US 3299053

I'll search for this patent number to verify against the authoritative text provided.

Let me verify the litigation history and check for any 2026 CAFC activity.

Search Results Summary — US 3,299,053

Bottom line up front: I located the patent and its well-known litigation history, but I found no CAFC 2026 docket activity involving this number. The patent expired on January 17, 1984, so any 2026 appellate docket would be extraordinary. I state that plainly rather than implying otherwise.

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Bibliographic Data (verified against the authoritative full text)

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Abstract

The patent has no separately labeled "abstract." The specification opens (and this functions as the summary):

"This invention relates to novel 1- and/or 4-substituted amino alkyl 5-aromatic-3H-1,4-benzodiazepines, novel derivatives thereof, novel processes of making the same and novel intermediates useful in the said processes."

The compounds are selected from a genus of 1- and/or 4-(aminoalkyl)-substituted 5-aromatic-3H-1,4-benzodiazepines and their 2-ones, plus pharmaceutically acceptable acid addition salts. They are described as useful anticonvulsants, analgesics, sedatives, muscle relaxants, hypotensive and antidepressants, administrable parenterally or enterally in conventional dosage forms. The patent contains 52 worked examples plus preparation of starting materials (e.g., 2-aminobenzophenones via Bischler-type routes).

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Plain-Language Overview of the Claims

Important caveat on confidence: The claim section as retrieved from Google Patents is heavily OCR-corrupted (formula fragments interleave with text, and claim numbering markers are partly lost). I can confidently describe the shape and categories of the claims and the Markush variables, but I cannot with high confidence reproduce the exact wording or exact dependency of every one of the 26 claims. Anyone needing claim-chart precision should pull the official USPTO/Espacenet PDF image rather than rely on the OCR.

Category A — Compound claims (the bulk of the 26 claims). These are Markush claims directed to a benzodiazepine core having:

• D (the 5-position substituent) — phenyl or pyridyl (with the pyridyl preferably attached at the α-position); the pyridyl species are separately emphasized as a preferred group.
• B — either carbonyl (giving 3H-1,4-benzodiazepin-2(1H)-ones) or methylene (giving 2,3-dihydro-1H-1,4-benzodiazepines).
• n — a whole integer from 2 to 7.
• R₁ and R₂ — individually hydrogen or lower alkyl; or taken together with the nitrogen, a mono-heterocyclic ring (at most one further heteroatom, N or O), specifically recited as N-lower alkylpiperazinyl, N-hydroxy-lower alkylpiperazinyl, N-lower alkoxy-lower alkylpiperazinyl, N-lower alkenyloxy-lower alkylpiperazinyl, pyrrolidinyl, piperazinyl, morpholinyl, and piperidinyl. At least one of R₁ and R₂ must be other than hydrogen in the principal genus — i.e., the claims exclude the simple unsubstituted-aminoalkyl case.
• R₃ — hydrogen, lower alkyl, hydroxy, or lower alkanoyloxy.
• R₄ — hydrogen, halogen, trifluoromethyl, lower alkylmercapto, nitro, cyano, or lower alkyl (some claims omit nitro).
• R₅ — hydrogen, halogen, trifluoromethyl, lower alkyl, or nitro.
• The 1- and/or 4-position substituent is the aminoalkyl side chain –CₙH₂ₙ–N(R₁)(R₂), with the requirement that at least one of the 1- and 4-positions bears this group.

Dependent claims narrow the genus — e.g., to embodiments where R₁ and R₂ are both lower alkyl (a preferred embodiment expressly stated in the specification), to specific 5-aryl/5-pyridyl selections, to the 2-fluoro-phenyl series, and to the hydroxy/lower-alkanoyloxy (e.g., acetoxy) variants at R₃. Pharmaceutically acceptable acid addition salts (HCl, HBr, maleate, etc.) are claimed alongside the free bases, and the maleate/dimaleate salts are exemplified throughout.

Category B — Process claims. The patent also claims methods of making the compounds, generally:

1. One-step N-alkylation: reacting a 1-sodio derivative of a 5-aromatic-3H-1,4-benzodiazepine (1-position unsubstituted) with an amino-lower-alkyl halide X–CₙH₂ₙ–N(R₁)(R₂), in an inert organic solvent (methanol, ethanol, DMF, benzene, toluene, N-methylpyrrolidone), at room temperature or elevated temperature/pressure, with sodium methoxide or sodium hydride used to form the sodio derivative.
2. Two-step (haloalkyl-then-amine) route: reacting the sodio derivative with a dihaloalkane X–CₙH₂ₙ–X′ (preferably 1-bromo-3-chloropropane, 2-bromoethyl chloride, or 1-bromo-4-chlorobutane) to give the novel haloalkyl intermediate (Formula IV/V — separately claimed as intermediates and stated to be useful as anticonvulsants), then displacing the remaining halogen with a primary or secondary amine H–N(R₁)(R₂), preferably in the presence of an alkali halide such as sodium iodide, in acetone, methyl ethyl ketone, methanol, ethanol, DMF, benzene, nitromethane, or N-methylpyrrolidone.
3. Reduction step: reducing the 4-oxide (or the 2-one) with hydrogen over a hydrogenation catalyst (e.g., platinum oxide, Raney nickel) to give the corresponding 4,5-dihydro / 2,3-dihydro compounds, which can in turn be N-alkylated with lower alkyl, lower alkenyl, or lower alkynyl halides, or with the amino-lower-alkyl halide.
4. Ancillary transformations described (and likely reflected in dependent process claims): acylation of the 3-hydroxy with a lower alkanoic anhydride (e.g., acetic anhydride) to give the 3-lower-alkanoyloxy compound; hydrolysis of that ester with alkali or alkaline earth metal hydroxide or mineral acid back to the 3-hydroxy; reduction of an aromatic nitro (R₄) with Raney nickel to the amine; and diazotization/chlorination of that amine (nitrous acid/HCl then CuCl) to install halogen.

Salts/utility: Pharmaceutically acceptable acid addition salts formed with 1 or more moles of acid (depending on basic nitrogens) are claimed; the specification recites HCl, HBr, H₂SO₄, H₃PO₄, HNO₃, citric, tartaric, salicylic, toluenesulfonic, ascorbic, maleic, succinic, formic, and acetic acids.

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Commercial Significance — the compound behind the patent

The commercially important species within this genus is flurazepam hydrochloride (the active ingredient in Roche's DALMANE), which is 7-chloro-1-(2-diethylaminoethyl)-5-(2-fluorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one and its salts. This compound corresponds to the chemistry of Examples 7, 9, and 28 of this patent (the 2-fluorophenyl / N,N-diethylaminoethyl series). Note that the patent's own nomenclature switches between "4,5-dihydro" and "1,3-dihydro" for these reduced species, which is a source of naming ambiguity in the specification.

The patent is also cited in connection with fludiazepam (per the Spanish-language Wikipedia entry returned in search), though fludiazepam's 1-methyl-5-(2-fluorophenyl) structure is not among the worked examples I can see.

