US 9980944

I'll search for authoritative information on US patent 9980944, including USPTO records and any 2026 CAFC docket activity.

Summary of US Patent 9980944 (US 9,980,944 B2)

Note on scope: The authoritative source I worked from is the full text of US9980944B2 as published on Google Patents (source: https://patents.google.com/patent/US9980944/en). That text is complete through the description but is cut off before the verbatim claim listing, so my claim descriptions below are reconstructed from the patent's own "Summary of the Invention" section plus the district-court record that quotes/construes the claim term. I flag this as a limitation below rather than guessing at verbatim language.

Bibliographic data

Inventors (9): Christoph Max Krell; Marian Misun; Daniel Andreas Niederer; Werner Heinz Pachinger; Marie-Christine Wolf; Daniel Zimmermann; Weidong Liu; Peter J. Stengel; Paul Nichols. Assignment records show the Novartis Pharma AG inventors (Krell, Misun, Niederer, Pachinger, Wolf, Zimmermann) and Array inventors (Stengel, Liu, Nichols) assigned to their respective employers, with Novartis AG later assigning to Array BioPharma, Inc.

Continuation chain (from the patent's Cross-Reference section): a continuation of US 15/053,441 (filed 2016-02-25) → continuation of US 14/974,655 (filed 2015-12-18) → divisional of US 14/057,498 (filed 2013-10-18), which claims priority to US provisional 61/716,169 (2012-10-19). The § 15/445,393 filing is therefore a later continuation in the same family.

Abstract (as published)

"The present invention relates to processes for preparing 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide, processes for preparing crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide, and intermediates useful therefore. Also provided herein are pharmaceutical compositions comprising this crystallized compound."

The compound is binimetinib (CAS 606143-89-9), the active ingredient in MEKTOVI® (Array/Pfizer). The patent's own text notes binimetinib is "a known potent and selective inhibitor of the MEK1 and MEK2 proteins," and that the compound itself was previously disclosed in PCT Pub. No. WO 03/077914 (Example 18), which the patent characterizes as disadvantageous for commercial production.

Plain-language overview of the independent claims

Based on the Summary section and the claim terms construed in litigation, the patent's independent claims fall into five functional groups:

1. Process for making Compound A (binimetinib) — multi-step synthesis

• Step (a): react a compound of Formula (I) (the methyl ester, i.e., 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid methyl ester) with a suitable base (e.g., potassium trimethylsilanolate or sodium hydroxide) to form an intermediate.
• Step (b): react that intermediate with a compound of Formula (II) (an O-protected hydroxylamine, e.g., O-(2-tert-butoxyethyl)hydroxylamine) to give a compound of Formula (III) or a hydrate thereof.
• Step (c): dissolve the Formula (III) compound (or hydrate) in a suitable solvent/solvent system.
• Step (d): deprotect with a suitable deprotecting reagent to yield Compound A (binimetinib).
• P¹ is a protecting group (preferably t-butyl; acid-labile protecting groups generally).

2. Process for making the Formula (III) intermediate — the same steps (a) and (b), claimed for producing the protected amide intermediate (or its hydrate) rather than the final drug. The patent describes two variants: a "one-pot" synthesis in which the step-(a) intermediate (potassium salt "Intermediate 1") is not isolated, and a variant in which the intermediate of Formula (V) is isolated (crystallized/collected by filtration, optionally after acidification with HCl) before step (b).

3. Process for preparing a crystallized form of Compound A — the "crystallized binimetinib" process. Two independent variants are described:

• (a) dissolve Compound A in a solution of (i) a solvent system comprising an ether (e.g., THF) and optionally an alcohol (e.g., methanol), plus (ii) water;
• (b) add a seed crystal suspension to form a suspension mixture;
• one variant adds water directly to the suspension mixture (step "d"); the other first cools the suspension mixture and then adds water (step "c");
• final step: cool the treated mixture to crystallize Compound A.
• The patent describes gradual water addition over 5–35 hours, a final alcohol/ether/water ratio between 40/40/20 and 15/15/70 w/w (preferably ~20/20/60), and cooling to ~1–10 °C. The patent claims a surprising effect: water, normally an anti-solvent (solubility < 0.01%), acts as a co-solvent in this ether/alcohol/water mixture and improves purity and morphology (reduced agglomeration/"stickiness," improved flowability), as illustrated in FIGS. 1–2.

4. Crystallized Compound A prepared by the disclosed process — a product-by-process claim covering crystallized binimetinib, with or without a subsequent milling step (jet-milling or pin-milling).

5. Intermediate compounds — compounds of Formula (I), Formula (V), and Formula (IV) (or a hydrate, preferably the monohydrate), each claimed as useful intermediates for synthesizing Compound A.

6. Pharmaceutical composition — a composition comprising crystallized Compound A, at least one sugar, and at least one cellulose-derivative excipient. The patent describes:

• about 5–35% crystallized Compound A (preferably ~5–11%; e.g., ~6.25% or ~10%);
• about 30–70% sugar (preferably lactose monohydrate at ~55–56%);
• about 20–40% cellulose-derivative excipient (preferably microcrystalline cellulose at ~30–36%);
• optionally croscarmellose sodium (~2%), magnesium stearate (~0.75%), and colloidal silicon dioxide (~0.25%);
• unit doses of ~15 mg or ~45 mg Compound A; prepared by direct compression, as an optionally coated tablet.

7. Method-of-treatment / use claims — treating a proliferative disease (particularly cancer) in a subject by administering a pharmaceutical composition comprising crystallized Compound A with at least one sugar and at least one cellulose-derivative excipient; plus corresponding "use in the preparation of a medicament" and "for use in treatment" claims. Cancers recited include melanoma, pancreatic, ovarian, fallopian tube, peritoneal, biliary, colon/rectal, lung, breast, and others; combination with paclitaxel or everolimus is contemplated.

Litigation and 2026 docket activity

District court (D. Del.): The patent is one of the three "Crystallized Binimetinib Patents" (US 9,562,016; US 9,598,376; US 9,980,944) asserted by Array in Hatch-Waxman ANDA litigation:

• Array BioPharma Inc. v. Alembic Pharmaceuticals Limited, No. 1:22-cv-01277 (D. Del., filed 2022-09-28);
• Array BioPharma Inc. v. Sandoz Inc., No. 1:22-cv-01316 (D. Del., filed 2022-10-06);
• Array BioPharma Inc. v. Teva Pharmaceuticals, Inc., No. 1:23-cv-00625 (D. Del., filed 2023).

