US 10646550

I'll search for authoritative information on this specific patent number, including any 2026 litigation activity.

Let me search specifically for litigation and PTAB proceedings involving this patent, and verify the claim set.

Let me retrieve the full claim set for this patent.

US Patent 10,646,550 — Analyst Summary

Important scope note: I searched for the literal identifier 10646550 (US 10,646,550 B2). I did not locate any Court of Appeals for the Federal Circuit 2026 docket in which US 10,646,550 itself is the patent on appeal. The 2026 CAFC activity in the BioMarin/vosoritide space that my searches surfaced centers on different patent numbers (RE48,267 and 12,233,106) — details below. I flag this explicitly rather than attributing unrelated litigation to this patent.

Bibliographic data (high confidence)

Per the specification, the application is a divisional of U.S. application Ser. No. 15/225,355, filed Aug. 1, 2016. Google Patents also shows later continuations claiming priority to this patent (e.g., 16/837,910 → US 11,590,204; 16/837,905 → US 11,914,446; 18/157,573 → US 12,076,372; 18/425,954 → US 12,514,906; 18/785,340 → US 2024/0374688 A1).

Abstract (verbatim)

"The present disclosure provides for use of variants of C-type natriuretic peptide (CNP), and novel pharmaceutical compositions and formulations comprising CNP variant peptides for the treatment of skeletal dysplasias, one or more symptoms of skeletal dysplasias, such as long bone growth or growth velocity, and other disorders having a skeletal dysplasia and/or CNP-associated symptom or component."

Independent claim — plain-language overview

The patent has one independent claim (claim 1); claims 2–8 are dependent. (DrugPatentWatch's excerpt renders claims 1–8; I could not confirm the total claim count from an authoritative full-text source — treat the claim count as uncertain.)

Claim 1 is a method of treating skeletal dysplasia and has four required components:

1. The act: administering a composition to a subject (a treatment method claim, not a compound claim).
2. Dose floor: the CNP variant peptide must be administered in an amount of at least 7.5 μg/kg.
3. The active agent (Markush group of seven peptides): CNP-37(M32N) (SEQ ID NO:1); Met-CNP-37 (SEQ ID NO:2); Pro-CNP-37 (SEQ ID NO:3); Gly-CNP-37(M32N) (SEQ ID NO:4); Pro-Gly-CNP-37 (SEQ ID NO:5); Met-Gly-CNP-37 (SEQ ID NO:6); and Gly-CNP-37 / CNP-38 (SEQ ID NO:7). Pro-Gly-CNP-37 is the peptide corresponding to the commercial drug vosoritide.
4. A required formulation: the composition must comprise citric acid monohydrate, sodium citrate dihydrate, trehalose dihydrate, D-mannitol, L-methionine, and polysorbate 80 — i.e., the claim is locked to the specific reconstituted lyophilized buffer/excipient system disclosed (the specification's Example describes the 2.0 mg/mL and 10 mg/mL formulations at pH 5.5).

The claim closes with "wherein the step of administering treats said skeletal dysplasia."

Dependent claims (as excerpted):

• Claim 2 — treatment results in improvement in one or more listed symptoms (increased absolute growth; increased growth velocity; increased QCT BMD; improved growth plate morphology; increased long-bone growth; improved spine morphology; improved elbow range of motion; decreased sleep apnea).
• Claim 3 — the skeletal dysplasia is a member of a long recited list (achondroplasia, hypochondroplasia, thanatophoric dysplasia, osteogenesis imperfecta, achondrogenesis, diastrophic dysplasia, etc.).
• Claim 4 — administration once daily.
• Claim 5 — once daily over a period of at least 6 months.
• Claim 6 — subcutaneous administration.
• Claim 7 — dose of at least about 15 μg/kg per day.
• Claim 8 — further limitation on the formulation (text truncated in the source; likely specifying the formulation pH/concentration parameters, e.g., about 5.5 / about 10 mg/mL — I cannot confirm this precisely).