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Litigation — What I Actually Found

The only significant patent litigation I can confirm is over 40 years old:

• Roche Products, Inc. v. Bolar Pharmaceutical Co., 733 F.2d 858 (Fed. Cir. 1984) (also reported at 221 USPQ 937). The Federal Circuit held that Bolar's importation and FDA-required bioequivalence testing of flurazepam HCl during the patent term infringed the '053 patent, rejecting the experimental-use defense. The court expressly declined to create a public-policy exception for FDA testing, saying that was Congress's role.
• The district court (E.D.N.Y., Judge Debevoise) had held no infringement; the Federal Circuit reversed.
• Congress responded with the Drug Price Competition and Patent Term Restoration Act of 1984 (Hatch-Waxman), whose 35 U.S.C. § 271(e)(1) safe harbor effectively overturned Roche v. Bolar.
• Darts-ip lists this patent family (family=23348328) as having "first worldwide family litigation filed," pointing to the same Roche/Bolar dispute.

On the specific request about a CAFC 2026 docket: My searches returned no CAFC 2026 docket, appeal, or opinion involving US 3,299,053. Given the patent expired January 17, 1984 — 42 years ago — and no term extension is recorded in the file, current CAFC activity is not plausible. If you have a specific 2026 docket number, please provide it and I will search it directly; I do not want to speculate on a docket I cannot verify.

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Explicit Uncertainty Flags

1. Claim text: OCR corruption prevents me from reproducing the 26 claims verbatim with confidence. The genus structure and Markush variables above are reliable; individual claim numbering and dependency are not.
2. "Abstract": This 1967 patent has no formal abstract field; what I quoted is the opening paragraph of the specification.
3. CAFC 2026: Not found. Stated as not found rather than inferred.
4. Assignee chain: Google Patents flags the listed assignees as potentially inaccurate; the 1983 reassignment to Roche Products Inc. (Panama) is a recorded assignment of interest from Roche Products Inc. (a DE corp.), per the file record.

Sources: https://patents.google.com/patent/US3299053A/en ; https://worldwide.espacenet.com/publicationDetails/originalDocument?CC=US&NR=[3299053A](/patent/3299053A) ; https://patents.darts-ip.com/?family=23348328 ; https://www.courtlistener.com/opinion/[435131](/patent/435131)/roche-products-inc-v-bolar-pharmaceutical-co-inc/

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

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

I found a key case. Let me verify details and search for any additional litigation.

Litigation Involving U.S. Patent No. 3,299,053

I searched litigation-oriented sources (Google Patents/Darts-ip family page, CourtListener, Justia, law.resource.org, nathenson.org case archive) for the exact number 3,299,053. One U.S. case is directly on point. I did not find any other U.S. litigation naming this patent.

Case 1 — Roche Products, Inc. v. Bolar Pharmaceutical Co., Inc. (the "Bolar" case)

Significance: This decision is the origin of the so-called "Bolar exemption." Congress responded by enacting 35 U.S.C. § 271(e)(1) (the Hatch-Waxman Act, 1984), which overturned the Federal Circuit's holding by exempting acts of making, using, or selling a patented invention solely for uses reasonably related to FDA-approval submissions.

Foreign / related proceedings (not U.S. Patent 3,299,053)

For completeness, my searches surfaced benzodiazepine litigation involving Roche's foreign counterparts and other patents — these do not name U.S. 3,299,053 and should not be conflated with it:

• Canada: Hoffmann-La Roche Ltd. v. Bell-Craig Pharmaceuticals (compulsory-license proceedings re: chlordiazepoxide/Librium; Canadian Patent Act s. 41).
• United Kingdom: Hoffmann-La Roche & Co. A.G. v. D.D.S.A. Pharmaceuticals (passing-off/capsule get-up for chlordiazepoxide "CDP"/Librium, a different patent).

Caveats

• Google Patents' page for US3299053A carries a Darts-ip "First worldwide family litigation filed" link (family 23348328), confirming the family has a recorded litigation history, but the underlying Darts-ip records are behind a paywall and I could not enumerate them beyond the Bolar case.
• I did not identify any other U.S. district court or CAFC/PTAB proceedings naming 3,299,053 specifically. The number 3,299,053 predates the AIA, so no IPR/PGR would apply.
• I searched by the exact digits; results referencing other "905"/"053" patents (e.g., design patent D352,905, or patents in the Sony/Fujifilm LTO dispute) were excluded as different patents.

If you need a docket-level confirmation (e.g., PACER/RECAP for D.N.J. and E.D.N.Y. filings, or a Darts-ip report), those would require a paid database or PACER access beyond what was available here.

I'll verify the structured data against what's publicly discoverable before writing up.

Let me confirm the only real adversarial history on this patent and rule out reexaminations.

Proceedings overview

Total AIA trial proceedings on file for US 3,299,053: zero (0). The USPTO ODP structured block reports no AIA trial proceedings, and my searches surfaced no IPR, PGR, or CBM petition, no PTAB Final Written Decision, and no ex parte reexamination certificate tied to this patent — so the breakdown by status is simply: active 0 / claims invalidated 0 / claims sustained 0 / settled 0 / institution denied 0. The defensive posture this gives a defendant is not "hardened patent" but "no case at all": the '053 patent issued 1967-01-17 and its 17-year term expired 1984-01-17 (Google Patents legal status: "Expired - Lifetime"; anticipated expiration 1984-01-17), so there are no in-force claims left for anyone — PTAB or plaintiff — to assert. The absence of PTAB activity is not a signal about patent strength; it is a function of the AIA trial regime (IPR available from 2012-09-16, CBM sunset 2020-09-16, PGR only for effective filing dates on/after 2013-03-16) postdating this patent's expiration by nearly three decades.

I did not invent proceeding numbers to fill this section. There are none.

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Non-PTAB enforcement history (the only adversarial record on this patent)

E.D.N.Y. No. CV 83-4312 / Fed. Cir. Appeal No. 84-560 — Roche Products, Inc. v. Bolar Pharmaceutical Co., Inc.

Not an AIA trial proceeding. Included because it is the only litigation on the '053 patent and because Google Patents flags the family as "Family has litigation / First worldwide family litigation filed."

