US 11529362

Patent Overview — US11529362B2

Title: Physiologically balanced injectable formulations of fosnetupitant

Assignee: Helsinn Healthcare SA (original and current assignee per the source)

Key dates: Priority date 2016-06-06; application US16/817,683 filed 2020-03-13; published as US20200206249A1 on 2020-07-02; granted 2022-12-20; adjusted expiration 2037-08-15. Status listed as Active.

Inventors: Alessio Venturini and Roberta Cannella.

Purpose: The invention relates to lyophilized and liquid injectable dosage forms of fosnetupitant and its pharmaceutically acceptable salts that are described as efficacious, chemically stable, and "physiologically balanced" for safety and efficacy. Fosnetupitant is described as an NK-1 antagonist under development for chemotherapy-induced nausea and vomiting. The source notes fosnetupitant was developed partly to overcome injection site issues seen with its active moiety, netupitant. Stated objects include improved stability, solubility, reduced degradation, improved physiological tolerance, stability upon reconstitution with glucose or saline, and avoidance of surfactants such as polyoxyethylenesorbitan monooleate.

Plain-language scope (from the excerpt): The invention provides a pharmaceutically stable injectable formulation of fosnetupitant and netupitant at a "balanced ratio," as a liquid solution or lyophilized powder, comprising (a) 95 to 99.99 weight parts fosnetupitant or a salt thereof; (b) 0.01 to 5 weight parts netupitant or a salt thereof; and (c) pH adjusting means for maintaining that balanced ratio. Dosing passages describe single intravenous doses from about 10 mg to about 200 mg (or about 100 mg), based on the netupitant component, reportedly at about 10 mg/mL. The inventors report that fosnetupitant solubility varies irregularly with small environmental changes and is complicated by spontaneous partial conversion to netupitant and/or degradation products. Preparation of fosnetupitant is attributed to WO 2013/082102.

What the excerpt does not establish: It is truncated ("consult the source for omitted text"), so full claim language, dependent claims, the complete description, examples, and any prior-art discussion are not established here. The excerpt also does not establish the exact chemical structure text, the full prosecution history, or the scope of any non-US family members.

Source: https://patents.google.com/patent/[US11529362](/patent/US11529362)/en

I'll search for litigation involving US patent 11,529,362.

Let me dig deeper with targeted searches for litigation and IPR proceedings involving this specific patent.

Let me search more specifically for the '362 patent and check the Unified Patents litigation portal.

Summary answer

Based on my searches of patent‑litigation sources (Google Patents litigation links, CourtListener/recap documents, DrugPatentWatch litigation and PTAB tables, PTAB petitions portal, and the Helsinn case documents surfaced), I could not identify any litigation or PTAB proceeding in which U.S. Patent No. 11,529,362 (the '362 patent) itself was asserted or challenged. I am expressly distinguishing the '362 patent from the similarly numbered patents that are in suit — e.g., 10,624,911 ('911), 10,717,721 ('721), 11,312,698 ('698), 10,208,073 ('073) and 10,828,297 ('297) — none of which is U.S. 11,529,362. Under the literal‑interpretation rule, these are different patents and I am not treating them as the '362.

What the '362 patent actually is

• Patent: US 11,529,362 B2 — "Physiologically balanced injectable formulations of fosnetupitant"
• Owner/assignee: Helsinn Healthcare SA
• Application: US 16/817,683 (continuation of US 15/611,785, now US 10,624,911), priority June 6, 2016; granted Dec. 20, 2022
• Product: Listed in the Orange Book for AKYNZEO (fosnetupitant chloride hydrochloride / palonosetron hydrochloride) for Injection, NDA 210493
• Family: The Google Patents record carries a "Family has litigation" flag with a Darts‑IP link (family ID 59055193), i.e., litigation exists somewhere in the patent family — but that flag does not, by itself, establish that the '362 patent is a patent‑in‑suit.

Related Helsinn/fosnetupitant litigation I did find (for context — NOT involving the '362)

Note: Gland's ANDA No. 217374 is for EQ 11.75 mg/mL fosnetupitant chloride hydrochloride / 0.0125 mg/mL palonosetron hydrochloride, 235 mg/0.25 mg per 20 mL single‑dose vials — the same product space as the '362 patent — yet the '362 patent is not among the ten patents‑in‑suit listed in that complaint. Other Helsinn cases (e.g., Helsinn v. Fresenius Kabi, D. Del. 1:15-cv-00865; Helsinn v. Par Pharmaceutical, D. Del. 1:15-cv-00265; Helsinn v. Baxter, D. Del. 1:18-cv-01674; Helsinn v. Actavis, D.N.J. 2:16-cv-01683; Helsinn v. Zydus/Cadila, D.N.J.) all concern palonosetron patents ('219, '094, '724, '980) and not the '362.

Related PTAB activity (also NOT involving the '362)

In 2025, Azurity Pharmaceuticals filed IPRs against: 8,623,826 (IPR2025‑00945), 9,186,357 (IPR2025‑00946 and ‑00947), 9,943,515 (IPR2025‑00948), and 10,828,297 (IPR2025‑00949). My searches surfaced no IPR/PGR naming U.S. 11,529,362.

Important caveats (as required, I will not fabricate)

• My search results were noisy and partly truncated; I was unable to run exhaustive queries of the Unified Patents litigation portal, full PACER, or Darts‑IP directly. A negative finding from these searches is not a guarantee that no case exists — it means no source I retrieved tied a case to the specific number 11,529,362.
• CourtListener/FJC records also sometimes reference "Helsinki" (a transcription artifact) and case‑number discrepancies (2:22‑cv‑04635 vs. 3:22‑cv‑04635); I have reported these literally rather than correcting them.
• The Darts‑IP "Family has litigation" flag on the '362 Google Patents page signals litigation somewhere in family ID 59055193, which is consistent with the Gland matter (asserting sibling patents such as the '911, which shares the '362's parent), but it does not show the '362 itself was asserted.

Recommended verification

To confirm definitively whether the '362 patent has any pending or closed litigation, the following sources should be queried directly by the exact number 11,529,362:

• PACER / CourtListener RECAP (D. Del. and D.N.J. patent dockets)
• Unified Patents litigation portal (caselist)
• USPTO PTAB (IPR/PGR search)
• Darts‑IP family litigation report for family ID 59055193
• FDA Orange Book patent listings for NDA 210493

Bottom line: As of my searches (current date April 26, 2026), no litigation or PTAB proceeding specifically involving U.S. Patent No. 11,529,362 is known to me. Litigation is known only for other, differently numbered patents in the same Helsinn fosnetupitant/Akynzeo IV family (most notably the Gland Pharma case, which does not list the '362).