On April 16, 2024, Judge Gregory B. Williams construed the disputed term "crystallized [binimetinib]" as "binimetinib in a crystalline form resulting from the use of a solvent mixture of ether and optionally an alcohol," and held the term not indefinite (D.I. 93, 94 in No. 1:22-cv-01277). Under that construction, Array stipulated to non-infringement of the '944 patent (and the '016 and '376 patents) in the Alembic/Sandoz litigation and conceded Teva's non-infringement as well. The Teva case was the subject of a stay dispute in which Array sought to preserve a Federal Circuit appeal of the construction.

Federal Circuit (2026): I found no CAFC docket or decision in 2026 that specifically names US 9,980,944. My searches of 2026 Federal Circuit activity surfaced only unrelated decisions (e.g., Global Tubing LLC v. Tenaris Coiled Tubes LLC (2023-1882, 2023-1883, Feb. 26, 2026); Magnolia Medical Technologies v. Kurin (2024-2001, Mar. 6, 2026); Exafer Ltd. v. Microsoft (2024-2296, Mar. 6, 2026)). The district-court record shows that a CAFC appeal of the "crystallized binimetinib" construction was contemplated by the parties (and that an appeal was expected to take roughly 15 months once filed), but I cannot confirm that such an appeal has yet been docketed or decided, nor can I supply an appeal docket number. This is an explicit uncertainty — I do not have authoritative confirmation of a 2026 CAFC appeal involving this patent.

I also did not retrieve the verbatim text of the issued claims (the supplied full text ends mid-description), so the claim overview above is based on the patent's Summary section and the litigation record rather than a verbatim claim listing; exact claim numbering/dependency could not be independently verified.

Commercial context

• Orange Book: listed against MEKTOVI® (binimetinib 15 mg tablets, NDA 210498), patent use code U-2334, expiration October 18, 2033 (confirmed in FDA ANDA correspondence and the Orange Book-derived listings).
• FDA tentative-approval letters for generic binimetinib ANDAs (e.g., Alembic's ANDA 217678) list the '944 patent with an October 18, 2033 expiration and note Paragraph IV certifications to it.
• Array BioPharma was acquired by Pfizer in 2019; the '944 patent's litigation history is tied to the Pfizer/Array MEKTOVI franchise.

I'll research litigation involving US patent 9980944. Let me start with several targeted searches.

Good — I have some leads. Let me dig into the specific Delaware case numbers.

I have strong details. Let me verify case outcomes and check for any additional cases involving the '944 patent.

Litigation involving U.S. Patent No. 9,980,944

Bottom line: Yes — litigation is known. US 9,980,944 ("Preparation of and formulation comprising a MEK inhibitor," Array BioPharma, Inc.) is one of the three "Crystallized Binimetinib Patents" (with US 9,562,016 and US 9,598,376) that Array has asserted in Hatch‑Waxman ANDA litigation over its MEKTOVI® (binimetinib) product. I identified three district‑court cases in which the '944 patent was a patent‑in‑suit, all in the U.S. District Court for the District of Delaware before Judge Gregory B. Williams. These three case numbers match the litigation entries listed on the patent's Google Patents family page.

Note on sourcing: The Google Patents page itself lists three "US case filed in Delaware District Court" entries with these exact docket numbers (1:23-cv-00625, 1:22-cv-01316, 1:22-cv-01277). The details below are corroborated by PACER/CourtListener dockets, the parties' filed documents, and DrugPatentWatch litigation records. I did not independently retrieve the raw PACER docket for every entry, so docket‑level specifics should be verified against PACER.

1. Array BioPharma, Inc. v. Sandoz Inc.

2. Array BioPharma, Inc. v. Alembic Pharmaceuticals Limited (and Alembic Pharmaceuticals, Inc.)

3. Array BioPharma Inc. v. Teva Pharmaceuticals, Inc.

Important caveats

• No merits adjudication on the '944 patent. Across all three cases, the '944 patent was resolved by settlement/stipulated dismissal. There is no court finding of infringement, validity, or enforceability of the '944 patent that I located.
• The dispositive issue was claim construction, not the '944 patent's merits per se. In the Alembic/Sandoz litigation the court construed "crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethoxy)-amide" ("crystallized [binimetinib]") in a way under which the generics were found non‑infringing; Array said it intended to seek reconsideration and, failing that, to appeal that construction. I did not confirm that a Federal Circuit appeal was actually filed or its outcome — treat any appeal as unverified.
• Possible additional/future cases. Because the '944 patent is Orange‑Book‑listed for MEKTOVI® (expiration listed as Oct. 18, 2033, use code U‑2334), it could be asserted in other or later ANDA suits against additional generics. My search was not exhaustive; I cannot rule out additional cases (e.g., other filers) that did not surface.
• "Outcome" for settled cases reflects the public dismissal terms (settlements are confidential), so specific license/entry terms are unknown.

Suggested verification sources: PACER for D. Del. dockets 1:22-cv-01277-GBW, 1:22-cv-01316-GBW, and 1:23-cv-00625-GBW; CourtListener/RECAP for those dockets; and the Federal Circuit docket/opinions database to confirm whether any appeal of the "crystallized binimetinib" construction was filed.

I'll start by verifying the structured data against live sources for any PTAB proceedings on US 9,980,944.

Let me run a few more targeted searches to confirm whether any petitions exist.

Let me do a final confirmation check against PTAB-specific databases.

PTAB / AIA Trial Analysis — US 9,980,944 ("Preparation of and formulation comprising a MEK inhibitor")

Verification note: I ran multiple live searches (Google Patents family/litigation data, DrugPatentWatch, CourtListener, ANDA bulletins, PTAB decision digests). No IPR, PGR, or CBM proceeding naming US 9,980,944 as the challenged patent surfaced. This is consistent with the structured "PTAB proceedings on file" block, which reports no AIA trial proceedings on file from the USPTO Open Data Portal. I could not independently page through PTAB E2E / PTAB Center for this patent number in this session, so I flag the residual uncertainty — but every independent source I could reach agrees with the ODP's "zero" result, and I found no proceeding number to report. I am not inventing any.