• Type: District court patent infringement action (35 U.S.C. §§ 271, 283), appealed to the U.S. Court of Appeals for the Federal Circuit. Not an IPR/PGR/CBM.
• Filed: Complaint originally filed in the U.S. District Court for the District of New Jersey (secondary sources give 1983-07-28; the E.D.N.Y. opinion does not state the filing date — treat that date as reported, not confirmed). That court (Judge H. Lee Sarokin) issued a temporary restraining order on 1983-09-02; venue was transferred to the E.D.N.Y. under 28 U.S.C. § 1406(a).
• Status: Fully terminated by 1984. Final CAFC decision 1984-04-23. The '053 patent expired 1984-01-17, mid-appeal; the CAFC held the case was not moot because a remedy for past infringement could still be fashioned.
• Judge panel: District: Judge Leonard D. Wexler (E.D.N.Y.), memorandum and order dated 1983-10-11, judgment entered 1983-10-14, reported at 572 F. Supp. 255 (E.D.N.Y. 1983). Federal Circuit: Chief Judge Howard T. Markey, Senior Circuit Judge Philip Nichols, Jr., Circuit Judge Shiro Kashiwa, reported at 733 F.2d 858 (Fed. Cir. 1984).
• Petition grounds: N/A — this was an infringement action, not a validity challenge. Critically, validity was not contested: the district court stated, "There is no argument that the patent is for a pioneer invention and is valid and in force." So there is no judicial validity holding on any claim of the '053 patent, and no claim was ever canceled or sustained by any tribunal.
• Institution decision: N/A.
• Final written decision: N/A. The merits disposition was on infringement only:
  • District court: held that Bolar's FDA-mandated bioequivalence testing on imported flurazepam HCl during the last six months of the patent term was a de minimis, non-infringing experimental use; denied a permanent injunction and dissolved the TRO.
  • Federal Circuit: reversed and remanded. Quoting the opinion: "Bolar's intended 'experimental' use is solely for business reasons and not for amusement, to satisfy idle curiosity, or for strictly philosophical inquiry. Bolar's intended use of flurazepam hcl to derive FDA required test data is thus an infringement of the '053 patent." Disposition: "The decision of the district court holding the '053 patent not infringed is reversed. The case is remanded with instructions to fashion an appropriate remedy. Each party to bear its own costs." Roche had asked for, inter alia, confiscation and destruction of Bolar's test data; the CAFC left the form of remedy to the district court, and I could not confirm what remedy (if any) was ultimately ordered on remand.
  • Claim-level granularity: none. The CAFC did note that "one of the chemical compounds claimed in the '053 patent is flurazepam hydrochloride," but it did not identify claim numbers or parse individual claims — do not attribute claim-level findings to this case.
• Settlement / termination: No settlement. The case was decided on the merits and remanded.
• Appeal: The district court judgment was appealed to the Federal Circuit (Appeal No. 84-560), which reversed. Opinion: https://law.justia.com/cases/federal/appellate-courts/F2/733/858/[459501](/patent/459501)/ and https://law.resource.org/pub/us/case/reporter/F2/733/733.F2d.858.84-560.html. I cannot confirm with high confidence whether a certiorari petition was filed and denied, so I make no representation on Supreme Court review.
• Defensive value today: Effectively zero risk from this precedent. Roche's win was legislatively reversed: § 271(e)(1) (Hatch-Waxman, Pub. L. 98-417, Title II, 1984) was enacted to "have the net effect of reversing the holding of the court in Roche Products, Inc. v. Bolar Pharmaceutical Co." (H.R. Rep. No. 98-857, pt. 2, at 27). Any theory that pre-expiration FDA testing on a compound infringes is now statutorily barred — the Roche holding is a dead letter and a defendant in a hypothetical assertion could cite the very statute Congress passed to kill it.

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Strategic summary

Claim status: no claims are canceled, sustained, or even adjudicated — they are simply expired. There is no IPR certificate canceling any of the 26 claims, and there is no FWD holding any claim patentable. The only thing that has ever been decided about the '053 patent is that unlicensed FDA-motivated use of flurazepam HCl during the term infringed it (Roche, 733 F.2d at 863) and that the patent was presumed valid and unasserted on validity (572 F. Supp. at 256). The entire claim set — independent claims, flurazepam-specific claims, and dependents — went out of force on 1984-01-17, which is why Google Patents reports "Expired - Lifetime" and an anticipated expiration of 1984-01-17. If you need the literal claim text, the authoritative source is the patent document itself: https://patents.google.com/patent/[US3299053A](/patent/US3299053A)/en.

Estoppel landscape: there is none, because there was no IPR. § 315(e)(2) estoppel attaches only to petitioners and their privies in an instituted IPR; with no petition ever filed, no party is estopped, and there is no PTAB record (no institution decision, no FWD, no appeal) to constrain anyone. Symmetrically, there is also no IPR-based defense to inherit. That sounds bad for a defendant, but it is irrelevant here: because the patent expired in 1984, § 271(a) liability requires the accused acts to occur "during the term of the patent," and § 286's six-year damages lookback cannot reach past 1984. A demand letter citing this patent is either a mistake or a bad-faith shakedown; the correct response is a one-line expiration/standing letter, not an IPR.

Pattern signals. No repeat-petitioner pattern (zero petitioners), no patent-owner PTAB appeal activity, no defensive aggregator (no Unified Patents, RPX, or similar involvement — nothing surfaced in search). The Darts-ip "first worldwide family litigation" flag on the Google Patents family page corresponds to the Bolar dispute and its foreign counterparts, not to any post-grant proceeding. Note also the family's GB priority documents (GB1052144, GB1051795) and the large 1965 foreign filing wave (DE1545933–1545936, NL6501578/6501579/6501631, BE659442–659445, etc.) — this was a commercially significant Roche compound family in the 1960s–70s, which is exactly why it drew litigation then and nothing since.

Recommended next steps

• If you are a defendant and the patent has claims invalidated: it does not. Do not represent to a court or client that any claim was canceled — no proceeding exists. Say instead that the patent expired 1984-01-17 and no live claims remain.
• If you are considering a PTAB filing: don't. There is no infringement exposure to reduce, the patent is decades expired, and the PTAB is not the right forum — even where IPR of an expired patent is technically possible, the current institution environment (Director-controlled institution since the October 2025 Squires memorandum, plus an explicit "settled expectations"/patent-age factor) makes institution on a 1967 patent a practical non-starter. Proposed rules published 2025-10-15 would further narrow petitioner access. Verify current practice before relying on any of this.
• No active proceedings, so no trial-stage milestones to track: no institution decision deadline, no oral hearing date, no statutory one-year FWD due date (35 U.S.C. § 316(a)(11)) is applicable.
• The absence of PTAB activity is the correct and expected answer here. Well-asserted patents attract IPRs — this one was asserted only in an era before IPRs existed, and only on a compound whose statutory safe harbor now lives at 35 U.S.C. § 271(e)(1).
• If you want a belt-and-suspenders record, pull the PTAB E2E docket search yourself for the patent number (https://ptacts.uspto.gov/ptacts/) and the USPTO patent-status page (https://patentcenter.uspto.gov/), and confirm the assignment/reassignment history (Google Patents shows a 1983-01-21 assignment to Roche Products Inc. and a 1984-01-17 anticipated expiration). None of these should change the answer, but the citation to the primary docket is worth having in the file.

Confidence notes: (1) The zero-proceeding finding is sourced from the USPTO ODP structured block and corroborated by searches; I found no contrary evidence, but I cannot prove a negative for dockets not indexed online. (2) The 1983-07-28 complaint filing date comes from secondary sources, not the opinion. (3) I did not confirm any certiorari disposition in Roche v. Bolar, nor the remedy ordered on remand — both are marked unknown rather than guessed.

I'll start by attempting to retrieve the assignment records from public sources.

Let me probe further for the assignment-chain specifics and any litigation/ownership records.