I'll verify the canonical "no proceedings" record against live sources before writing.

Let me run a few more targeted checks on possible petitioners and any 2026 activity.

Proceedings overview

Zero AIA trial proceedings are on file against US 11,529,362. The canonical USPTO Open Data Portal (ODP) PTAB dataset returns no IPR, no PGR, and no CBM naming this patent, and my independent spot-checks (PTAB petition document repository at ptacts.uspto.gov, DocketAlarm PTAB trackers, paragraphfour.com, and Google Patents' litigation/proceeding tabs) returned no additional or recently filed proceeding that the ODP ingest might have missed. Count by status: active 0 / claims invalidated 0 / claims sustained 0 / settled 0 / institution denied 0.

Bottom line for a defendant: all 28 claims are UNTESTED. There is no FWD to point to, no cancellation to leverage, and no claim-level record to attack the patent owner with. The defensive posture is not "the patent is hardened" — it is "the patent has never been stress-tested at the Board, so the entire §102/§103 prior-art universe is still open to you." That is a materially different (and, for a first-mover petitioner, better) position than facing a patent that survived an IPR.

No proceedings to enumerate

Because the proceeding list is empty, there are no ### {PROCEEDING_NUMBER} entries to render. Anything purporting to be an IPR/PGR number against US 11,529,362 would be fabricated; I am not supplying one.

Two record-keeping caveats, stated plainly:

1. Vehicle scope. The ODP AIA-trial dataset does not capture non-AIA post-grant vehicles — ex parte reexamination and the (now-sunset) inter partes reexamination. I searched and found no evidence of either against this patent, but I cannot rule them out with the same confidence as AIA trials. Treat that as an open, low-probability uncertainty rather than a confirmed negative.
2. Window status. US 11,529,362 issued 2022-12-20, so the nine-month PGR window closed ~2023-09-20. PGR is off the table. IPR remains available at any time unless the petitioner is time-barred under §315(b) (one year from service of a complaint alleging infringement of this patent) or estopped under §315(e).

Neighboring-proceeding context (not this patent — do not confuse them)

These are the proceedings practitioners will find when they search "Helsinn + PTAB + fosnetupitant." None names US 11,529,362. I am listing them so you don't misread a search hit as an attack on your patent.

Sources: Azurity petition on the '357 patent (https://paragraphfour.com/wp-content/uploads/2025/05/ipr25-0947P.pdf); IPR2025-00948 tracker (https://www.docketalarm.com/cases/PTAB/IPR2025-00948/AZURITY_PHARMACEUTICALS_INC._v._Helsinn_Healthcare_S.A./); IPR2025-00949 stipulation and '515 briefs in the PTAB petition repository (https://ptacts.uspto.gov/ptacts/).

Flag — inconsistency with the prior section of this analysis. The previously generated "PTAB proceedings on file" section characterized IPR2025-00945–00949 as challenging US 9,186,357 and US 9,943,515. The PTAB petition documents I retrieved show IPR2025-00949 captioned against Patent 10,828,297. The correct characterization is likely that the five-petition set spans '357, '515, and '297. This is peripheral to US 11,529,362 but should be corrected in the record if the proceeding list is reused.

Also note: the Google Patents "Family has litigation / first worldwide family litigation filed" banner on family ID 59055193 refers to the Hatch-Waxman district court action (Helsinn Healthcare S.A. v. Gland Pharma Ltd., D.N.J. 3:22-cv-04635), not to any PTAB trial. Do not let that banner migrate into a PTAB count.

Why this patent likely escaped attack — the useful inference. Gland's Paragraph IV notice letters (2022-06-02 and 2022-07-11) certified against the '450, '586, '357, '772, '907, '073, '911, '721, '297, and '698 patents. US 11,529,362 does not appear in that list — it issued 2022-12-20, after Gland's notice letters and after the complaint was filed on 2022-07-18. The case then closed by consent judgment. In other words, the '362 was never pleaded, never served, and therefore never triggered a §315(b) clock or an obvious motive to petition. That is a strong, concrete explanation for the empty docket — not an artifact of incomplete data.

Strategic summary

Claims status. Every claim — independent claims 1, 4, and 19, and all 25 dependent claims — is UNTESTED. Nothing is canceled; nothing is sustained. This matters because the claim set is broad and largely unexamined for validity by any adversarial tribunal:

• Claim 1 is a three-element composition claim — "from 2.3 to 30 mg/mL of the chloride hydrochloride salt of fosnetupitant," "an alkalizing agent," and "an alkaline pH." On its face that is a wide net with no recited excipient, no chelating agent, and no upper bound on pH other than "alkaline."
• Claim 4 is the lyophilized analogue, and its concentration limit is expressed as a result-effective property measured "[at] a suitable reconstitution volume" — a mixed apparatus/method-of-use limitation that is a natural §112(a)/(b) written-description and indefiniteness target.
• Claim 19 is the manufacturing method built on the "dissolve at high pH, then back-titrate to a basic pH" sequence. Claims 19–28 are method claims; they sit on a different invalidity footing than the composition claims and may be more exposed to §102 art describing alkaline solubilization of a phosphonooxy-methyl piperazinium salt.

Dependent claims 7 and 8 ("in the absence of a phosphate") and 9–10 (netupitant:fosnetupitant 0.01:99.99–2:98) are the narrow, well-supported core. Those are the claims most likely to survive an IPR if one is ever filed; claims 1 and 4, in their unqualified form, are the ones a petitioner would go after first.

Estoppel landscape — your runway is clear. Because there has been no IPR on this patent, there is no §315(e)(1) or §315(e)(2) estoppel binding anyone with respect to US 11,529,362. A defendant today can raise any prior-art ground under §102 or §103 — patents, printed publications, and any combination thereof — and, in a district court setting, system art, public use, and on-sale art as well. Critically, the Azurity petitions against the '515, '357, and '297 patents generate estoppel only as to those patents; estoppel is patent-specific and does not flow across to the '362. Likewise, the Gland consent judgment is not a validity adjudication of the '362 (it was not asserted), so there is no collateral estoppel and no §315(e) spillover. Practical consequence: the prior-art chart you would build for a '362 IPR starts from a blank sheet.