Proceedings overview

Total AIA trial proceedings on US 9,980,944: 0 — no IPRs, no PGRs, no CBMs on file (0 active / 0 claims invalidated / 0 claims sustained / 0 settled / 0 institution-denied). The bottom-line defensive posture is therefore not "the patent is hardened by surviving IPRs" and not "the claims are dead" — it is: all claims of the '944 patent remain live and un-adjudicated at the PTAB, and the entire invalidity fight over this patent family has been fought (and largely won by the generics) in the District of Delaware instead. A defendant today faces a fully intact, untested-at-the-PTAB patent whose real risk profile is defined by district-court claim construction, not by any Board outcome.

(No per-proceeding entries — there are no proceedings to detail. Because PTAB outcomes are the organizing principle of this report and there are none, I substitute the actual adversarial record on this patent below so the report is not an empty shell.)

District-court substitute — Array BioPharma / Pfizer v. generics (no AIA counterpart)

• Forums / dockets: D. Del. 1:22-cv-01277 (Alembic); D. Del. 1:22-cv-01316 (Sandoz); D. Del. 1:23-cv-00625 (Teva) — all before Judge Gregory B. Williams.
• Filed: 2022-09-28 (Alembic); 2022-10-06 (Sandoz); 2023-06-08 (Teva).
• Patent at issue: US 9,980,944, asserted claim 1 (method of treating melanoma using crystallized binimetinib); asserted alongside US 9,562,016 and US 9,598,376 (the "Crystallized Binimetinib Patents," all expiring 2033-10-18).
• Key event — claim construction (2024-04-16): In the Alembic/Sandoz action, the court construed the term "crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide" (i.e., "crystallized [binimetinib]"). Array conceded in the related Teva case that "under the Court's claim construction in the Alembic/Sandoz litigation," Teva does not infringe the Crystallized Binimetinib Patents. That is effectively a non-infringement outcome for the ANDA filers on the crystallized-form claims. (Array disputes the construction is preclusive as to Teva and sought reconsideration; the court's 2024-10-22 order in Teva set a 2024-11-08 deadline for stay motions, and Array opposed Teva's stay motion on 2024-11-22.)
• Settlement: Sandoz settled; the case terminated 2025-01-09 with all claims/counterclaims dismissed without prejudice, each side bearing its own costs, and no adjudication on the merits. Terms of the underlying license/entry agreement are confidential. (Per Robbins Kaplan's ANDA settlement chart: "Nothing prohibits Sandoz from maintaining its existing Paragraph IV certifications... or prohibits FDA from granting final approval to Sandoz's ANDA.")
• Appeal: Not to the Federal Circuit from a PTAB case (there is none). Array signaled it may appeal the district court's claim construction after final judgment in Alembic/Sandoz so the Federal Circuit can review the "crystallized [binimetinib]" term. Whether that appeal has been filed/perfected is beyond what I could confirm in this session — treat as unverified.
• Defensive value: For a defendant today, the operative lesson is that this patent will be fought on claim construction of "crystallized [binimetinib]" (a term the Delaware court read narrowly enough to defeat infringement) and on paragraph IV invalidity in district court — not at the PTAB. There is no Board ruling to cite either for or against validity.

(Litigation source: Array BioPharma Inc. v. Teva Pharmaceuticals, Inc., No. 1:23-cv-00625-GBW, D.I. 15 (joint scheduling letter) and D.I. 19 (Array's opposition to Teva's stay motion) via CourtListener, https://www.courtlistener.com/docket/67486186/array-biopharma-inc-v-teva-pharmaceuticals-inc/; Array v. Alembic complaint via CourtListener, https://www.courtlistener.com/docket/65382822/array-biopharma-inc-v-alembic-pharmaceuticals-limited/.)

Strategic summary

Claim status: UNTESTED at the PTAB; narrowed only by district-court construction. Because there are zero AIA proceedings, no claim of US 9,980,944 has been canceled, held unpatentable, or confirmed patentable by the Board. Claim 1 (method of treating cancer/melanoma with crystallized binimetinib) and all dependent claims remain presumptively valid. The only narrowing on record is the Delaware claim construction of "crystallized [binimetinib]," which functionally knocked out the generics' infringement on the crystallized-form family in the Alembic/Sandoz and Teva actions — but a claim construction is not a validity holding, and it was embedded in a settlement-driven dismissal (Sandoz) rather than a final judgment (as of the records I could verify). Do not tell a client "claims 1–5 are canceled" — that would be false for this patent.

Estoppel landscape: essentially wide open. Since there is no IPR/PGR, § 315(e)(2) estoppel has not attached to anyone on this patent. No petitioner is barred from raising any § 102/§ 103 ground in a future IPR, and no defendant is estopped in district court based on prior Board activity. This cuts both ways: a challenger retains the full universe of prior-art grounds, and Array retains the full patent with no adverse PTAB record. The practical estoppel risk here is litigation estoppel from the Delaware cases (e.g., issue preclusion from the Alembic/Sandoz claim construction if and when reduced to final judgment), not AIA estoppel.

Pattern signals. There is no serial-petition pattern because there are no petitions at all. No defensive aggregator (e.g., Unified Patents) appears in this patent's chain — the adversaries are ANDA filers (Alembic, Sandoz, Teva), each acting in its own commercial interest. The patent owner (Array BioPharma, now under Pfizer) has pursued district-court enforcement, not PTAB appeals — there is no PTAB appeal for it to pursue. The family has a documented litigation history (Google Patents lists three Delaware District Court cases) but no AIA track. Note the timing: the '944 patent issued 2018-05-29 and was asserted starting in 2022; the 2022–2023 filing window preceded the 2025 tightening of PTAB institution practice, and the generics nonetheless chose the district court (paragraph IV) path rather than IPRs — likely because an ANDA case already forces the validity/construction issues into a single forum with the 30-month stay machinery.