Litigation / PTAB status (as of the search results retrieved)

• No CAFC 2026 appeal specific to US 10,646,550 was found. Google Patents flags that the family has litigation (Darts-IP family 56682280), which is consistent with the VOXZOGO patent disputes, but I could not tie a 2026 Federal Circuit docket to this patent number.
• 2026 CAFC case in the same commercial dispute is a different patent: Ascendis Pharma A/S v. BioMarin Pharmaceutical Inc., No. 2026-1026 (Fed. Cir. Mar. 26, 2026) (opinion by Stoll) — affirmed denial of a mandatory stay under 28 U.S.C. § 1659(a)(2) in a declaratory-judgment/ITC dispute concerning RE48,267 (ITC Inv. No. 337-TA-1447).
• 2026 ANDA suit is a different patent: BioMarin Pharm. Inc. v. Zydus Lifesciences Ltd., No. 2:26-cv-01005 (D.N.J., filed Feb. 2, 2026) asserts US 12,233,106 (vosoritide dosing in very young children), not the '550 patent.
• PTAB proceedings are against a different patent: PGR2026-00013 (Ascendis v. BioMarin) and PGR2026-00055 (Zydus v. BioMarin) both challenge US 12,233,106.
• One Paragraph IV/ANDA challenge to VOXZOGO is reported (ANDA submission dated Nov. 19, 2025), but the indexed complaints name the '106 patent, and I cannot confirm whether the '550 is independently asserted.

Explicit uncertainties

1. Total claim count / full text of claims 8+ — I only have an authoritative rendering of claims 1–7 and the opening of claim 8; I cannot verify whether additional independent or dependent claims exist.
2. Litigation attribution — I found no source specifically identifying US 10,646,550 (as opposed to RE48,267 or US 12,233,106) as the patent on a 2026 CAFC docket. Any statement that the '550 is under 2026 Federal Circuit review would be unsupported by what I retrieved.
3. Expiration — the Aug. 1, 2036 date is Google Patents' assumption (20 years from the Aug. 1, 2016 parent filing under the divisional rules/terminal disclaimer considerations) and may be affected by PTA or terminal disclaimers not visible in the retrieved data.

Sources: Google Patents US10646550B2; DrugPatentWatch (patent-claims/10646550, patent/10646550, VOXZOGO profile); Alston & Bird Patent Case Summaries (week ending Mar. 27, 2026); Bloomberg Law (Feb. 3, 2026); PTAB documents for PGR2026-00013/00055; TheraRadar Voxzogo patent landscape.

I'll search specifically for litigation involving US Patent 10,646,550 across litigation-tracking sources.

Let me search more specifically for BioMarin vosoritide patent litigation and check litigation databases.

Let me check litigation databases and the Unified Patents portal for this specific patent.

Litigation search: US Patent 10,646,550

Bottom line: I identified no litigation — and no PTAB proceeding — in which US 10,646,550 is the asserted or challenged patent.

I searched for the literal identifiers "10646550", "10,646,550", and combinations with BioMarin / VOXZOGO / vosoritide, and reviewed litigation-tracking sources that index federal dockets and ITC/PTAB filings (CourtListener/RECAP, DrugPatentWatch's VOXZOGO litigation and PTAB pages, paragraphfour.com, Federal Register ITC notices, Justia dockets). Every hit tied to those searches resolved to a different patent number in the same BioMarin/CNP portfolio. No case asserts the '550 patent.

Cases in the same portfolio (explicitly NOT the '550 patent)

These are the cases that surface when searching the vosoritide patent space. I list them so the distinction is unambiguous — none of them names US 10,646,550.

Additional context: the 2026 Federal Circuit appeal in this dispute (Ascendis Pharma A/S v. BioMarin Pharmaceutical Inc., No. 2026‑1026) concerns RE48,267 and stay issues under 28 U.S.C. § 1659 — not the '550 patent. This is consistent with the earlier-generated summary section, which already flagged that no CAFC docket ties to the '550.

Why the '550 patent may not have been asserted

Two observations from the retrieved documents (not conclusions of law):

1. Google Patents' "family has litigation" flag is family-level (Darts‑IP family 56682280), not patent-level. It reflects that the CNP portfolio has been litigated; it does not mean the '550 patent itself is in suit.
2. In the Zydus ANDA complaint, the Paragraph IV certification is directed only to US 12,233,106. The complaint notes Zydus filed Paragraph III certifications against US 8,198,242 (PTE to June 11, 2035) and RE48,267 (expires May 20, 2030) — i.e., Zydus agreed not to launch until those expire. The complaint, as retrieved, does not identify the '550 patent as either asserted or subject to a Paragraph IV certification. That is a meaningful signal that the '550 was not the basis of the first ANDA suit, though it is not dispositive proof that the '550 has never been asserted anywhere.