Ownership Analysis — US Patent 3,299,053

Scope note / data limitation (read first): I could not retrieve the actual Assignment Center records for this patent. The USPTO's Assignments on the Web (AOTW) database only contains records filed on or after August 1980 (per Finnegan's description of the system, cited below), and assignment documents are not electronically available — they must be ordered from the USPTO for a fee. This patent was filed in 1964, issued in 1967, and expired in 1984. I therefore have no reel/frame numbers to cite for this chain, and I will not invent them. What follows is built from the patent front page itself, the Google Patents legal-events record, and the Federal Circuit's reported ownership findings in Roche Products, Inc. v. Bolar Pharmaceutical Co., 733 F.2d 858 (Fed. Cir. 1984).

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Inventors

All four were Roche research chemists; Sternbach was the Roche chemist credited with the benzodiazepine series (the chlordiazepoxide/diazepam work) and the group worked corporately in Nutley. The patent is a continuation-in-part of Archer/Fryer/Reeder/Sternbach applications Ser. Nos. 176,901 (filed March 2, 1962) and 259,753 (filed February 19, 1963), both abandoned — i.e., a purely in-house, corporate-inventor filing, not an acquired-in portfolio.

Unusual patterns: None of the tell-tale "inventors depart within 12 months" pattern. Reeder and Sternbach are well documented as long-tenured Roche employees; there is no evidence of inventor-side divestment, and none of the four appear as assignors to any third party in any record I could locate. Note the assignment to Roche was executed before issuance as a matter of routine corporate practice (the patent face reads "assignors to Hoffmann-La Roche Inc."), not by a separate recorded instrument I can verify.

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Original assignee

Hoffmann-La Roche Inc., Nutley, N.J., a corporation of New Jersey.

• Product embodying the claims: Yes. The claims cover flurazepam hydrochloride (the compound of the patent), the active ingredient in Dalmane, Roche's brand-name hypnotic. In the Bolar litigation Roche's counsel and the court recorded plaintiff's Dalmane sales as "in excess of $40,000,000 annually" (572 F. Supp. 255, 256 (E.D.N.Y. 1983)).
• Primary line of business: Pharmaceutical R&D and manufacturing — the U.S. operating subsidiary of F. Hoffmann-La Roche & Co. AG (Basel).
• Current status: Operating/restructured. Roche's U.S. operations persist today (Genentech is a Roche Group member); the 1983 corporate steps described below are intra-group reorganizations, not insolvency. No bankruptcy, no dissolution of the Roche group.

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Assignment timeline

The USPTO Assignment Center returns no electronically verifiable chain-of-title records for this patent. The Google Patents legal-events feed for US 3,299,053 shows exactly one post-issuance reassignment entry and one expiration entry, and supplies no reel/frame:

• 1983-01-21 — (execution date not stated in the public feed) / recorded on the legal-events date shown as 1983-01-21 — Reel/Frame: not available in the sources retrieved (USPTO AOTW does not expose records predating Aug. 1980 in electronic form; no reel/frame is printed in the retrieved record)

  • Conveyance: Assignment / reassignment (Google Patents labels it "reassignment")
  • Assignor: Roche Products Inc., a Delaware corporation
  • Assignee: Roche Products Inc., a Panama corporation
  • Correspondent: Not available — no correspondent name, firm, or address is exposed in the retrieved record. (This is precisely the field where an NPE chain would be most revealing, and it is absent here.)
  • Context: Internal corporate reorganization — same root name on both sides of the instrument; a Delaware parent/affiliate re-domiciling the holding entity to Panama. Not a transfer to a third party, not a securitization, not a fire-sale.

• 1984-01-17 — no assignment; anticipated expiration of the 17-year term (Google Patents legal event). Confirmed by the courts: "Plaintiff's seventeen year patent expires on January 17, 1984."

Gap in the chain — explicit caveat: The patent face names Hoffmann-La Roche Inc. (New Jersey) as assignee, but the 1983 plaintiff of record was Roche Products, Inc. (see below). An intermediate transfer from Hoffmann-La Roche Inc. to Roche Products, Inc. must therefore exist for Roche Products to have held standing to sue, but I could not locate a recorded instrument for it — and any such instrument executed before August 1980 would fall outside the electronic AOTW database, which is consistent with the record being invisible. I flag this as a documentation gap, not as an assignment I can cite. Google Patents lists three entities under "Current Assignee" (F. Hoffmann La Roche AG; Hoffmann La Roche Inc; Roche Products Inc.), which is consistent with an unbroken intra-group chain.

If you need the reel/frame for the 1983 instrument, it must be ordered from the USPTO Assignment Recordation Branch (the document is not electronically retrievable).

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Timeline diagram

timeline
    title Ownership of US 3299053
    1964 : Filed by Archer Fryer Reeder Sternbach
         : Assigned to Hoffmann-La Roche Inc
    1967 : Patent issued as US 3299053
    1983 : Reassignment to Roche Products Panama
         : Roche sues Bolar over Dalmane
    1984 : Patent expires January 17

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NPE / troll-pattern signals

1. Shell-entity transfer — not present. The only third-party-looking entity in the chain, "Roche Products Inc. (Panama)," shares its exact corporate name with the assignor ("Roche Products Inc., a Delaware corporation"). That is the signature of a re-domiciliation, not a transfer to a licensing-only shell. There is no recorded assignment to any entity with an "IP / Patents / Licensing / Holdings / Ventures" suffix anywhere in the retrieved record, and no registered-agent address appears.

2. Known asserter in the chain — not present. No assignee in the chain matches any published NPE/asserter list (Acacia, Marathon, IV, IPNav, Wi-LAN, Mosaid/Conversant, Vringo, Pendrell, Round Rock, etc.). Assignees of record are Roche entities only.

3. Repeat correspondent across the chain — unclear / not assessable. No correspondent is exposed in the only retrieved record. Note for contrast: the litigation counsel of record for Roche was John C. Vassil, P.C., of Morgan, Finnegan, Pine, Foley & Lee (572 F. Supp. 255, 256), but litigation counsel is not assignment-recordation correspondent and is not a signal here.

4. Cascading transfers — not present. Only one recorded transfer exists in the retrieved record, executed roughly 16 years after issuance. No chained LLCs, no cluster of transfers within 24 months.

5. Pre-litigation transfer — not present (with one caveat worth stating precisely). The recorded reassignment is dated/recorded 1983-01-21; Roche filed its New Jersey complaint against Bolar on July 28, 1983 — approximately six months and one week later. That proximity is superficial only: both sides of the instrument are Roche group entities, so the transaction transferred nothing to an asserter and cannot have been arranged to establish standing for a third party. It was an internal re-domiciliation, and the plaintiff's standing rested on the pre-existing intra-group chain.

6. Bankruptcy fire-sale — not present. No Chapter 7/11 proceeding involving an assignor or assignee appears in the record; Roche has not been in bankruptcy. The patent simply expired at end of term (1984-01-17).

7. Privateering — not present. Roche litigated US 3,299,053 itself, as patentee/plaintiff of record, against an actual generic competitor (Bolar) over an actual product (Dalmane). That is conventional operating-company enforcement, the opposite of privateering. There is no evidence of a Roche→NPE transfer asserting on Roche's behalf; Darts-ip's family record (family 23348328) flags the family as litigated, and the reported litigation is the Roche v. Bolar line, not a proxy suit.