Recommended next steps

• If you are a defendant being asserted against today: You are facing a patent with no PTAB record in either direction and therefore no § 315(e)(2) estoppel and no helpful FWD to cite. Plan the defense around (a) the Delaware "crystallized [binimetinib]" construction — press the same construction in your case and note Array's own concession in the Teva action that, under that construction, the ANDA product does not infringe the crystallized-form patents; and (b) a fresh § 102/§ 103 invalidity theory, which is fully available because no ground has been raised or could have been raised in a Board proceeding (none exists).
• If you are considering filing an IPR: There is no statutory bar or estoppel and no duplicative-proceeding problem on this patent yet, but weigh the current institution climate — the Board's 2025–2026 discretionary-denial practice ("settled expectations," parallel-litigation stipulations such as Sotera-style requirements) makes institution harder for patents already in litigation. See the Board's recent informative decisions and Director-review trends (USPTO PTAB Decisions, https://www.uspto.gov/patents/ptab/decisions). If you file, expect the panel to scrutinize any parallel district-court invalidity contentions under the stipulation case law.
• No active PTAB milestones to track. There is no institution deadline, no oral hearing, and no statutory FWD due date, because no trial was instituted. Monitor the Federal Circuit instead for any appeal of the "crystallized [binimetinib]" claim construction out of the Alembic/Sandoz (and, if pursued, Teva) district-court judgments; that appellate ruling — not the PTAB — will be the event that reshapes this patent's enforceability.
• The absence of PTAB activity is itself the signal. Well-asserted Orange Book patents frequently attract IPRs; the fact that this one drew three ANDA suits but zero petitions suggests challengers concluded the district court (and claim construction) was the better battleground. Verify the "zero proceedings" result directly at PTAB Center / E2E (https://ptacts.uspto.gov/) before relying on it in a filing, and re-run the check periodically, since a petition could have been filed and not yet indexed in the sources I could reach.

Caveats I will not paper over: (1) I found no proceeding number, petitioner, panel, FWD, or settlement for any PTAB case on this patent and have not manufactured any. (2) The Sandoz settlement terms and any Teva/Alembic resolution terms I did not see are confidential or unverified. (3) The district-court facts above are drawn from pleadings and orders surfaced in search, not from a complete docket review; confirm against PACER/CourtListener before relying on them.

I'll research the assignment record for US 9,980,944 across USPTO records and the corporate/legal context.

Let me search for the specific reel/frame numbers and the Novartis-Array agreements.

I hit my search-tool step limit before I could pull the raw Assignment Center entries (reel/frame and correspondent). Below I have reconstructed the chain from the USPTO-derived assignment events shown in the patent's own record on Google Patents, plus corporate/securities context. I flag explicitly where reel/frame and correspondent data are missing rather than fabricating them.

Inventors

Nine named inventors, split cleanly into two employer groups — a two-company joint invention:

Pattern note: This is not an "inventors departing the original assignee" scenario. The 6/3 Novartis:Array inventorship split is the classic signature of a co-development / co-ownership arrangement — six Novartis chemists who developed the crystallization process and three Array inventors who owned the underlying compound and the original synthesis (see prior section: Compound A was first disclosed in WO 03/077914, Array's own filing). The dual-employment inventorship is what drove the multi-step assignment chain below: each set of inventors assigned to their own employer first, then the two corporate owners had to consolidate title.

Original assignee

Array BioPharma, Inc. (Delaware corporation; principal place of business 3200 Walnut Street, Boulder, CO 80301) is the original assignee named on the issued patent.

• Primary line of business: commercial-stage biopharmaceutical company discovering and developing targeted small-molecule oncology drugs.
• Product embodying the claims: YES — MEKTOVI® (binimetinib), 15 mg tablets, NDA 210498, FDA-approved 2018-06-27. The '944 patent claims a process for preparing crystallized binimetinib and is Orange Book-listed against MEKTOVI with patent use code U-2334, expiration 2033-10-18. (Confirmed in FDA ANDA correspondence for Alembic's ANDA 217678.)
• Current status: Acquired. Pfizer Inc. acquired Array BioPharma for $11.4 billion ($48/share cash), announced 2019-06-17 and closed in the second half of 2019. Array BioPharma, Inc. continues to exist as a Pfizer subsidiary (which is why the patent's recorded assignee of record still reads "Array BioPharma, Inc." and why no separate Pfizer merger conveyance appears for this patent — see signals below). Not dissolved, not in bankruptcy.

Legal-note flag (inherited and still true): the U.S. litigation and FDA records still name "Array BioPharma, Inc." as the NDA holder and Orange Book listee; the real party in interest behind the '944 assertion has been Pfizer/Array since 2019.

Assignment timeline

Data-availability caveat (read first): The Assignment Center / assignment.uspto.gov records for US 15/445,393 exist (the events below are drawn from the patent's USPTO assignment-event feed), but I was not able to retrieve the reel/frame numbers or the recorded correspondent (attorney/firm) within my search budget. I have therefore left those fields marked [NOT RETRIEVED] rather than guess. Everything else (conveyance type, assignor, assignee, execution/recording dates) is as recorded.

• 2017-03-15 (recorded 2017-03-15) — Reel/Frame [NOT RETRIEVED]

  • Conveyance: Assignment
  • Assignor: Peter J. Stengel; Weidong Liu; Paul Nichols
  • Assignee: Array BioPharma, Inc.
  • Correspondent: [NOT RETRIEVED]
  • Context: Inventor-to-employer assignment — the three Array inventors conveying their rights to Array. Routine; establishes Array's half of co-ownership.

• 2017-03-15 (recorded 2017-03-15) — Reel/Frame [NOT RETRIEVED]

  • Conveyance: Assignment
  • Assignor: Christoph Max Krell; Marian Misun; Daniel Andreas Niederer; Werner Heinz Pachinger; Marie-Christine Wolf; Daniel Zimmermann
  • Assignee: Novartis Pharma AG
  • Correspondent: [NOT RETRIEVED]
  • Context: Inventor-to-employer assignment — the six Novartis inventors conveying their rights to Novartis Pharma AG.

• 2017-03-15 (recorded 2017-03-15) — Reel/Frame [NOT RETRIEVED]

  • Conveyance: Assignment
  • Assignor: Novartis Pharma AG
  • Assignee: Novartis AG
  • Correspondent: [NOT RETRIEVED]
  • Context: Internal corporate reorg — Novartis Pharma AG (the operational Basel entity that employed the inventors) conveying up to the Novartis AG parent. Not a sale; no third party.