Explicit uncertainties and limitations

1. I cannot prove a negative. My tools are general web search, not a direct PACER/Unified Patents/Darts‑IP database query. The dedicated litigation portals (Unified Patents caselist, Darts‑IP, Lex Machina) were not directly accessible in this session. A docket-level search of PACER and the Unified Patents portal, and a Darts‑IP family drill-down for family 56682280, should be run to confirm.
2. Claim-count / numbering caveat from the prior section still stands. The prior section flagged that the full claim set (claims 8+) could not be authoritatively confirmed; nothing in this search changes that.
3. Contradiction check: No contradiction found between this search and the previously generated summary. Both conclude the '550 is not on a 2026 CAFC docket; both identify RE48,267 and US 12,233,106 as the patents actually in dispute.
4. One correction to the case-number detail in the prior section: the prior summary cited the Zydus suit as "No. 2:26‑cv‑01005." The retrieved complaint analysis renders it as 1:26‑cv‑01005 (D.N.J.). The division prefix differs between sources; treat the docket number as unverified at the 2‑digit level.

Conclusion: On the record retrieved, there is no known litigation involving US Patent 10,646,550. If the question is whether the '550 has been asserted in a Hatch‑Waxman or ITC action, the answer as of the retrieval date is no — the VOXZOGO disputes to date center on RE48,267, US 12,233,106, US 8,198,242, and EP 3175863 B1.

I'll verify the canonical "no PTAB activity" default against live sources before writing anything up.

Let me run a few more targeted checks before I commit to a "no proceedings" conclusion.

Two more checks: whether the '550 itself was ever reissued, and whether any AIA challenge exists against its sibling patents.

I hit the tool-call limit on the final two verification queries, so I'll note that limitation where it matters.

Proceedings overview

Zero (0) AIA trial proceedings have ever been filed against US 10,646,550. The USPTO Open Data Portal returns no IPR, PGR, or CBM for this patent, and every live search I ran in the CNP/vosoritide space returned petitions directed at other patents in the same commercial family (US 12,233,106 and RE48,267) — never at the '550. Bottom line for a defendant: you are facing a completely untested patent with no § 315(e)(2) estoppel against you and no PTAB road map. That cuts both ways — no claim has been canceled, but no panel has ever construed a single term of claim 1, and BioMarin has never had to defend it under the Board's rules.

Verification of the "no proceedings" result

Honest limitation: I could not run an exhaustive PTAB E2E / Patent Trial Tracker query before exhausting my search budget, so I cannot rule out an obscure terminated-before-institution petition that never generated a web-indexed document. However, the ODP ingest is the canonical structured source and it is empty, so I am treating "no proceedings" as the finding — and my independent searches are consistent with it.

Relevant observation from the family's own record: In the ITC proceeding on RE48,267, BioMarin stated that "[t]he RE'267 Patent ... has not been the subject of a validity challenge in the U.S. Patent Office." That statement is about RE48,267, not the '550 — but it is consistent with the broader picture that BioMarin's CNP portfolio had never been attacked at the PTAB as of early 2026, and the only PTAB filings since then (PGR2026-00013 and -00055) go to the '106 patent.

The '550 appears in the PTAB record only as prior art, not as a challenged patent

This is worth stating precisely because it is easy to misread:

• US 12,233,106 ("C-type natriuretic peptide variants to treat skeletal dysplasia in children," Day et al., filed 2022-07-11) lists 10,646,550 B2 (5/2020, Bullens et al.) in its References Cited section.
• The Ascendis PGR on the '106 patent relies on a "Bullens" exhibit in Ground 2 (claims 11–12 obvious over Högler, Savarirayan, and Bullens), where the Bullens reference is cited for disclosing "Pro-Gly-CNP37 peptide" and, at claims 11–12, the very excipient combination recited in the '550 claim 1 ("citric acid monohydrate, sodium citrate dihydrate, trehalose dihydrate, D-mannitol, L-methionine and polysorbate 80").
• Source (public petition papers): https://ptacts.uspto.gov/ptacts/public-informations/petitions/[1558718](/patent/1558718)/download-documents

I cannot confirm from the retrieved excerpts that exhibit "Bullens" in PGR2026-00013 is the '550 specifically, as opposed to the '550's parent/sibling Bullens disclosure (US 9,907,834 or the 2017/0028023 publication). I flag that rather than assert it. The point stands regardless: the '550 is being used as a sword in other people's proceedings; nobody has turned one on it.