8. Defensive aggregator — not present. The chain never touches RPX, AST, LOT, Unified Patents, or OIN. The patent expired in 1984, well before those entities existed.

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Verdict

Operating-company assertion.

Roche's own affiliate held and asserted the patent: Roche Products, Inc. sued Bolar Pharmaceutical on July 28, 1983 in D.N.J. (later transferred to E.D.N.Y.), seeking to enjoin a generic competitor's FDA-required testing of flurazepam HCl — the compound of the claims — and plaintiff's Dalmane sales were recorded as exceeding $40 million annually (572 F. Supp. 255, 256; rev'd, 733 F.2d 858 (Fed. Cir. 1984)). The sole post-issuance recorded event, the 1983-01-21 reassignment of Roche Products Inc. from its Delaware form to its Panama form, is an intra-group re-domiciliation between identically named Roche affiliates — not a transfer to an asserter — after which the patent simply expired on 1984-01-17. No NPE signal is present, and the absence of an electronically retrievable chain (AOTW coverage begins Aug. 1980) is a documentation artifact of the patent's age, not evidence of concealment.

Verify at: https://assignmentcenter.uspto.gov/ (search patent 3299053); the indexed mirror is https://assignment.uspto.gov/patent/index.html. Expect only the post-August-1980 slice of this chain to return.

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Sources

• US 3,299,053, Google Patents — https://patents.google.com/patent/US3299053/en (front page; legal events: 1983-01-21 reassignment to Roche Products Inc. Panama, 1984-01-17 anticipated expiration).
• Roche Products, Inc. v. Bolar Pharmaceuticals Co., 572 F. Supp. 255 (E.D.N.Y. 1983) — https://app.midpage.ai/document/roche-products-inc-v-bolar-pharmaceuticals-co-[2310125](/patent/2310125)
• Roche Products, Inc. v. Bolar Pharmaceutical Co., 733 F.2d 858 (Fed. Cir. 1984) — https://law.justia.com/cases/federal/appellate-courts/F2/733/858/[459501](/patent/459501)/
• Darts-ip family record for US3299053 — https://patents.darts-ip.com/?family=23348328
• Finnegan, "Who Owns What: Finding Patent Assignment Information" (AOTW coverage since Aug. 1980; documents not electronically available) — http://www.finnegan.com/print/content/24547/Who-Owns-What-Finding-Patent-Assignment-Information.pdf

I'll search for the specific patent and its cited prior art references.

Let me search more specifically for the citation/reference sections of this patent.

Let me try to locate the patent's front page (references cited) and the USPTO record directly.

Step 1 — USPTO record for the exact number 3299053

I searched for the specific identifier 3299053 (not 3,299,053-similar numbers). I could reach the Google Patents mirror of the USPTO full text (which reproduces the printed patent, including the "United States Patent" header, the "26 Claims. (Cl. 260—239.3)" line, and the "No Drawing. Filed Feb. 11, 1964, Ser. No. 343,941" line) and the Espacenet original-document record. The USPTO PatentCenter/Assignment links appear on the Google Patents page.

Verified bibliographic record for US 3,299,053:

Governing law for the § 102 analysis: the application was filed February 11, 1964, so pre-AIA 35 U.S.C. § 102 applies in its entirety (AIA first-inventor-to-file provisions govern only applications filed on or after March 16, 2013). The critical § 102(b) statutory-bar cut-off date is therefore February 11, 1963 (one year before filing), and the § 102(a) "before the applicant's invention" date runs from the 1962/1963 CIP parents.

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Step 2 — Honest limitation: I could not retrieve a populated "References Cited" list from the patent's face

This is the key finding, and I will not paper over it:

• Google Patents' page for US3299053A did not surface a populated "Patent Citations" / "(56) References Cited" table in any of my queries. Every search hit that displayed the string "US3299053A" in a citation table was a page for a different patent that cites '053 (i.e., a forward citation), not '053's own cited art.
• The one hit that appeared to show a citations table (Google Patents page for US 2,532,292, "Diarylmethyl ethers of amino alkanols," listing US2397799A / US2421714A / US3299053A under "Citations (3)") is internally inconsistent — a patent granted in 1950 cannot cite a patent issued in 1967. I treat that record as a Google Patents data artifact and do not rely on it.
• I did not obtain a direct API/PatFT query of the USPTO "References Cited" field for 3,299,053. That is a gap in my evidence, stated plainly rather than filled with invention.

Consequence: I cannot give you a verbatim, face-of-the-patent examiner citation list. What follows is (A) the prior art I can ground in the authoritative record itself, and (B) the surrounding benzodiazepine art, clearly flagged as to whether I can confirm it appears on the '053 face. Anyone needing the certified citation list should pull the front page of the printed patent image (USPTO PatentCenter, or Espacenet original document).

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Step 3 — Prior art grounded in the '053 record itself (high confidence)

The '053 specification repeatedly and expressly designates compounds as "not a part of this invention" while describing their preparation "in order that this disclosure may be complete." These self-identified admissions are the closest thing to an authoritative prior-art list in the document:

§ 102 takeaway: none of these anticipates, because the point of novelty of '053 is precisely the 1- and/or 4-(ω-aminoalkyl) substituent (with at least one of R₁/R₂ other than hydrogen), which none of the acknowledged cores or intermediates contains. If any of these were cited by the examiner, they were cited as background/§ 103 art, not as § 102 anticipation.

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Step 4 — The foreign family members (dates matter, and they cut against anticipation)

From the Google Patents family record, the following were filed after the February 11, 1964 US filing and are the same invention by the same inventors:

• GB 1,052,144 and GB 1,052,179 (priority Feb. 11, 1964)
• DE 1,545,933 A1, DE 1,545,934, DE 1,545,935, DE 1,545,936 B2 (priority Jan. 28–Feb. 1, 1965)
• CH 460,793 / CH 460,030 / CH 457,466 / CH 453,369 / CH 467,787 / CH 458,372; NL 6501578 / NL 6501579 / NL 141781; FR 1,455,059, FR 1,443,116, and the M-certificates FR 4123M / FR 4138M / FR 4609M / FR 4772M; IL 22,869 / 22,902 / 22,903 / 22,935; NO 117,367 / 118,273 / 119,798 / 118,747; DK 118,249 / 107,032 / 105,984; SE 307,952 / 307,953 / 309,597 / 321,477; ES 309,167–309,170; BR 656,7051/7053/7054/7055

§ 102 analysis: these all post-date the US filing, so none is § 102(a) or § 102(b) art against '053. For completeness on the same-inventor problem generally: a foreign patent granted to the same inventors is not § 102(a) art ("by others"), and a foreign patent does not create § 102(b) statutory bars for the applicant's own disclosure unless it was published more than one year before the US filing.

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Step 5 — Surrounding benzodiazepine art (flagged: I could NOT confirm any of these appear on the '053 face)

The art that a 1964–1966 examiner plausibly considered is the Sternbach/Roche and American Home Products 1,4-benzodiazepine corpus. I list these because you asked for "the most relevant prior art," but I flag each: I have not verified these appear in the '053 References Cited field. Do not treat this list as the certified citation list.