• 2017-05-18 (recorded 2017-05-18) — Reel/Frame [NOT RETRIEVED]

  • Conveyance: Assignment
  • Assignor: Novartis AG
  • Assignee: Array BioPharma, Inc.
  • Correspondent: [NOT RETRIEVED]
  • Context: Consolidation of title / rights transfer to the originator. This is the tail end of the 2015 "Novartis Agreements," under which Novartis handed global rights to encorafenib (LGX818) and binimetinib (MEK162) back to Array; Array's own investor filing states the Novartis Agreements transferred "global ownership of both assets" to Array (Array 10-K/AR disclosure, reflecting $85.0M upfront from Novartis and a low-single-digit royalty back to Novartis). The recordation simply completed the paper title so Array held 100% of the '944 invention.

No records found for any post-2018 assignment, including a Pfizer/Array merger conveyance. If the Assignment Center confirms that, it is itself the key finding: the chain terminates at an operating company and has never been transferred to a licensing entity.

Timeline diagram

timeline
    title Ownership of US 9980944
    2012 : Priority filing 61/716169
    2013 : Parent app 14/057498 filed
    2015 : Novartis returns global rights to Array
    2016 : Continuation 15/053441 filed
    2017 : App 15/445393 filed Feb
         : Array inventors assign to Array Mar 15
         : Novartis inventors assign to Novartis Pharma Mar 15
         : Novartis Pharma assigns to Novartis AG Mar 15
         : Novartis AG assigns to Array May 18
    2018 : Patent issues May 29
         : MEKTOVI approved Jun 27
    2019 : Pfizer acquires Array for 11.4B
    2022 : Array sues Alembic and Sandoz
    2023 : Array sues Teva

NPE / troll-pattern signals

1. Shell-entity transfer — Not present. Every recorded assignee is a named operating entity: Array BioPharma, Inc. (NDA holder for MEKTOVI), Novartis Pharma AG and Novartis AG (both Basel operating/parent entities). No "IP / Holdings / Ventures / Licensing" suffix, no registered-agent address, no single-purpose LLC anywhere in the chain. Assignee address of record is Array's Boulder, CO campus (3200 Walnut Street), not a service address.

2. Known asserter in the chain — Not present. No assignee matches Acacia, Marathon, Intellectual Ventures, IPNav, Wi-LAN, Conversant/Mosaid, Vringo, Pendrell, Round Rock, Spangenberg entities, or any Unified/RPX high-frequency-plaintiff list. The plaintiffs of record (Array BioPharma, Inc. v. Alembic / Sandoz / Teva) are the brand NDA holder suing generic ANDA filers — the opposite of the NPE model.

3. Repeat correspondent across the chain — Unclear (data gap). This is the one signal I could not evaluate: I did not retrieve the recorded correspondent attorney/firm for any of the four 2017 entries. Given that three of the four recordings occur on a single day (2017-03-15) and the fourth six weeks later (2017-05-18), a single law firm very likely handled all four — but that is an inference, not a finding. Verify at the Assignment Center before relying on it.

4. Cascading transfers — Not present. Though there are four assignments, three are simultaneous same-day conveyances needed to consolidate co-ownership, and the fourth is the Novartis→Array rights return. There is no chain of successive LLC-to-LLC hops; the chain converges on Array rather than bouncing through intermediaries.

5. Pre-litigation transfer — Not present. The last assignment (2017-05-18) predates the first '944 infringement suits (2022-09-28 Alembic; 2022-10-06 Sandoz) by more than five years. No assignment sits in the 6-month pre-suit window.

6. Bankruptcy fire-sale — Not present. No assignor or assignee has a Chapter 7/11 event in this chain; Array was acquired at a premium ($48/share, 62% premium), not liquidated.

7. Privateering — Not present. The direction of transfer runs toward the operating originator (Novartis→Array), not from an operating company out to an NPE. There is no evidence of an NPE asserting on Array's/Pfizer's behalf; Array asserted in its own name as NDA holder.

8. Defensive aggregator (anti-NPE) — Not present. The chain does not terminate at RPX, AST, LOT, Unified, or OIN.

Verdict

Operating-company assertion.

Array BioPharma, Inc. — the original assignee and the holder of NDA 210498 for MEKTOVI (binimetinib) — is the asserting party, and its complaint in Array BioPharma Inc. v. Teva Pharmaceuticals, Inc. (D. Del. 1:23-cv-00625) expressly pleads that Array holds the approved NDA and that MEKTOVI is Orange-Book-listed. The only assignments in the record are the 2017-03-15 inventor-to-employer conveyances (Array inventors → Array; Novartis inventors → Novartis Pharma AG; Novartis Pharma AG → Novartis AG) and the 2017-05-18 Novartis AG → Array consolidation that closed out the 2015 Novartis rights return — i.e., a joint-ownership cleanup, not a transfer to an asserter. No post-2018 assignment (including any Pfizer merger conveyance) appears, and no shell entity, known NPE, or defensive aggregator appears anywhere in the chain. The operating company that ships the product embodying the claims is suing actual generic competitors.

Verification links:

• USPTO Assignment Center (search by patent 9980944 or app 15/445,393): https://assignmentcenter.uspto.gov/
• Legacy assignment search: https://assignment.uspto.gov/patent/index.html

Two open verification items I could not close: (a) the reel/frame numbers for all four 2017 recordings, and (b) the recorded correspondent for each — both should be read directly off the Assignment Center entries. Neither gap changes the NPE analysis, because the identity of the assignees is not in dispute.

I'll research the prior-art citations for US 9,980,944 specifically. Let me run targeted searches.

Let me look for the specific front-page "References Cited" list on the patent.

Let me try to retrieve the actual front-page citations from alternate patent databases.

Prior-Art Analysis — US 9,980,944 B2

Scope, sourcing, and an important caveat up front

Patent identity confirmed (matches the number literally, no auto-correction): US 9,980,944 B2, application US 15/445,393, filed 2017-02-28, granted 2018-05-29, titled "Preparation of and formulation comprising a MEK inhibitor," Array BioPharma Inc. / Novartis Pharma AG, earliest priority 2012-10-19 (prov. 61/716,169). This is the same document used in the earlier sections, so I will not repeat its bibliographic or litigation content.

Critical sourcing caveat you should weigh: I was not able to pull the verbatim front-page "References Cited" block of US 9,980,944 itself. The Google Patents page for '944 (the authoritative source used throughout this analysis) returns the description and the "Info" block, but my searches did not surface its References-Cited table, and I do not have direct PatentCenter/Patent Full-Text (patft) access through my tools — only general web search. What I did retrieve is the citation list that PubMed/ PubChem aggregates for the sibling family member US 10,729,678 B2 ("Preparation of and formulation comprising a MEK inhibitor," same specification family, granted 2020-08-04). Because the '944 and '078 share one specification and one priority date, their cited-art lists are expected to overlap heavily — but I cannot guarantee they are identical. Treat the lists below as the family's cited-art landscape, not as a certified reproduction of the '944's own front page.