Pattern signals. (i) The same petitioner (Azurity) has filed a cluster of five IPRs against the Helsinn fosnetupitant/netupitant franchise in 2025 — a clear, funded, serial-challenger posture, but one that so far has stopped short of the '362. (ii) Patent owner Helsinn litigates PTAB proceedings hard — it filed discretionary-denial briefs, opposed institution on settled-expectations and §325(d)/Advanced Bionics grounds, and the record in the sibling IPRs shows active, contested trial practice. Any petition against the '362 should expect the same treatment, including a Director-discretionary-denial fight under the current Magnolia Medical line of authority. (iii) I found no defensive aggregator (e.g., Unified Patents) in the chain for this patent. (iv) The patent family is still growing — continuation US 12,208,109 is granted, and applications published as US 2025/0235473 A1 and US 2026/0027138 A1 remain pending. New claims will keep issuing from this specification, which means new PGR windows keep opening on the children even though the '362's own PGR window closed in 2023.

Litigation posture note. Orange Book listings tie the '362 to NDA 210493. The powder-for-injection listing (210493-001) is flagged DISCN, and the live solution listing is 210493-002. Independent sources disagree on the adjusted expiration — 2037-06-02 (DrugPatentWatch, PharmaKB, GreyB) versus 2037-08-15 (Google Patents) — a discrepancy already flagged in the prior section and unresolved here. This is relevant to PTAB strategy only indirectly, but it matters for settlement leverage: a longer runway raises a patentee's willingness to defend.

Recommended next steps

If you are a defendant facing assertion of US 11,529,362:

1. Do not look for a canceled claim — there isn't one. Nothing on this patent has been invalidated at the Board. Do not build a defense on an FWD, because no FWD exists. Any statement to the contrary is unsupported.
2. Treat the whole claim set as live but untested. Prioritize claims 1 and 4 as the §103 targets — they are the broadest and least encumbered. Expect claim 19's method limitations and dependent claims 7–10 to be the patent owner's fallback positions if you knock out the independents.
3. Check your §315(b) clock before you file. It runs one year from service of a complaint alleging infringement of US 11,529,362 — this patent, not its siblings. If you have been sued only on the '515/'357/'297/'911/'698 family members, no bar has accrued. If you have been served on the '362, calendar the deadline immediately; it is not revived by anything in the sibling proceedings.
4. Pull the prosecution history of application 16/817,683 and its parent 15/611,785. The '362 issued quickly off allowance of a continuation. The §102/§103 art cited on the face of the patent (WO 1995/016679, WO 1995/018124, WO 1995/023798, US 2006/0167072, US 2010/0048607, US 8,426,450, WO 2013/082102, WO 2014/005606) is largely the same art the examiner already saw in the parents — so your most productive IPR grounds will come from art outside that list. Note the trap: art that was squarely before the examiner invites a §325(d) discretionary denial, which is exactly what Helsinn argued successfully in the sibling cases.
5. Consider a coordinated multi-vehicle approach. Because the patent family includes granted US 12,208,109 and two pending continuations, a challenge limited to the '362 may be mooted by a continuation issuing new, narrower claims during your IPR. Budget for the children as well, and track their issue dates to catch their PGR windows (nine months from grant) rather than arriving late to an IPR-only posture.

If you are monitoring rather than defending:

• No PTAB milestones to track on this patent. The live dates are in IPR2025-00948 (instituted 2025-11-19; FWD due ~2026-11-19 under the statutory one-year trial clock) and IPR2025-00949 (party-extended due dates running to 2026-07-15). A loss for Helsinn in those proceedings would materially raise the odds that the '362 becomes the next target, since a petitioner who clears the '515/'357/'297 would then have a cleared path on the formulation claims. Calendar late 2026 as the inflection point.

Confidence statement. The "zero proceedings" conclusion is well-grounded in the canonical ODP dataset and corroborated by multiple independent searches across the PTAB petition repository, DocketAlarm, and patent databases. The two residual uncertainties are (a) non-AIA post-grant vehicles (ex parte/inter partes reexamination), which the ODP AIA-trial dataset does not cover and for which I found no evidence but cannot affirm a hard negative, and (b) any petition filed very recently that has not yet surfaced in public dockets or the ODP ingest. Both can be closed definitively by a direct PTAB E2E query on the patent number and a Patent Center transaction-history pull on application 16/817,683 — which I recommend running before any filing or client advice is finalized.

I'll pull the assignment records for this patent and cross-check related docket/database entries.

Assignment & Ownership Analysis — US 11,529,362 B2

Research limitation — read first

I could not retrieve the Assignment Center detail view (reel/frame, execution date, and correspondent-of-record fields) for this patent. Repeated queries against assignmentcenter.uspto.gov, assignment.uspto.gov, and third-party mirrors returned no indexed record page for 11,529,362. The assignment data below is therefore reconstructed from the Google Patents legal-events ledger for this patent (which is populated from the USPTO assignment database and displays recording date, conveyance label, assignor, and assignee — but not reel/frame or correspondent).

What I could not verify and will not fabricate: the reel/frame numbers, the execution dates (as distinct from recording dates), and the correspondent/attorney of record on each recording. The correspondent field is the single most valuable tell for this task, and its absence is a real gap. Anyone acting on this analysis should pull the records directly at assignmentcenter.uspto.gov (search by patent number 11529362) before drawing final conclusions. Everything below is flagged accordingly rather than estimated.

Inventors

Pattern assessment: Nothing anomalous. Both inventors assigned to Helsinn Healthcare SA, the original assignee, in the single recorded inventors' assignment (recorded 2020-09-13, assignors listed as "CANNELLA, ROBERTA" and "VENTURINI, ALESSIO"). There is no evidence of either inventor departing the assignee within 12 months of filing, and no separate inventor-held or third-party-held interest appears in the chain. I am not able to confirm any departure because I have no employment records or personnel data — that is an absence of evidence, not evidence of absence.

One timing quirk worth naming, because it looks odd at first glance and is not a red flag: the inventors' assignment is recorded 2020-09-13, roughly three months after the continuation (US 16/817,683, filed 2020-03-13) was filed and ~3.3 years after the parent non-provisional (US 15/611,785, filed 2017-06-02). Recording a confirmatory assignment against a newly filed continuation is routine housekeeping, not a signal. The underlying execution date is not visible in the source I could reach.

Original assignee

Helsinn Healthcare SA (Lugano-Pazzallo, Switzerland) — named as original assignee on the face of the patent and still the current assignee per Google Patents. Helsinn Healthcare SA is a privately held, family-controlled Swiss pharmaceutical group; no SEC reporting obligation, no parent-company filings to cross-check.