Bottom line on § 102: I found no single reference that discloses a species falling within the '053 genus — i.e., a 5-aryl-3H-1,4-benzodiazepin-2-one or 2,3-dihydro-1H-1,4-benzodiazepine bearing a –CₙH₂ₙ–N(R₁)(R₂) group (at least one of R₁/R₂ ≠ H) at N-1 and/or N-4, with the recited R₃/R₄/R₅ Markush. That is consistent with the claims having issued without an anticipation rejection. The unsubstituted cores that the specification itself concedes are old cannot anticipate any of the 26 claims, because every claim carries the aminoalkyl substituent as an element.

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Step 6 — Forward citations ("Cited By") — found, and genuinely useful

Although this is the inverse of what you asked, it is the one citation direction I could verify, and it demonstrates the patent's blocking position in the 1,4-benzodiazepine field:

• US 3,609,146 — "Substituted benzodiazepinone derivatives" (filed 1968; issued Sept. 28, 1971) — lists US3299053A among its "Patent Citations." Source: https://patents.google.com/patent/[US3609146A](/patent/US3609146A)
• US 4,008,223 / RE31071 — "6-Aza-3H-1,4-benzodiazepines" — lists US3299053A among its citations. Source: https://patents.google.com/patent/US4008223
• The Google Patents record at https://patents.google.com/patent/US3299053A/en carries a Darts-ip "First worldwide family litigation filed" link (family 23348328), pointing to the Roche Products v. Bolar Pharmaceutical flurazepam litigation (573 F. Supp. 255 (E.D.N.Y. 1983), rev'd, 733 F.2d 858 (Fed. Cir. 1984)) — already covered in the prior litigation section of this analysis, so I will not repeat it here.

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Step 7 — Explicit uncertainty flags

1. Certified citation list not obtained. I could not retrieve a populated "(56) References Cited" / "Patent Citations" table for US 3,299,053. The list in Step 5 is constructed from the field literature and the specification's own admissions, not from the patent's face. Treat it as a candidate set, not as the examiner's citation list.
2. Google Patents citation-table artifact. The US 2,532,292 entry showing US3299053A under "Citations (3)" is chronologically impossible (1950 patent citing a 1967 patent) and was excluded.
3. Claim numbering. As flagged in the earlier summary, the OCR of the 26 claims of '053 is corrupted. My § 102 mapping is by claim content (the principal genus claim; the claim requiring R₁ and R₂ each to be lower alkyl; the 2-fluoro-phenyl species claims; the process claims; the Formula IV/V intermediate claims), not by reliably-read claim numbers.
4. Pre-AIA regime. All § 102 conclusions above are under pre-AIA § 102(a)/(b)/(e)/(g). No AIA § 102(a)(1)/(a)(2) analysis applies to a 1964 filing.
5. No 2026 activity. Nothing in these searches shows any USPTO or court proceeding involving 3,299,053 in 2026; the patent expired January 17, 1984, and no term extension appears in the file record.

Sources used: https://patents.google.com/patent/US3299053A/en · https://worldwide.espacenet.com/publicationDetails/originalDocument?CC=US&NR=[3299053A](/patent/3299053A) · https://patents.google.com/patent/US3609146A · https://patents.google.com/patent/US4008223 · https://patents.darts-ip.com/?family=23348328 · https://patents.google.com/patent/US2532292 (excluded as unreliable)

I'll research the prior art relevant to this patent's claims before mapping out §103 combinations.

Let me pull the specific prior-art references and prosecution citations.

Let me verify what the key Sternbach/Reeder prior patents actually disclose about 1-position alkylation.

Obviousness Analysis — U.S. Patent No. 3,299,053 under 35 U.S.C. § 103

0. Scope note and a flagged premise issue

Your instruction was to "use the results from the Prior Art section of this page." I have to flag what that section actually contains, because it constrains what I can honestly do here.

On the Google Patents page for US3299053A, the "Prior Art" block is not a reference list. It contains only:

• Prior art keywords: benzodiazepin, chloro, solution, mixture, dihydro
• Prior art date: 1964-02-11

The page as retrieved contains no "References Cited" / "Patent Citations" / "Non-Patent Citations" table (Google Patents normally renders one, but it is absent from the fetched text at https://patents.google.com/patent/US3299053A/en). Accordingly, I cannot report the examiner-cited art for this patent, and I will not invent it. What follows is an independent §103 analysis built from (a) the patent's own admission of what is old, and (b) prior-art references I could actually locate and verify in search results, with each reference's statutory basis and date stated. Where I could not verify a reference's content, I say so.

Also carrying forward from the earlier sections: the claim text is OCR-corrupted, so I analyze the claims at the level of their Markush categories, not verbatim claim language. The earlier sections established the genus (1- and/or 4-(aminoalkyl)-5-aryl-3H-1,4-benzodiazepines and their 2-ones, B = carbonyl or methylene, n = 2–7) and identified flurazepam as the commercial species.

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1. Legal framework and the critical dates

This is a pre-AIA patent (filed Feb. 11, 1964; issued Jan. 17, 1967). Pre-AIA § 103(a) governs. The Graham v. John Deere factors apply, as refined by KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007).

Critical dates matter more than usual here because this application is a CIP. The specification states (verified in the full text):

"This application is a continuation-in-part of applications Serial Nos. 176,901, filed March 2, 1962 and 259,753, filed February 19, 1963… Both of the aforesaid applications are now abandoned."

That produces two distinct prior-art cutoffs:

Two consequences I want to make explicit:

1. Subject matter first added in the Feb. 11, 1964 CIP (i.e., not supported in the 1962/1963 parents) gets no earlier date — so for those claims, the art date is the invention date, but all patentably distinct later-added species remain exposed to art dated between Mar. 1962 and Feb. 1964.
2. Pre-AIA § 103(c) (added 1984) did not exist in 1964, and by its terms applies only to applications filed on or after Nov. 8, 1984. Several of the closest references are Roche's own (Reeder/Sternbach). Common ownership therefore does not remove them from the § 103 combination. In any event, the two strongest references below are a 1959 patent and a 1962 journal article, neither of which qualifies "only under § 102(e)(f)(g)" — so no common-ownership exception would reach them even under today's statute.

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2. The prior art of record (verified references)

Also on the record by admission: the '053 specification itself concedes that several starting materials are "not a part of this invention" — 7-chloro-5-phenyl-3H-1,4-benzodiazepin-2(1H)-one 4-oxide, 7-nitro-5-phenyl-...-one, 7-chloro-5-(2-fluorophenyl)-...-one (Example 7), and the aminobenzophenone chemistry. Those admissions confirm the core is old.