Second caveat: as noted in my earlier sections, the supplied full text of '944 ends mid-description, so I do not have the verbatim claim set. Anticipation mapping below is therefore done against the claim groups identified earlier (process claims; intermediate-compound claims; crystallization-process claims; product-by-process/"crystallized Compound A" claims; formulation claims; method-of-treatment/use claims), not against verified claim numbers.

Third caveat: "anticipates under § 102" is a legal conclusion. Everything below is a potentially anticipates screening, as you requested, not a validity opinion.

Part 1 — Patent citations associated with the '944 family

Part 2 — Non-patent literature citations associated with the family

Part 3 — Bottom-line anticipation screen by claim group

1. Process claims (steps a–d) and the Formula (III) intermediate-process claims. The only serious § 102 candidate is WO 03/077914 Example 18 (and its U.S. sibling US 7,235,537). Anticipation turns entirely on whether Example 18 discloses the same base/activation/coupling/deprotection sequence with the same P¹-protected hydroxylamine. The '944 specification itself frames WO 03/077914's Example 18 as "although suitable, regarded as disadvantageous for commercial production," which is an implicit admission that the reference discloses a process for Compound A — supporting a § 102 or at minimum a strong § 103 attack on the broad process claims, but not necessarily on every recited limitation.
2. Intermediate-compound claims (Formulae I, V, IV). This is where § 102 exposure is highest: the methyl ester (Formula I / "Compound 3"), the carboxylic-acid/salt intermediates (Compound 6 / Formula (V)/(IV)), and O-(2-tert-butoxyethyl)hydroxylamine (Compound 4, CAS 1023742-13-3, a commercial reagent) are all either disclosed in the WO 03/077914 family or commercially available. Expect WO 03/077914 / US 7,235,537 to be cited here.
3. Crystallization-process claims. Not anticipated by anything in the list; WO 03/077914 does not teach crystallization from a THF/methanol/water system with staged water addition. Exposure here is § 103 (Caira + routine optimization), which is exactly the ground the Novartis side would argue is overcome by the claimed "water as co-solvent" surprise (solubility improvement ~50%, FIGS. 1–2 morphology).
4. Product-by-process "crystallized Compound A" claims. Under the D. Del. construction ("…crystalline form resulting from the use of a solvent mixture of ether and optionally an alcohol"), the process limitation is imported into the claim; WO 03/077914 (2003) does not use that solvent mixture, so it should not anticipate under that construction. Note the tension flagged earlier: that same construction is what led to the stipulations of non-infringement, and it cuts in favor of patentability over WO 03/077914 as much as it cut against infringement.
5. Formulation claims (Compound A + sugar + cellulose derivative). No listed reference anticipates. WO 03/077914 discloses the compound, not the lactose-monohydrate/MCC/croscarmellose/magnesium-stearate/silica tablet. Exposure is § 103 over the compound + standard excipient formularies (e.g., Remington's), which the '944 already cites in its own specification.
6. Method-of-treatment / use claims. N12/N13 (Finn 2012; Ascierto 2012) are the closest § 102-adjacent references, but neither discloses the claimed crystallized-compound-plus-sugar-plus-cellulose composition, so they support § 103 substantially more than § 102.

Part 4 — What I could not verify, and what I recommend

• I could not retrieve the '944 patent's own front-page "References Cited" list. The list above comes from the PubChem citation set for sibling US 10,729,678 B2. If you need court-ready accuracy, pull the '944 front page directly (PatentCenter for US 15/445,393, or the patent PDF at patentimages storage).
• Publication dates I did not independently confirm: WO 00/42022 (assumed 2000-07-20), WO 2007/002092 and WO 2007/002157 (assumed 2007-01-04), WO 2009/064675 (assumed 2009-05-22), WO 2010/121646 (assumed 2010-10-28), US 9,156,795 (2015-10-13), US 9,382,212 (2016-07-05). Treat these as provisional.
• Content not verified for references 1, 3, 4, 6, 7, 8, 12, and N4. I deliberately did not invent subject matter for these. Before using any of them in an invalidity chart, retrieve the documents themselves.
• Highest-value next retrieval: the ISR and IPRP for PCT/US2013/065633 (items N5–N6). The ISR is the examiner's own prior-art citation list for this family and will tell you exactly which references were treated as anticipatory vs. obviousness-type art — this is the most reliable substitute for the front-page References-Cited block I could not reach.
• No contradiction with the earlier sections was found: the WO 03/077914 "disadvantageous for commercial production" statement, the priority chain, and the "crystallized binimetinib" claim construction all align with the prior-art picture above. The only item worth flagging is the tension between the D. Del. construction and product-by-process § 102 doctrine noted in Part 3(4) — the imported process limitation both defeats infringement and blunts any WO 03/077914 anticipation argument against the crystallized-product claim.

I'll ground this analysis in the prior-art record for this patent. Let me verify the key references and any obviousness rulings on this family.

Let me pin down the reference list cited on the face of this patent and the generic's obviousness contentions.

Obviousness Analysis — U.S. Patent No. 9,980,944 ("Preparation of and formulation comprising a MEK inhibitor")

Analysis date: April 26, 2026 · Statutory basis: 35 U.S.C. § 103 (Graham v. John Deere; KSR Int'l v. Teleflex)

0. Scope, sources, and a flagged contradiction

What I was able to verify and what I could not. The authoritative text available to me is the Google Patents full text of US 9,980,944 (https://patents.google.com/patent/US9980944/en). As noted in the previously generated "Patent summary," that text ends mid-description and does not include the verbatim issued claim listing. The Google Patents page in the supplied material contains a "Prior art keywords" field and an inline list of the patent's own described compounds, but not a structured "Patent Citations / References Cited" block. I therefore ground the reference set below on (a) references the specification itself names (principally WO 03/077914), (b) the patent family/Orange Book record, and (c) the district-court record, and I flag each item's provenance.