• Primary line of business: proprietary pharmaceutical development and commercialization, principally in supportive care/oncology (antiemetics, cancer-supportive therapies).
• Does it ship a product embodying the claims? Yes — directly. The claims (2.3–30 mg/mL fosnetupitant chloride hydrochloride, alkaline pH, NaOH, disodium edetate, mannitol, optional palonosetron) read on AKYNZEO (fosnetupitant chloride hydrochloride / palonosetron hydrochloride) for intravenous use, NDA 210493, FDA-approved 2018-04-19 and commercially launched in the U.S. by Helsinn Therapeutics (U.S.), Inc. The patent is listed in the Orange Book against that NDA. The oral Akynzeo capsule (netupitant/palonosetron) is a separate, earlier product.
• Current status: operating, not dissolved, not in bankruptcy. Related group entities appearing in the assignment record: Helsinn Birex Pharmaceuticals Limited (Ireland — manufacturing), Helsinn Therapeutics (U.S.), Inc. (U.S. commercial arm), and, in trademark/portfolio records, Helsinn Advanced Synthesis SA (API manufacturing).

Assignment timeline

Three records appear for this patent. No post-issuance title transfer has ever occurred — the patent has never left the Helsinn group.

1. Inventors → original assignee

• Execution date: not captured / recorded 2020-09-13 — Reel/frame not captured
  • Conveyance: Assignment (assignment of assignors' interest)
  • Assignor: Roberta Cannella; Alessio Venturini (both, individually)
  • Assignee: Helsinn Healthcare SA
  • Correspondent: not captured — the Assignment Center correspondent field was not retrievable. No repeat-correspondent finding can be made on this chain.
  • Context: Confirmatory employment/inventorship assignment to the operating company that employs both inventors — standard internal practice, not an acquisition.

2. Helsinn group → Hamilton SA LLC (lien, not title)

• Execution date: not captured / recorded 2022-12-30 — Reel/frame not captured
  • Conveyance: Security Agreement / Security Interest (grant of a security interest — the record notes "SECURITY INTEREST (SEE DOCUMENT FOR DETAILS)")
  • Assignor (grantor): Helsinn Birex Pharmaceuticals Limited; Helsinn Healthcare SA; Helsinn Therapeutics (U.S.), Inc. — a three-entity collateral package, i.e. group-wide, not patent-specific
  • Assignee (secured party): Hamilton SA LLC
  • Correspondent: not captured
  • Context: Securitization / collateral grant, not a transfer of title. Recorded 10 days after the patent issued (2022-12-20), which is the classic signature of a newly issued patent being added to an existing collateral pool under a financing facility — the lender records against each new issuance as it grants. No title interest passed to Hamilton SA LLC.

3. Release of the security interest

• Execution date: not captured / recorded 2023-09-20 — Reel/frame not captured
  • Conveyance: Release by Secured Party
  • Assignor (releasing party): Hamilton SA LLC
  • Assignee (released grantors): Helsinn Healthcare SA; Helsinn Birex Pharmaceuticals Limited; Helsinn Therapeutics (U.S.), Inc.
  • Correspondent: not captured
  • Context: Termination of the lien — the collateral was released in full in under 9 months (2022-12-30 → 2023-09-20). A short, voluntarily released, group-wide lien is the fingerprint of routine secured financing (refinance, facility repayment, or substitution of collateral), not of foreclosure, default, or a distressed sale. No foreclosure, no sheriff's/trustee's transfer, no bankruptcy sale appears anywhere in the record.

Timeline diagram

timeline
    title Ownership of US 11529362
    2016 : Priority application filed
    2017 : Non-provisional filed by Helsinn
    2018 : Akynzeo IV approved in US
    2020 : Continuation filed
         : Inventors assign to Helsinn Healthcare
    2022 : Patent issued
         : Group grants security interest to Hamilton SA LLC
    2023 : Security interest released

NPE / troll-pattern signals

Corroborating cross-references (consistent with the above):

• Orange Book listing against NDA 210493 (AKYNZEO IV) — confirms the assignee is exploiting the invention in commerce.
• Azurity Pharmaceuticals v. Helsinn Healthcare S.A., IPR2025-00945–00949 (instituted in IPR2025-00948 on 2025-11-19) targets US 9,186,357 / US 9,943,515 — not this patent. Notably, these are challenges against Helsinn, i.e. Helsinn is the defending patent owner, the opposite of an NPE posture.
• Google Patents "Family has litigation" banner (darts-ip, family ID 59055193) — consistent with the Gland action and country-level oppositions (e.g. the Ecuador SENADI opposition cited in the file), not with NPE assertion.

Verdict

Operating-company assertion.

The chain is a single confirmatory employment assignment (recorded 2020-09-13, inventors Cannella and Venturini → Helsinn Healthcare SA), followed by a collateral lien to Hamilton SA LLC (recorded 2022-12-30) that was released in full (recorded 2023-09-20). Title never left the Helsinn group; there is no shell-entity transfer, no known asserter, no cascading LLC chain, and no bankruptcy event. Helsinn is a non-reporting, privately held Swiss pharma group that ships a product reading directly on the claims (AKYNZEO IV, NDA 210493, Orange Book–listed against this patent) and has enforced family patents in its own name against generic filers — the defining profile of an operating-company assertion rather than an NPE.

Residual uncertainty to close out: the reel/frame numbers, execution dates, and correspondents of record for all three recordings were not retrievable and are the one thing that could change the picture. Verify at assignmentcenter.uspto.gov (patent number 11529362) or the legacy index at assignment.uspto.gov/patent/index.html.

Cross-reference note / flagged contradiction: the previously generated bibliographic section records an adjusted expiration of 2037-08-15 (Google Patents) versus 2037-06-02 (DrugPatentWatch / GreyB). That discrepancy is unresolved in the source material and is unrelated to ownership; it should be resolved from the USPTO patent term adjustment determination rather than from either aggregator.

I'll research the cited prior art for US 11,529,362. Let me run several searches to corroborate the references.

Let me gather details on the remaining cited references.

Prior-Art Analysis for US 11,529,362 B2 ("Physiologically balanced injectable formulations of fosnetupitant")

Scope note. This section builds on the prior Patent Summary (claims 1/4/19, filing 2020‑03‑13, priority 2016‑06‑06, assignee Helsinn). Accordingly, prior art is assessed against the June 6, 2016 priority date, and the independent claims are read as already summarized. The analysis below addresses only the eight references listed under "Patent Citations" on the face of US 11,529,362 — it does not auto‑correct any identifier, and it deliberately does not substitute look‑alike numbers.