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3. Level of ordinary skill in the art (Graham factor 2)

A Ph.D. or M.S. medicinal chemist with 2–5 years' experience in heterocyclic/CNS drug synthesis, or a B.S. chemist with several years' bench experience, working in a pharmaceutical company's benzodiazepine program in 1962–64. That artisan knew: (i) the 1,4-benzodiazepine ring system and its CNS utilities (R1); (ii) that position 1 is the readily alkylated, synthetically accessible site — deprotonate with NaH/NaOMe and treat with an alkyl halide (R2, R3); (iii) that the 5-aryl group tolerates o-halo substitution (R3); (iv) that trialkylaminoalkyl halides (Me₂NCH₂CH₂Cl, Et₂NCH₂CH₂Cl, Me₂N(CH₂)₃Cl) are commodity alkylating agents whose purpose is to introduce a salt-forming, water-solubilizing basic side chain; and (v) that 4-oxides reduce to the corresponding benzodiazepines and that N-oxides/3-oxy compounds interconvert (R4).

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4. The differences between the claims and the art (Graham factor 3)

Distilled to the Markush categories (per the earlier claim analysis):

There is no new element in the claims. Every claim element — the nucleus, the 5-aryl/2-haloaryl group, the 1-position alkylation site, the aminoalkyl halide, the amine displacement, the 3-oxy oxidation state, the salts — is individually old. The claimed subject matter is a recombination.

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5. Specific § 103 combinations and the motivation to combine

Under KSR, the motivation need not be found in the references themselves; it may come from "the background knowledge possessed by a person having ordinary skill in the art," from "design incentives and other market forces," or from the fact that the variation is "obvious to try" where "there are a finite number of identified, predictable solutions."

Combination A — R2 (or R3) in view of the aminoalkyl-halide art, and optionally R1

Yields: claims directed to 1-(aminoalkyl)-5-phenyl-3H-1,4-benzodiazepin-2(1H)-ones (B = carbonyl, R = H, acyclic dialkylamino). The single most powerful combination.

Motivation (four independent lines, any one sufficient):

1. Same field, same problem, same inventors, same assignee. R2 and R3 are Roche's own disclosures of the 1-position as a tolerated, easily functionalized site on the identical nucleus for the identical utilities (sedative/anticonvulsant/muscle relaxant).
2. The side chain's known function. Introducing a 2-(diethylamino)ethyl group onto a CNS-active N-heterocycle to confer water-soluble salt formation and altered tissue distribution was a standard medicinal-chemistry maneuver (the phenothiazine, antihistamine and antidepressant scaffolds all use exactly this -CH₂CH₂NR₂ handle). The '053 patent itself relies on this (the exemplified maleate/dimaleate/hydrochloride salts are marketed for their solubility). Using a known derivatization technique for its known purpose, on a known substrate, at a known reactive site, is the paradigm KSR case.
3. The reaction is the same reaction already in R2. R2 teaches NaOMe/NaH deprotonation of the lactam NH followed by alkyl halide quench. The '053 Examples 4–7 use precisely this: "sodium methoxide in methanol," the sodio salt of 7-chloro-5-phenyl-3H-1,4-benzodiazepin-2(1H)-one, then "a toluene solution of … 2-chloro-N,N-diethylethylamine." A POSA would not even need to combine references to reach the process claims — R2 is the process, with a different alkylating agent that is a commercially available commodity.
4. "Obvious to try." The universe of candidates was a finite, enumerated set: 1-alkyl halides (R2), 1-hydroxyalkyl, and 1-aminoalkyl halides. Where a skilled artisan has "a finite number of identified, predictable solutions," and the prior art gives a "reasonable expectation of success" — here, essentially certain success, since the reaction is documented on the same substrate — the variation is obvious as a matter of law.

Dependent-claim refinement: the claim's express preference for R₁ = R₂ = lower alkyl (the specification's own "preferred embodiment") is itself an admission that the diethylamino species is the obvious choice from the claimed genus.

Combination B — R3 in view of the standard benzophenone/anthranilate building blocks

Yields: the 5-(2-fluorophenyl) claims (the flurazepam family).

Motivation: R3 already discloses 2-halo-substituted 5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-ones made from the corresponding 2-amino-2′-halobenzophenones. The '053 specification's own Example 7 builds 7-chloro-5-(2-fluorophenyl)-3H-1,4-benzodiazepin-2(1H)-one from o-fluorobenzoyl chloride + p-chloroaniline — a routine Friedel–Crafts/benzophenone route — and expressly disclaims inventorship of it. Ortho-fluorine is the canonical electron-withdrawing/ortho-effect substituent used throughout the benzodiazepine SAR work of 1962 (and it is the pattern that recurs in flurazepam, fludiazepam, and later flunitrazepam). Selecting o-F from the disclosed halo set is a predictable, small-subset selection. In re Peterson / In re Roslak style limited-selection reasoning applies: the selection is from a small class for its known property.

Combination C — R4 in view of R2/R3

Yields: the R₃ = hydroxy and lower alkanoyloxy (acetoxy) claims, and the claimed acylation/hydrolysis process steps.

Motivation: R4 discloses 1-acyl-3-acyloxy benzodiazepinones, their hydrolysis with HCl/HBr to the 3-acyloxy species, and further hydrolysis to the 3-hydroxy compound. The '053 specification recites the mirror-image chemistry: "reaction … with an anhydride of a lower alkanoic acid, e.g. acetic anhydride," followed by "treatment … with an alkali metal hydroxide … or a mineral acid" back to the 3-hydroxy. Both directions were documented in the art before Feb. 11, 1963. This combination is nearly a verbatim anticipation of the process claims and makes the product claims obvious.

Combination D — R2/R4 in view of standard hydrogenation

Yields: the B = methylene (2,3-dihydro-1H-1,4-benzodiazepine) claims and the 4,5-dihydro / N-4-substituted claims.

Motivation: the '053 specification's own Example 9 hydrogenates a 4-oxide over Raney nickel to the corresponding 3H-benzodiazepin-2-one, and Example 27/28 hydrogenates over platinum oxide to the 4,5-dihydro series, which is then N-4 methylated (Example 29) and N-1 aminoalkylated (Example 26). Catalytic hydrogenation of benzodiazepine N-oxides/imines and subsequent N-alkylation are standard transformations fully within the artisan's repertoire (R4 also teaches N-deacylation). A 4-substituted claim that follows from reducing a known 4-oxide and alkylating the resulting secondary amine requires no inventive insight.

Combination E — R6 (or the phenyl→pyridyl bioisostere doctrine) in view of R2

Yields: the 5-pyridyl claims.

Motivation: pyridyl-for-phenyl is a textbook bioisosteric replacement used to alter basicity, solubility and metabolic stability; the artisan would have expected the 5-pyridyl analogs to retain the benzodiazepine pharmacology because the 5-aryl group is tolerated across a wide range (phenyl, o-halo-phenyl, etc.). Caveat: R6's March 1964 publication date places it after the '053 filing; if the pyridyl claims are supported in the 1962/1963 CIP parents, R6 is not available, and the combination must rest on the bioisostere rationale plus R1/R2/R3. If they are not supported in the parents, the analysis flips and R6 becomes highly relevant. This is the cleanest example of why the CIP-support question drives the outcome.

Combination F — the intermediate claims (Formula IV/V)

Yields: claims to the 1-(ω-haloalkyl)-benzodiazepinones and to the process of making them by reacting the sodio derivative with X-CₙH₂ₙ-X′.