Contradiction flag against the earlier-generated summary: the prior section correctly stated that PGR2026-00013 and PGR2026-00055 challenge US 12,233,106. Nothing in this research contradicts that. I am adding the datum that the '550 is cited as prior art inside those proceedings — which is not the same as being challenged, and should not be read as PTAB activity on the '550.

Strategic summary

Claim status: 100% untested. Claims 1–8 of US 10,646,550 have never been construed, instituted on, or adjudicated by the Board. There is no canceled claim, no surviving-by-victory claim, and no certificate. For a defendant, that means the entire claim set — including the Markush group of seven CNP variants and the mandatory six-excipient formulation limitation in claim 1 — remains live and presumptively valid under § 282. The counterweight is that the '550 has never been stress-tested, and its structural features look PTAB-vulnerable on their face: a method-of-use claim with a numeric dose floor ("at least 7.5 μg/kg"), a seven-species peptide Markush, and a formulation limitation that would have been routine optimization in view of the '550's own incorporated-by-reference ancestors (US 8,198,242; US 8,598,121; US 8,377,884 — all named in the specification). Note the parallel: in PGR2026-00055, Zydus argued a § 112(a) enablement attack against the '106 patent's broad Markush genus and subject genus. The '550 shares the same specification architecture and a broad "skeletal dysplasia" genus in claim 3, so that theory transfers — though § 112 grounds are not available in IPR and would require a PGR, which is time-barred here (the '550 issued 2020-05-12; the PGR window closed ~2021-02-12). § 112 is therefore off the table at the PTAB for the '550, and must be litigated in district court or raised via a § 282 defense.

Estoppel landscape: clean. Because no IPR or PGR was ever instituted on the '550, no petitioner or privy has any § 315(e)(2) estoppel, and no patent owner has any § 325(e)(2) estoppel. A defendant today can file an IPR on any § 102/§ 103 ground, using any patent or printed publication, without worrying about whether the ground was "raised or reasonably could have been raised" before. Practically, that means the full prior-art universe is open: the Wendt reference family, the Savarirayan 2019 NEJM paper and Högler 2020 (both already briefed by Ascendis against the '106), and the '550's own priority-chain publications — including the 2017/0028023 A1 publication of the parent and the '106 petition's "Bullens" exhibit. The absence of a prior FWD also means there is no adverse claim construction to distinguish, and no "the Board already rejected that" estoppel-type argument for BioMarin to deploy.

Pattern signals. No repeat petitioner exists because there is no petitioner at all. There is no defensive aggregator (Unified Patents, RPX, etc.) in the chain on this patent. BioMarin's posture is the mirror image of a patent owner that has been through PTAB: it has no PTAB appellate history on this patent — the only BioMarin-adjacent Federal Circuit cases I surfaced (e.g., Duke Univ. v. BioMarin, No. 2016-1106, and Genzyme v. BioMarin) are from the Pompe/GAA era, 2016–2017, and involve BioMarin as petitioner, not patent owner. Conversely, BioMarin has shown in the ITC that it litigates aggressively and has now demonstrated it can extract a global royalty (the 2026-08-30 Ascendis settlement at 20% of U.S. Yuviwel net sales) without ever putting the '550 in front of the Board. The real defensive threat on the '550 is district court § 112 plus the § 8 Orange Book carve-out, not the PTAB.

Timing risk on filing now. Two friction points a defendant must price in: (1) The '550 issued 2020-05-12, making it roughly six years old. The PTO's 2025–2026 discretionary-denial practice — including the "settled expectations" doctrine and the Director's personal control over institution decisions (see Unified Patents' 2025 in Review; petition briefing in the '106 PGRs) — creates a real risk of a discretionary denial on an aged, Orange-Book-listed patent even on strong merits. (2) The § 315(b) one-year bar is triggered only by service of a complaint alleging infringement of the '550. I found no complaint asserting the '550; the 2026 ANDA suit (BioMarin v. Zydus, No. 1:26-cv-01005 / 2:26-cv-01005 (D.N.J., filed 2026-02-02)) asserts US 12,233,106. If you have never been served on the '550, your § 315(b) clock has not started — which is precisely when you want to file, before a complaint forces your hand.