⚠️ Contradiction to flag explicitly. The previously generated "Patent summary" reconstructed the claim set from the patent's Summary of the Invention section — i.e., process claims, crystallized-compound product-by-process claims, intermediate claims, composition claims, and method-of-use claims. The litigation record says otherwise for the '944 patent specifically: it reports claim 1 as a method of treating BRAF-mutant melanoma by administering a composition comprising crystallized binimetinib, and refers to "claims 1–12 of the '944 patent." See Ex Parte complaint analysis, Array BioPharma Inc. v. Teva Pharmaceuticals, Inc., No. 1:23-cv-00625-GBW ("claims methods of treating specific types of melanoma, namely BRAF-mutant melanoma … (’944 Patent, Abstract; claim 1)"), https://ai-lab.exparte.com/case/dct/ded/1:23-cv-00625/doc/analysis/1; and the Alembic stipulation listing "claims 1-12 of the '944 patent," https://storage.courtlistener.com/recap/gov.uscourts.ded.80177/gov.uscourts.ded.80177.131.0.pdf.

These two accounts cannot both be complete. Because the instruction is to interpret the record literally and prefer verified search results, I treat the litigation-reported claim 1 (BRAF-mutant melanoma method) as the operative independent claim, and I separately analyze the other claim categories that the '016/'376 siblings and the '944 specification describe, since the family shares a single specification. I do not have verbatim claim text and will not fabricate claim numbering. Treat §4.A as highest-confidence and §4.B–F as category-level analysis.

1. Framework and the person of ordinary skill

Under Graham the analysis turns on (1) the scope/content of the prior art, (2) the differences between the prior art and the claims, (3) the level of ordinary skill, and (4) objective indicia. Under KSR, "if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond his or her skill"; and a combination of familiar elements according to known methods is likely obvious when it "does no more than yield predictable results."

POSA (proposed): a medicinal chemist or pharmaceutical formulation scientist with an advanced degree (Ph.D. or M.S.) plus several years of experience in small-molecule process chemistry and oral solid-dosage development, and working knowledge of standard tablet-excipient selection and of crystallization by cooling/anti-solvent/seeding. This is a modest skill level; the patent itself repeatedly describes its process steps as conventional (e.g., "It is within the knowledge of one of ordinary skill in the art to optimize the process").

Priority / §103 version. The earliest priority date is 2012-10-19 (US provisional 61/716,169), which is before the AIA first-inventor-to-file date (2013-03-16). If the claims are entitled to that priority, pre-AIA § 103(a) governs and the cleanest art is § 102(b) art published more than one year before the critical date. This matters: WO 03/077914 (2003) qualifies under § 102(b); the 2012 clinical abstracts (Ascierto, Finn) do not, and would be § 102(a)/(g) art at best. If any claim limitation (e.g., the specific crystallization protocol or the BRAF-mutant-melanoma indication) is not supported by the 2012 provisional, that claim loses the 2012 priority and the AIA applies, making the 2012–2015 clinical and formulation literature fully available as § 102(a)(1) art. I flag this as a first-order issue to resolve before relying on any combination below.

2. Prior art of record / reference set

Explicitly not prior art: WO 2014/063024 — this is the international publication of the same application family (same 2012-10-19 priority) and is routinely (and wrongly) cited against the '944 patent. It cannot be § 102 art to the '944 patent. Similar caution applies to sibling US 9,562,016 / US 9,598,376.

3. Motivation to combine — the unifying rationale

The '944 specification supplies the motivation in its own words: the WO 03/077914 process "is disadvantageous for commercial production," and there is "a need to provide processes that fulfill one or more of the following criteria: scalable, safer, simpler, higher yielding and more economical." Once a lead compound is in clinical development, the POSA has a strong, articulated motivation to (i) scale the synthesis, (ii) crystallize the API for purity/flow, and (iii) put it into a standard oral tablet for the indication under study. These are the ordinary, predictable tasks of pharmaceutical development.

4. Claim-by-claim obviousness

A. Method of treating BRAF-mutant melanoma with a composition comprising crystallized binimetinib (claim 1 and dependents, per the litigation record) — strongest prima facie case

Combination: [A] + [C] (or [D]) + [E]/[F] (+ [I] for "crystallized").

• [A] discloses binimetinib and expressly teaches that it is a MEK1/2 inhibitor useful for treating hyperproliferative disease, particularly cancer (melanoma among the enumerated cancers in the family).
• [C] reports that binimetinib produces responses in BRAF^V600-mutant melanoma — supplying both the specific cancer limitation and a reasonable expectation of success in humans.
• [E]/[F] teach that a small-molecule API is dosed as an oral tablet containing a diluent such as lactose monohydrate and/or microcrystalline cellulose (plus disintegrant/lubricant/glidant).
• "Crystallized": pharmaceutically acceptable drug substances are routinely prepared as crystalline solids; obtaining a crystalline form of a known API is ordinary practice ([I]). The specification itself frames the crystalline form as a manufacturing convenience, not a new therapeutic entity.

Why the POSA would combine: the compound was already in Phase I/II for melanoma; the only remaining question was how to present it orally. Using the art-recognized excipient set is "the predictable use of prior-art elements according to their established functions," which KSR holds is not patentable. Result: prima facie obvious.

B. Pharmaceutical-composition claims (crystallized binimetinib + at least one sugar + at least one cellulose-derivative excipient; lactose monohydrate ~55–56% + MCC ~30–36%; croscarmellose Na ~2%, Mg stearate ~0.75%, colloidal SiO₂ ~0.25%)

Combination: [A] + [E]/[F] (+ [I]).

Lactose and microcrystalline cellulose are the two most common direct-compression tablet diluents, and croscarmellose sodium, magnesium stearate, and colloidal silicon dioxide are, respectively, a standard disintegrant, lubricant, and glidant. Selecting a sugar diluent (lactose) plus a cellulosic diluent (MCC) is the textbook pairing for balancing compressibility and flowability in a low-dose/high-potency tablet (the API is only ~5–11% w/w). Where the art discloses the active and the conventional carrier, the composition is obvious absent a showing that the specific excipient combination yields an unexpected property attributable to the claimed combination. Prima facie obvious.

C. Process claims for Compound A and the Formula (III) intermediate (saponify methyl ester → couple → deprotect; one-pot vs. isolated Formula (V) variants)

Combination: [A] + [G] + [H].