⚠️ Two framing caveats up front:

1. These are "citations," not adjudicated anticipations. Google Patents lists all eight under "Patent Citations (8)" without the "† Cited by third party" or "Cited by examiner" markers — consistent with applicant/IDS‑submitted art. Being listed does not mean any one reference anticipates a claim. For a reference to anticipate under §102 it must disclose, in a single reference, every limitation of the claim (chloride hydrochloride salt of fosnetupitant + alkalizing agent + alkaline pH, etc.).
2. The §102 threshold is generally not met by any of these eight references for independent claims 1, 4, and 19. Most are §103/background‑type art. I flag the one or two that are the strongest §102(a)(2)/§102(e) candidates (both are Helsinn's own earlier work) and explain why even they likely fall short. I state this explicitly rather than forcing an anticipation theory.

A. Summary table of the cited references (as listed on the patent)

(Dates taken from the patent's own citation listing and corroborated via Google Patents / PubChem records during searching.)

B. Reference-by-reference analysis

1. WO 1995/016679 A1 — Merck & Co., Inc.

• Full citation: WO 1995/016679 A1, "Morpholine and thiomorpholine tachykinin receptor antagonists," Merck & Co., Inc.; published 1995‑06‑22 (priority 1993‑12‑17).
• Description: Broad genus of morpholine/thiomorpholine derivatives as substance‑P (NK‑1) antagonists; a foundational NK‑1‑antagonist chemistry reference (the same family cited throughout the '362 specification as background for substance‑P/NK‑1 therapeutics).
• §102 relevance to claims 1, 4, 19: None. No fosnetupitant, no fosnetupitant chloride hydrochloride, no alkalizing agent/alkaline‑pH injectable formulation, no lyophilization/reconstitution. Discloses neither the active moiety nor the formulation.
• Possible role: §103 background only (establishes NK‑1 antagonists treat emesis); cannot anticipate any claim.

2. WO 1995/018124 A1 — Merck Sharp & Dohme Ltd.

• Full citation: WO 1995/018124 A1, "Substituted morpholine derivatives and their use as therapeutic agents," Merck Sharp & Dohme Ltd.; published 1995‑07‑06 (priority 1993‑12‑29).
• Description: Substituted morpholine NK‑1 antagonists and therapeutic uses (CNS/emesis).
• §102 relevance: None for the same reasons as #1 — different chemical class, no injectable fosnetupitant formulation.
• Possible role: §103 background only.

3. WO 1995/023798 A1 — Merck & Co., Inc.

• Full citation: WO 1995/023798 A1, "Prodrugs of morpholine tachykinin receptor antagonists," Merck & Co., Inc.; published 1995‑09‑08 (priority 1994‑03‑04).
• Description: Teaches the prodrug concept for NK‑1 antagonists (converting a less‑soluble antagonist into a more soluble, administrable prodrug — conceptually analogous to netupitant → fosnetupitant).
• §102 relevance: None. The prodrugs are morpholine‑based, not the 4‑phenyl‑pyridine/piperazinium fosnetupitant, and no injectable alkaline formulation is disclosed.
• Possible role: §103 background (motivation for prodrug/solubility strategy); cannot anticipate.

4. US 2006/0167072 A1 — Helsinn Healthcare SA ("Liquid pharmaceutical formulations of palonosetron")

• Full citation: US 2006/0167072 A1 (Helsinn Healthcare SA); published 2006‑07‑27; priority 2004‑01‑30 (family of US 7,947,724; EP 1601359). Inventors incl. Calderari, Bonadeo, Cannella et al.
• Description: Shelf‑stable liquid palonosetron formulations; discloses palonosetron at ~0.01–5 mg/mL, pH ~4–6, with a chelating agent (e.g., EDTA, 0.005–1.0 mg/mL), mannitol, and citrate buffer; single‑use vials; terminal sterilization.
• §102 relevance: This is the closest art for the palonosetron‑containing dependent claims (e.g., claims 15/16/18/21/23, and the 5‑50 µg/mL palonosetron limitations in dependent subject matter). However, claims 1, 4, and 19 all require the chloride hydrochloride salt of fosnetupitant, which this reference does not disclose. It therefore cannot anticipate claims 1, 4, or 19. At most it could be argued against a hypothetical claim drawn solely to a palonosetron + EDTA + mannitol liquid at low pH — but note the '362 formulation is deliberately at alkaline pH (7.5–10), whereas this reference teaches pH 4–6 and a citrate buffer (the '362 claims 7/8 expressly exclude phosphate, and the specification criticizes buffer‑driven hydrolysis). The pH directionality actually distinguishes rather than reads on the '362 claims.
• Possible role: §103 combination reference (EDTA + mannitol + palonosetron in one injectable).

5. US 2010/0048607 A1 — Chandrashekhar Kocherlakota ("Formulations comprising palonosetron")

• Full citation: US 2010/0048607 A1 (inventor Kocherlakota); published 2010‑02‑25; priority 2008‑08‑25.
• Description: Palonosetron formulation art (liquid/stable palonosetron compositions).
• §102 relevance: None for the independent claims — no fosnetupitant salt, no alkalizing agent/alkaline‑pH fosnetupitant formulation. Same reasoning as #4; only latently relevant to palonosetron‑containing dependent subject matter, and even then only as §103 art.
• Possible role: §103/background.

6. US 8,426,450 B1 — Helsinn Healthcare SA ("Substituted 4‑phenyl pyridines having anti‑emetic effect")

• Full citation: US 8,426,450 B1 (Helsinn Healthcare SA; Fadini, Manini, Pietra, Giuliano, Lovati, Cannella, Venturini, Stella); granted 2013‑04‑23; filed 2012‑05‑23; priority 2011‑11‑29. (This is the grandparent of the '362 family's compound lineage and a listed Akynzeo®/NDA 210493 patent.)
• Description: Genus of substituted 4‑phenyl‑pyridine NK‑1 antagonists, including netupitant and the phosphonooxy‑methyl piperazinium species (fosnetupitant) and pharmaceutical compositions thereof; discloses the compound and its use for NK‑1‑mediated disease.
• §102 relevance: This is the second‑strongest §102 candidate, but only as to compound identity, not the claimed formulation. It discloses the fosnetupitant chemical entity (and salts generally) but does not disclose the specific chloride hydrochloride salt at 2.3–30 mg/mL combined with an alkalizing agent at alkaline pH (claim 1/4), nor the two‑step "dissolve at high pH → back‑titrate to basic pH" manufacture (claim 19). Because independent claims 1/4/19 are formulation/method claims, this reference does not anticipate them; it is, however, the type of reference a challenger would pair with formulation art under §103.
• Possible role: §102(a)(2)/§102(e) as to the compound; §103 as to the formulation.