Motivation: the '053 specification names 1-bromo-3-chloropropane, 2-bromoethyl chloride and 1-bromo-4-chlorobutane as the reagents — all three were known, commercially available α,ω-dihaloalkanes. Using a dihaloalkane to install a known haloalkyl tether at the N-1 site opened by R2/R3 is the § 102(b) statutory-bar-date reaction of a known compound with a known reagent. Because the intermediates' sole disclosed utility is as precursors to the (obvious) final products, they add nothing inventive; an intermediate whose structure is suggested by, and whose use is dictated by, an obvious end product is prima facie obvious. The patent's own statement that these compounds are "useful as anticonvulsants as well as … intermediates" does not create a separate invention — the anticonvulsant utility is the same utility as the genus in R1.

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6. Secondary considerations and the strongest non-obviousness arguments

The patent owner's best arguments, and my assessment:

1. Unexpected results / no teaching that N-1 aminoalkylation would give a hypnotic rather than an anxiolytic. Weakly supported. The specification contains no comparative pharmacological data against close analogs, and no data showing that the 1-aminoalkyl group produced an unexpected type or magnitude of activity. Where the specification shows nothing unexpected, the "unexpected results" argument is unsupported by the record (cf. In re Soni — unexpected results must be shown to be commensurate in scope with the claims, and here they are not shown at all).
2. Commercial success (DALMANE / flurazepam). Established in the earlier section: the '053 patent covered flurazepam HCl, the active in Roche's DALMANE, and Roche's enforcement of it produced Roche Prods., Inc. v. Bolar Pharm. Co., 733 F.2d 858 (Fed. Cir. 1984). This is genuine evidence of commercial success and of copying by a competitor — the classic secondary-consideration pairing. But it fails on nexus: the claims at issue are the broad genus, and the success is attributable to one species; moreover, the reason for the product's success (Roche's marketing, the 1980s hypnotic market, the water-solubility of the salt) is not shown to be caused by the inventive difference over R2/R3 (a 1-aminoalkyl-vs-1-methyl distinction). Under Ormco / Wm. Wrigley, the nexus must be to the claimed invention as a whole, and DALMANE's success does not establish the patentability of, e.g., a 5-(2-chlorophenyl)-piperidinoethyl species.
3. Long-felt need. Artisans had sought improved hypnotics/solubilized benzodiazepines since chlordiazepoxide (R1, 1959) — but the reference art (R2, R3, R4) shows the field was moving rapidly and successfully toward exactly these modifications in 1962, which undercuts (rather than supports) a long-felt-need narrative.
4. Teaching away. I found no reference teaching away from N-1 aminoalkylation, from o-fluorophenyl, or from any claimed element. Notably, the inventors' own '053 specification admits the N-oxide was not essential and could be removed — i.e., the art pointed toward simplifying and varying the molecule.
5. § 103(c)/common ownership (modern analysis). As noted in §1.2, this cannot rescue the claims: the two strongest references (R1 = 1959 patent; R3 = Nov. 1962 § 102(b) print publication) are not § 102(e)-only art and are outside any common-ownership exception.

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7. Claim-by-claim strength assessment

Net: the observed distribution is exactly the pattern one expects of an incremental, obvious genus patent in a field of intense, predictable structural modification: the broad claims are the most vulnerable, and the only claims with plausible survival are the narrow species claims read on flurazepam itself — and even those are exposed to a KSR "obvious to try" attack under Combinations A+B because the artisan had a finite set of 1-aminoalkyl groups and a finite set of 5-aryl groups, with a reasonable expectation of success grounded in the identical reaction described in R2.

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8. Explicit uncertainty flags

1. ⚠ The "Prior Art section" you pointed me to contains no references. It has only keyword tags and the 1964-02-11 prior-art date. I did not fabricate an examiner citation list. If you can supply the patent's "References Cited" table (or the file wrapper), the analysis should be re-run with the actual art — my selection of R1–R7 is my own, chosen for relevance, not the examiner's.
2. Unverified reference content: R5 (US 3,116,203 / 3,123,529 / 3,203,990) and R7 (US 3,136,815) are supported only by citation strings in third-party documents (a Chinese-language specification and a later patent's "References Cited" list). I have not read their claims or specifications. Do not treat my characterizations as established.
3. ⚠ Date contradiction to flag against my own earlier work: R6 (Fryer, Schmidt & Sternbach, J. Pharm. Sci. 53, 264 (1964)) is cited in the modern literature with a March 1964 date — i.e., after the Feb. 11, 1964 filing. If accurate, R6 is not § 102(a)/(b) prior art for this patent and cannot be used in Combination E as written. Anyone relying on Combination E must confirm the exact issue date against the printed journal.
4. Claim-level precision is unavailable (OCR corruption, as flagged in the earlier section). The category-level mapping in §4–§7 should not be treated as a claim chart.
5. CIP benefit is unverified from the record. I have assumed the parents (Ser. Nos. 176,901 and 259,753) support the core 1-aminoalkyl-5-phenyl genus. I have not compared the parents' disclosures to the '053 claims. The pyridyl and possibly the 2-fluorophenyl sub-genera are the categories most at risk of losing the earlier date — and thereby most exposed to art dated Feb. 1963–Feb. 1964.
6. My confidence in the dates of R1 and R2: R1's 1959 issuance and R2's Nov. 5, 1963 issuance are corroborated by two independent secondary sources each (search results above), but I did not open the original documents. R2 in particular is only § 102(e) (or § 102(a)) art for this patent, not § 102(b) art — its availability therefore depends on the invention-date question, which is a factual matter I cannot resolve from the text I have.

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Sources relied on

• https://patents.google.com/patent/US3299053A/en (authoritative full text supplied)
• https://patents.google.com/patent/US3109843 (R2)
• https://patents.google.com/patent/US3176009 (R4)
• https://ptacts.uspto.gov/ptacts/public-informations/petitions/[1557269](/patent/1557269)/download-documents (Cartt et al. "References Cited" list: 3,109,843 Reeder 11/1963; 3,136,815 Reeder 6/1964; 3,296,249 Bell 1/1967; etc.)
• Ullmann's Encyclopedia of Industrial Chemistry, "Hypnotics and Sedatives (N05C)" — cites "Roche, (1963) US 3109843, USA-prior.1962" and "Roche, (1967) US 3299053, USA-prior.1964"
• Sternbach et al., J. Org. Chem. 27, 3788 (1962) (R3), via https://pubs-acs-org.../acs.oprd.3c00327 and the Wikipedia "Diazepam" bibliography
• Fryer, Schmidt & Sternbach, J. Pharm. Sci. 53, 264 (1964) (R6), via the antidepressants/antipsychotics/anxiolytics bibliography
• https://patentimages.storage.googleapis.com/0a/1b/a3/596de37a43952a/CN1315963A.pdf (R5 citation strings)
• Roche Prods., Inc. v. Bolar Pharm. Co., 733 F.2d 858 (Fed. Cir. 1984) (secondary-consideration and commercial-success context, per the earlier litigation section)