• [A], Example 18, already discloses making binimetinib via the same late-stage logic from the methyl ester.
• The claimed steps are the canonical textbook sequence: base saponification of the methyl ester ([H]); CDI activation coupling with an O-protected hydroxylamine such as O-(2-tert-butoxyethyl)hydroxylamine ([H]); acid-labile t-butyl deprotection with aqueous acid ([G], and the specification itself lists phosphoric/HCl/sulfuric acid, HCl/IPA, TMSCl, TFA, p-TsOH).
• The "one-pot vs. isolate Formula (V)" choice is a routine process-design/economic decision (telescoping vs. isolating a crystalline salt/acid to purge impurities). The specification even concedes that "it is within the knowledge of one of ordinary skill … to optimize." Choosing the preferred base (KOMe₃Si or NaOH), solvent (DMF/THF), and proton source (imidazole·HCl) is routine optimization of known parameters. Prima facie obvious.

D. Crystallization-process claims (dissolve in ether/alcohol/water → seed → add water over 5–35 h → cool to 1–10 °C; final alcohol/ether/water ratio 40/40/20–15/15/70)

Combination: [A] + [I]. Crystallizing a known API by dissolving it hot, seeding, adding an anti-solvent, and cooling slowly are each standard unit operations ([I]). The claim elements (THF, methanol, water; seeding; controlled cooling) are familiar. A prima facie case can be made, but this is the category where the patent's rebuttal is strongest (see §5) — the asserted, counter-intuitive finding that water acts as a co-solvent in the THF/methanol system (~50% solubility increase) is the one genuinely non-routine technical assertion in the specification. Expect a genuine factual fight over whether that effect (i) exists, (ii) is attributable to the claimed parameters, and (iii) would have been expected.

E. Product-by-process claim: "crystallized binimetinib" prepared by the disclosed process

Combination: [A] + [I]. For a product-by-process claim, patentability is judged on the product itself, not the process. If the crystalline product is a form already obtainable and described/obvious from the prior art (or a routine crystalline form of a known compound), the claim is obvious/anticipated regardless of the new process. Note that the Delaware construction ("binimetinib in a crystalline form resulting from the use of a solvent mixture of ether and optionally an alcohol") narrowed this term so heavily that the generics' products were held non-infringing — which itself signals the difficulty of sustaining broad coverage over the art. Prima facie obvious absent demonstrated unexpected properties of the crystal form per se.

F. Intermediate-compound claims (Formulae (I), (V), (IV) monohydrate)

Combination: [A] + [G]/[H]. Formula (I) (the methyl ester) and its downstream acid/salt are disclosed or rendered obvious by the WO 03/077914 synthetic route; a novel single intermediate in a known multi-step route is obvious where the POSA would have made it "as a matter of obvious design choice" en route to a compound the art already sought to make. If, as the litigation suggests, the '944 patent does not actually contain these claims (they may reside in the siblings), this category is moot for this patent — flagged for verification.

5. Objective indicia (secondary considerations) and the rebuttal posture

The patent asserts, and would argue:

1. Unexpected solvent effect — water, normally an anti-solvent (solubility < 0.01%), increases binimetinib solubility ~50% in THF/methanol/water. This is the strongest non-obviousness argument, but it is tied to the crystallization-process claims (category D), not to the composition or method claims.
2. Improved purity and morphology — reduced agglomeration (vs. prior 15 mm lumps) and improved flowability (FIGS. 1–2). Weak: reduced agglomeration/improved flow are the expected consequences of controlled crystallization and of the standard jet-/pin-milling steps the patent also employs.
3. Commercial success / long-felt need — MEKTOVI® is a commercial product. Nexus problem: the commercial value flows from binimetinib the compound (already disclosed in [A]) and its clinical profile, not from the claimed "crystallized … + lactose + MCC" features. Under settled law, commercial success without a nexus to the claimed advance carries little weight.
4. Copying by generics — expected in ANDA practice and of minimal probative value.

Net: the unexpected-results/rebuttal case is confined largely to the crystallization process and, at most, the specific crystalline form. It does not rescue the method-of-treatment ([A]+[C]), composition ([A]+[E]/[F]), or synthetic-process ([A]+[G]/[H]) claims.

6. Bottom line

• Best combinations for a § 103 challenge:
  • Method-of-treatment claim 1: WO 03/077914 + Ascierto 2012 (BRAF^V600 melanoma) + Remington's/Handbook of Excipients (+ crystallization art for "crystallized").
  • Composition claims: WO 03/077914 + Remington's/Handbook of Excipients (lactose + MCC + conventional disintegrant/lubricant/glidant).
  • Process claims: WO 03/077914 (Example 18) + Greene's Protective Groups + standard saponification/CDI-coupling methodology.
  • Crystallization/product-by-process claims: WO 03/077914 + standard crystallization texts — but the "water-as-co-solvent / improved morphology" unexpected-results evidence is a genuine issue.
• Motivation is not the weak link. The specification itself supplies the motivation ("scalable, safer, simpler, higher yielding, more economical"), and KSR makes predictable, routine combinations of known elements obvious.
• Real-world signal (unverified as to outcome): in Array v. Teva, Teva's Paragraph IV Detailed Statement asserted that "all claims of the '376[] and '944 patents are invalid as obvious" (complaint ¶29, https://paragraphfour.com/wp-content/uploads/2022/09/dedc23cv0625C.pdf). This is a party's contention, not a holding. In the Alembic/Sandoz action, Array stipulated to non-infringement of the '944 claims under the court's construction but did not concede validity. As the earlier sections established, there is no PTAB record and no merits validity ruling on the '944 patent.

7. Caveats I will not paper over

1. I do not have verbatim claim text. The claim categories above derive from the litigation record and the specification; exact numbering, dependency, and whether intermediate/process claims actually issue in the '944 patent (versus the '016/'376) must be confirmed against the USPTO PatentCenter claim listing.
2. The contradiction in §0 is unresolved. The Summary-section-based claim reconstruction and the litigation-reported claim 1 (BRAF-mutant melanoma method) cannot both be right; I have analyzed both rather than assert a synthesis.
3. Priority/AIA status is undetermined and materially affects which 2012–2015 references qualify.
4. No controlling obviousness decision exists for this patent. My combinations are analytical, not adjudicated; any of them could fail on the "unexpected results" or "criticality of process parameters" evidence if the patentee proves the water/solvent effect is real and unexpected.