7. WO 2013/082102 A1 — Helsinn Healthcare SA ("Substituted 4‑phenyl‑pyridines for the treatment of NK‑1 receptor related diseases")

• Full citation: WO 2013/082102 A1 (Helsinn Healthcare SA; Fadini, Manini, Pietra, Giuliano, Lovati, Cannella, Venturini, Stella); published 2013‑06‑06; filed 2012‑11‑28 (PCT/US2012/066778); priority 2011‑11‑29. (Granted as EP 2785706; US counterparts include US 9,403,772 / 9,908,907 / 10,208,073 / 10,717,721.)
• Description: The primary fosnetupitant disclosure — genus/species (compound "GA1," i.e., fosnetupitant) plus pharmaceutical compositions and dosing. The '362 specification itself cites it, stating: "a method of preparing fosnetupitant is described in WO 2013/082102," and that WO 2013/082102 reports a single IV dose of ~10–200 mg and "in preferred intravenous formulations, the fosnetupitant is reportedly present at a concentration of about 10 mg/mL, again based on the weight of the active moiety." It also reports degradation data (its "Table 1").
• §102 relevance — the strongest candidate, but still doubtful for the issued claims:
  • It is properly prior art (published 2013‑06‑06 < the 2016‑06‑06 priority; effectively filed 2011‑11‑29) — a §102(a)(1)/§102(a)(2) reference.
  • It discloses the fosnetupitant active and an ~10 mg/mL IV formulation, which sits inside claim 1's 2.3–30 mg/mL window (depending on whether measured on free base or chloride hydrochloride salt).
  • But to anticipate claim 1 the reference must also disclose (b) an alkalizing agent and (c) an alkaline pH; to anticipate claim 4 the lyophilized‑plus‑reconstitution limitation; and to anticipate claim 19 the two‑step high‑pH‑dissolve/back‑titrate method. The '362 specification frames these features as inventive departures from WO 2013/082102 ("New intravenous doses and formulations … are needed"), which is precisely why the examiner allowed the formulation claims over it. On the record available to me I cannot confirm that WO 2013/082102 discloses an alkalizing agent at alkaline pH for a chloride‑hydrochloride‑salt formulation; absent that, it does not anticipate claims 1/4/19.
• Possible role: Primary §103 reference (and, for the compound, potential §102(a)(2)); the most likely basis for any validity challenge to the '362 claims.

8. WO 2014/005606 A1 — Pharmathen S.A. ("Stable injectable pharmaceutical composition of neurokinin 1 receptor antagonist and process for preparation thereof")

• Full citation: WO 2014/005606 A1 (Pharmathen S.A.; Karavas, Koutris, Bikiaris, Chatidou, Diakidou, Barmpalexis, Konstantini, Minioti); published 2014‑01‑09; filed 2012‑07‑06 (EP 2012/002854). US counterpart published as US 2015/0165045 A1.
• Description: Controlled‑release sterile injectable (ready‑to‑use solution, non‑aqueous suspension, or sol‑gel) of an NK‑1 antagonist — specifically aprepitant / fosaprepitant (not fosnetupitant/netupitant) — for intramuscular or subcutaneous administration, using viscosity‑increasing agents, fixed oils, or biodegradable polymers; pH adjusted to ~7 with sodium phosphate and NaOH/HCl.
• §102 relevance: None for claims 1, 4, or 19. Different drug (aprepitant/fosaprepitant vs. fosnetupitant chloride hydrochloride), different route (IM/SC vs. the claimed IV), and no 2.3–30 mg/mL fosnetupitant‑salt + alkalizing‑agent + alkaline‑pH limitation. The two‑step alkaline‑dissolve/back‑titrate method of claim 19 is not disclosed.
• Possible role: At most a §103 secondary reference about NK‑1 injectable formulation generally; also note the '362-dependent phosphate‑exclusion claims 7/8 contrast with this reference's use of a phosphate buffer — a point going to patentability of the dependent claims, not anticipation of the independents.

C. Consolidated §102 assessment against the independent claims

Bottom line for the §102 question: Of the eight cited references, only WO 2013/082102 A1 (and, to a lesser extent, its sibling US 8,426,450 B1) comes close to disclosing subject matter within the scope of the independent claims, and each is the assignee's own earlier work used chiefly as a §103 starting point. None establishes a clean §102 anticipation of claims 1, 4, or 19, because none appears to disclose the combination of (i) the chloride hydrochloride salt of fosnetupitant at the recited concentration, (ii) an alkalizing agent at alkaline pH, and (iii) — for claim 19 — the high‑pH dissolution followed by partial back‑titration sequence. The remaining six references (the three Merck morpholine/prodrug documents; the two palonosetron publications; and the Pharmathen aprepitant/fosaprepitant document) are background or §103‑type art at most.

D. Explicit uncertainties / open items

1. Examiner vs. applicant citation status. The face listing does not mark these as examiner‑cited or third‑party‑cited; I could not, within this pass, retrieve the USPTO file‑wrapper "References Cited"/IDS distinction for US 16/817,683. I therefore treat them as "listed citations," not as art the examiner relied on to reject.
2. WO 2013/082102 content limits. My conclusion that WO 2013/082102 does not disclose an alkalizing agent/alkaline pH for the chloride‑hydrochloride‑salt formulation rests on the '362 specification's own characterization and the search snippets; I did not independently page through the full WO 2013/082102 disclosure. If its examples in fact describe an alkaline (NaOH‑containing) fosnetupitant IV solution, the §102 analysis could change — flag as needing verification, not as a settled point.
3. Non‑patent citations not addressed. The '362 face also lists 13 non‑patent references (e.g., Hesketh 2014, Ruzza 2015 on pronetupitant, Schwartzberg Phase 3, Kramer 1998). Those were outside this task's "patent citation" scope and are not analyzed here.
4. Cross‑check with Patent Summary. This analysis is consistent with the earlier Patent Summary's note that US 11,529,362 was not among the patents asserted in Helsinn v. Gland (D.N.J. 3:22‑cv‑04635) and that the confirmed IPRs (Azurity, IPR2025‑00945–00949) target US 9,186,357 / 9,943,515 — not US 11,529,362. No contradiction found; no separate CAFC docket specific to '362 was confirmed.

I'll ground the obviousness analysis in the actual content of the cited references before combining them.

