviousness case at prong (1) when the parent art is a large, data-poor genus and the "right" parent is not singled out (the "wall of prior art" and "601 compounds" problem). Here, however, the challenger is stronger than Apotex was: EP 1,103,545 names the exact parent compound, and US 6,297,375 / WO 00/50398 narrow to a preferred sub-genus — reducing the selection ambiguity that rescued fosaprepitant.

   • Timing caveat: EP 1,103,545's A1 publication appears to post-date '370's 2000-07-14 priority. If it is not available as §102(b)/(a) art, a challenger must rely on its 1999-11-29 priority document (or a PCT/US counterpart) as §102(e) art, or fall back on the genus disclosure in US 6,297,375 (1999-02-24 priority, filed 2000-02-22) which likely discloses or inherently covers the same parent. I have not verified the full text to confirm the exact parent appears in US 6,297,375; this should be checked before relying on it.

2. "Surprising" results / secondary considerations. The '370 specification repeatedly calls the finding "surprising" and reports pKi 8.3–8.7 and plasma/blood t½ data. Patentee would argue (i) unexpected retention of NK-1 affinity by the N-oxide, and (ii) unexpected hydrolytic/reductive stability profile. Rebuttal: N-oxide prodrugs of amines are the expected solution to the solubility problem, and the '370 own data (short blood t½; reduction mechanism "probably catalysed by hemoglobin") confirm the known mechanism rather than an unexpected one. Whether the data rise to "unexpected results" is a factual question; on the face of the specification, they read as ordinary confirmation of a known prodrug strategy.

3. The 5-membered vs. 6-membered limitation is the patentee's best structural distinction, but KSR + the parent genera's express "[five] or six membered saturated cyclic tertiary amine" language makes ring-size substitution a design choice, not an inventive step — provided the parent reference's "five membered" language is citable (it is, via US 6,297,375/WO 00/50398). This should be verified against the full text.

4. Note on the other page-cited references. EP 0035115 A1 (electronic musical instrument), EP 0103545 A2 (arc-furnace electrode), WO 98/04528 A2 (Bayer anti-hypercholesterolemics) and DE 19627431 A1 (Bayer) are not part of any viable §103 combination for this patent; they were presumably cited for formality/unrelated reasons and should not be used to support obviousness.

6. Bottom line

• Strongest combination: [US 6,297,375 / WO 00/50398 / EP 1,155,005 / EP 1,035,115 (HLR parent 4-phenyl-pyridine NK-1 antagonists) — supplying all non-N-oxide structural elements including the recited 5-membered (pyrrolidine) cyclic amine, and the amide/ether X linker — in view of [WO 95/023798 / US 5,691,336 / GB 2,302,689 (Merck)], which teach N-oxides of tachykinin/morpholine antagonists as solubility-improving, in-vivo-reducible prodrugs, optionally corroborated by US 4,990,617 (N-oxide prodrug of a tertiary-amine drug) for the general N-oxide-prodrug principle.
• Motivation: the concrete problem identified in the '370 specification itself — poor aqueous solubility preventing parenteral/bolus use of the NK-1 parent — was already solved for the same receptor class by the very N-oxide chemistry the applicants cite as known. KSR makes this a predictable application of a known technique to a known chemotype.
• Predicted outcome: claims 1–12 would be prima facie obvious; claim 13 would also be obvious once its parent is treated as a selected lead and subjected to routine N-oxidation (Example 1, step h / Example 17, step b conditions). The main non-obviousness rebuttals available to the patentee are (a) a lead-compound-selection/"wall of prior art" argument (weakened by the compound-specific parent art) and (b) unexpected-results evidence (not clearly established on the face of the specification).

Explicit uncertainty statement: This analysis relies on reference titles, abstracts, and claim excerpts retrieved for the page's cited documents; I have not read the complete specifications of WO 95/023798, US 5,691,336, US 6,297,375, WO 00/50398, or EP 1,103,545. Before filing any §103 contention, confirm (i) whether the exact formula-II parent appears in US 6,297,375/WO 00/50398, (ii) the citable date and §102 basis for EP 1,103,545, and (iii) whether the Merck N-oxide references expressly extend beyond morpholine to 5-membered cyclic amines. These three facts control the strength of the combination.