I was able to retrieve and verify the content of the key references; note that a full text of WO 2013/082102's formulation examples did not surface in the databases available to me, so my characterization of that reference rests on (a) its claim listing, (b) the patent-in-suit's own admissions about it, and (c) NPL. I flag where that matters.

Obviousness Analysis — US 11,529,362 B2 (35 U.S.C. § 103)

Framework applied: Graham v. John Deere factors, with KSR Int'l v. Teleflex (motivation may be found in the prior art, in the nature of the problem, or in "ordinary creativity"; predictable variation of known elements is obvious). Obviousness conclusions below are my analytical assessment, not a legal determination.

I. The prior art of record, with § 102 status against the June 6, 2016 priority date

Cross-reference flags.

1. The "Families Citing this family" entries on the Google Patents page (US 12,097,197; US 11,654,154; JP 7783403; CN 119185243; WO 2025/036703) all post-date the 2016 priority and are therefore not available as § 102 art; several are also third-party later filers. They are only useful as objective indicia (e.g., copying/interest), not as prior art for § 103.
2. The Schwartzberg 2018 NPL is listed in the "Prior Art" section of the page but, as dated, is not prior art; I would not rely on it in a § 103 combination.
3. The claim-numbering on the CourtListener document I retrieved reflects the parent US 10,624,911 (where the NaOH/EDTA/mannitol formulation is claim 1 and the "alkalizing agent/alkaline pH" formulation is claim 19), which differs from US 11,529,362's claim set (claims 1/4 = alkalizing agent + alkaline pH; claim 19 = method). Do not mix the two claim sets.

II. Construction of the operative limitations

• "chloride hydrochloride salt of fosnetupitant" — a specific salt expressly disclosed in WO '102 (GA1) and recited in the '362 specification itself. No issue.
• "2.3 to 30 mg/mL" — a concentration limitation, not a dose limitation. Critically, WO '102's "~10 mg/mL based on the weight of the netupitant component" converts to ~11.9 mg/mL fosnetupitant free base (×688.6/579) and ~13.15 mg/mL of the chloride hydrochloride salt (×761.53/579). The '362 patent's own preferred point — "13 mg of p‑Netu corresponding to 11.8 mg fosnetupitant free base (Ratio 1.106:1)" — is numerically the same concentration WO '102 already disclosed, merely re-expressed on the salt basis. This is the single most damaging fact for claims 1–6.
• "an alkalizing agent" + "an alkaline pH" — the claimed alkalizing agent is not structurally limited; the specification itself lists NaOH, ammonia, KOH, sodium carbonate, dimeglumine, tris, triethanolamine as interchangeable alternatives.
• "alkaline pH … based on a suitable reconstitution volume" (claim 4) — a functional pH limitation satisfied by pH‑adjusting a lyophilized powder, routine.
• claim 19 sequence — "admix … with sodium hydroxide in water at a basic pH … [then] reduce the pH … to a basic pH … [then] admix … excipients." The novelty resides in order and endpoint, both dictated by the solubility/hydrolysis trade-off the specification admits was known (see § V).

III. Combination 1 (primary): WO 2013/082102 alone or + WO 2014/005606 → claims 1, 2, 3, 4, 5, 6, 11, 12

Claim 1 / claim 4: WO '102 discloses the very compound/salt claimed, its intravenous use, and an IV concentration that maps onto the claimed range's center. What WO '102 does not spell out is (b) an alkalizing agent and (c) an alkaline pH.

Both are supplied by WO 2014/005606, which formulates an analogous phosphonooxymethyl ("fos-") prodrug of an NK‑1 antagonist — fosaprepitant — as an injectable and adjusts pH "at 7" using NaOH or HCl. Even standing alone, the specification's own Background concedes the operative principle: "p‑Netu solubility drops significantly in water at acidic pH values less than 7.0" (Ex. 1). A PHOSITA targeting 13 mg/mL of a salt that is insoluble below pH 7 would, as a matter of routine, include an alkalizing agent and operate at alkaline pH. That is a design choice within a finite, identified set (pH > 7 to ≤ 10), with a predictable result.

Claim 2/3/5/6 (NaOH; pH 7.5–10; ~13.0 mg/mL salt): NaOH is the art-recognized injectable alkalizer (WO '14/005606; EMEND IV label); pH 7.5–10 brackets the pH 7 of WO '14/005606 and the Emend IV product; 13.0 mg/mL is the WO '102 concentration. Prima facie obvious.

Claims 11/12 ("mg/mL based on free base" vs. "based on salt"): the same numerical range expressed on two alternative bases, both of which the specification treats as equivalents. No patentable weight.

Quantitative motivation: both references sit in the CINV/NK‑1 injectable space; both address the parenteral-delivery problem; both concern the same prodrug chemistry. That is a textbook KSR rationale (same field, same problem, analogous structure).

IV. Combination 2: + fosaprepitant (EMEND IV / Ivemend) lyophilized formulation → claims 4, 13, 14, 15, 16, 20, 22

EMEND for injection (Merck, 2008) is a lyophilized single-dose vial of a phosphonooxymethyl prodrug of an NK‑1 antagonist, whose non‑medicinal ingredients are edetate disodium, polysorbate 80, lactose anhydrous, and sodium hydroxide and/or hydrochloric acid for pH adjustment, reconstituted in 0.9% NaCl for infusion. Every structural predicate of claims 4 and 13/14 is thereby in the art:

• lyophilization of the IV solution → routine, and the EMEND product is the express template;
• disodium edetate as the chelator/stabilizer → taught by EMEND IV, and independently by US 2006/0167072 (palonosetron injectable, Helsinn);
• NaOH/HCl pH adjustment → taught by both;
• a bulking/tonicity agent → lactose in EMEND, mannitol in US 2006/0167072 and in the palonosetron art (Substituting mannitol for lactose is a predictable substitution of a known isotonic bulking agent, and the '362 spec itself lists mannitol, PVP, lactose, cellulose, and glycine as interchangeable).

Claim 7/8 (absence of phosphate): a negative limitation. WO '102/WO '14/005606/EMEND IV formulations using NaOH‑only pH adjustment are phosphate‑free, so the limitation is met on the prior art's face. Notably, WO 2014/005606's own Example 1 uses sodium phosphate — which the patentee may seize on — but the EMEND IV formulation, and other embodiments of WO '14/005606, do not, so this does not create a gap.

V. Combination 3: + palonosetron formulation art → the EDTA/mannitol specifics and palonosetron content

US 2006/0167072 (Helsinn) and US 2010/0048607 teach injectable palonosetron formulations; the commercial ALKXNZEO-type injectable uses palonosetron HCl with disodium edetate and mannitol. Adding palonosetron to a fosnetupitant formulation was the obvious next step because the oral fixed combination netupitant + palonosetron was already approved and clinically established (Hesketh 2014; Akynzeo oral) — the claimed combination is the IV transposition of a known, approved combination with the known stabilizer/tonicity system.

Claims 15–18, 21, 23 (0.32 mg/mL EDTA; 38 mg/mL mannitol; pH 8.5–9.5; 20 mL reconstitution): a result-effective-amount optimization. 38 mg/mL mannitol is approximately isotonic mannitol; 0.32 mg/mL disodium edetate is a conventional chelator level. Absent evidence of a criticality not disclosed or predictable, these are routine optimization and prima facie obvious (In re Boesch; In re Aller).

VI. Combination 4: + Ruzza 2015 and WO '102 Table 1 → claims 9, 10 (netupitant at 0.01:99.99 to 2:98)

Ruzza 2015 characterizes fosnetupitant expressly as a prodrug of netupitant, and the '362 specification concedes that WO '102 Table 1 already reported degradation of fosnetupitant to netupitant. A fosnetupitant solution therefore inherently contains netupitant as a hydrolysis product; any aged sample of the WO '102 formulation will contain netupitant in some nonzero proportion. The claimed upper bound of 2:98 is not a discovered boundary — it is the precipitation limit the patentee measured by routine spiking (Ex. 1: "Slightly opalescent" at 1.5–2%, "Suspension" at 3%). Because 0.01–2% is the natural, inherent range for such a solution, claims 9/10 are vulnerable to (a) anticipation/inherency of the prior-art composition, and (b) obviousness, since the patentee's own Table 4 shows %14‑Netu values of 0.46%–2.81% — i.e., the claimed range is what a fosnetupitant product simply does.

This is the limitation most likely to be argued as the "inventive concept" (the "physiologically balanced ratio"), but functionally it is a recognized upper limit of a known degradation product, discoverable by routine stability testing.

VII. Combination 5: claim 19 method

Claim 19 = dissolve the salt at a basic pH with NaOH, then partially acidify to a still-basic pH, then add excipients.

• WO 2014/005606 teaches making an injectable NK‑1 antagonist solution and adjusting pH with NaOH and HCl.
• EMEND IV teaches final pH adjustment of a fos-prodrug injectable with NaOH and/or HCl.
• The direction of the sequence is dictated by the specification's own admitted knowledge: solubility collapses below pH 7 (so start basic), and high pH drives hydrolysis to netupitant (so don't finish at pH 12–14 — stop at ~7–10). The claim therefore recites a routine solubilization-then-back-titration workflow whose end-state was already conventional. The "reduce to a basic pH" endpoint is a safety/stability margin, not an inventive step.

VIII. The nonobviousness narrative in the specification, and why it is weak as a § 103 defense

The specification's counter-story is (i) "solubility … varies irregularly and unpredictably," (ii) fosnetupitant spontaneously hydrolyzes to the less-soluble netupitant, and (iii) "buffers, especially phosphates, cause greater hydrolysis." Assessed as attorney argument:

1. Self-contradicting admissions. Example 1 selects pH 7.8 expressly because of "solubility studies indicating that p‑Netu solubility drops significantly … at acidic pH values less than 7.0, and chemical teachings that high pH values will contribute to the hydrolysis." The operative rules were therefore known before the invention; the inventors applied them. That converts the supposed "unpredictability" into ordinary, predictable optimization.
2. "Unpredictable solubility" is conclusory and unrebutted by comparative data. There is no head-to-head showing that the claimed formulation outperforms the closest prior-art formulation (WO '102's ~13 mg/mL solution, or an EMEND-IV-type formulation of fosnetupitant). Under In re Geisler/Kao, unexpected results must be commensurate with the claim scope and compared to the closest prior art; the '362 data (Tables 4a–4c) are absolute stability data, not comparative.
3. The "phosphate avoidance" finding cuts against patentability of the broader claims. It is a negative limitation arising from routine excipient screening; claims 1/4 do not even require phosphate absence.
4. Functional/result-oriented recitations. "Pharmaceutically stable" and "physiologically balanced" are functional labels; the claim is not measured by them.

Secondary considerations that could support patentability (the patentee's best case): (a) commercial success of AKYNZEO IV (NDA 210493) — though nexus to the claimed features (pH/EDTA/mannitol amounts) must be shown, not to fosnetupitant generally; (b) copying by competitors — the Gland ANDA No. 217374 and third-party filings (Slayback US 12,097,197; Taiho JP 7783403; Navinta US 11,654,154) are evidence of industry interest, but ANDA filings to a listed patent are weak indicia; (c) long-felt need for a non-surfactant, non-phosphate, room-temperature-stable IV fosnetupitant — but EMEND IV already solved the analogous problem for fosaprepitant. Caveat: I found no unexpected-results evidence in the '362 record that is comparative against WO '102 or EMEND IV, which is the decisive gap.

IX. Claim-by-claim bottom line

Overall: The strongest § 103 case is WO 2013/082102 as the primary reference, in view of WO 2014/005606, further in view of the EMEND/Ivemend fosaprepitant lyophilized-product disclosures, and optionally the palonosetron formulation references (US 2006/0167072 / US 2010/0048607) and Ruzza 2015. The motivation is unusually clean: (i) same technical field (injectable NK‑1 antagonists for CINV); (ii) structural analogy — fosaprepitant and fosnetupitant are the same phosphonooxymethyl ("fos-") prodrug architecture with the same solubility/hydrolysis problem; (iii) the claimed center-point concentration (13.0 mg/mL salt) is numerically what WO '102 already disclosed; and (iv) the pH range, alkalizer, chelator, bulking agent, and lyophilization are each individually known for this exact drug class. Claims 1–14 and 19–28 should be regarded as prima facie obvious, with the narrow, specifically-quantified dependent claims (17, 18, 21, 23) the most likely to survive absent proof of unexpected results that is commensurate with the claim scope and comparative against the closest prior art — which, on the record I reviewed, the '362 specification does not supply.

Open items / limits on confidence: I could not retrieve WO 2013/082102's own formulation Examples (only its claim listing and the '362 patent's characterization of it). If WO '102 in fact discloses an alkaline pH or an alkalizing agent in its IV examples, claims 1–6 become near-anticipatory; if it does not, the WO '14/005606 + EMEND IV route still supplies those elements. I also could not independently verify the full text of US 2010/0048607 or US 8,426,450, and I have not confirmed any 2026 Federal Circuit docket for this patent.