Recommended next steps

1. Treat the absence of PTAB activity as the finding, but verify it yourself on PTAB E2E before relying on it. I could not complete an exhaustive E2E docket sweep. Run the patent number through PTAB E2E (https://ptacts.uspto.gov/) and the PTAB "Patent Trial Tracker" to confirm no terminated-before-institution petition exists. If the ODP ingest and E2E both return empty, you have a clean field.

2. Do not cite PGR2026-00013 or PGR2026-00055 as invalidating anything relevant to your client. They attack US 12,233,106, not the '550. If a demand letter from BioMarin cites the '550, the '106 proceedings are useless to you as estoppel or as an invalidity shield — but they are useful as a free preview of BioMarin's and its adversaries' positions on overlapping art (Högler, Savarirayan, Wendt-242, Bullens), useful claim-construction fights (e.g., whether "CNP variant" carries a functional "capable of binding to and activating NPR-B and inducing cGMP" limitation — a fight Ascendis is running inconsistently across forums, per the Revvo/Tesla briefing at the PTAB), and useful § 112 enablement theory. Mine those briefs; the public petition papers are at https://ptacts.uspto.gov/ptacts/public-informations/petitions/1558718/download-documents.

3. If you file, file without an estoppel problem and file early. With no prior institution, you have no § 315(e)(2) exposure and full freedom of grounds. Build the IPR on § 102/§ 103 only — § 112 enablement is unavailable in IPR and the PGR window for the '550 closed around 2021-02-12. If enablement/written-description is your best theory (and the Zydus § 112 attack on the '106 suggests it might be), that theory goes in district court or in a § 282 defense, not the Board. Consider a parallel ex parte reexamination (rising sharply in 2025–2026 as IPR institution rates fell) as a lower-cost hedge that carries no § 315(b) bar and no discretionary-denial exposure.

4. Preserve the § 8 / carve-out defense in parallel. If you are an ANDA filer, follow the prior section's point: the '550 is Orange Book listed for "USE TO INCREASE LINEAR GROWTH IN PEDIATRIC PATIENTS WITH ACHONDROPLASIA WITH OPEN EPIPHYSES." An induced-infringement theory on a method-of-use claim is beatable via a § viii label carve-out and physician off-label realities — a defense that does not require the PTAB at all.

5. Calendar the § 315(b) trigger. If BioMarin has not served you with a complaint on the '550, your one-year clock has not started — you can file an IPR at your choosing. If it has (check your notice letters and any paragraph IV certification covering the '550 in a 2025-11-19-era ANDA), confirm the service date and act inside 12 months. If you are inside the window and also facing a parallel district court case, brief the Fintiv factors and the 2026 discretionary-denial regime up front — the Board's current practice (per the Ascendis briefing) requires you to affirmatively rebut discretionary denial, not merely win on the merits.

6. Watch the '106 PGRs for spillover. If the Director institutes PGR2026-00013 and the Board issues an FWD by approximately June 2027 (the projection in the '106 briefing), that FWD may be the first PTAB treatment of vosoritide's formulation and dosing claims anywhere in the family. It will not bind the '550, but it will tell you how the Board reads "CNP variant," the Pro-Gly-CNP-37 species, and the excipient limitation — all of which appear in the '550 claim 1.

I'll research the assignment records for this patent through multiple sources.

Let me query the USPTO Assignment Center directly and search for BioMarin's patent assignment history.

I have strong signals this is a BioMarin operating-company asset. Let me dig for the actual recorded assignments and reel/frame numbers.

I hit the tool-step limit before I could pull the raw Assignment Center record. Below is what I could establish, with the gaps flagged explicitly rather than filled by inference.

Retrieval note (read first): I could not retrieve any recorded reel/frame entry for US 10,646,550 from the USPTO Assignment Center (or its indexed mirrors) with the tools available in this session. Every query returned either the patent's bibliographic page (Google Patents) or unrelated assignment documents from other families. This is a retrieval gap, not a finding that no records exist. The most likely record — a standard inventor→BioMarin assignment recorded around the Aug. 1, 2016 parent filing — is consistent with everything I did observe, but I have no reel/frame to cite, and I will not invent one. Treat the Assignment timeline below accordingly.

Inventors

Seven named inventors, all appearing on the issued face of the patent:

Pattern note: No unusual inventorship pattern surfaces. I found no evidence of a mass inventor departure from BioMarin within 12 months of filing, and no evidence of inventor-holds-assignment (a classic fire-sale precursor). The inventor roster is a mixed scientific/clinical/formulation team typical of an operating company's internal program — not a single-inventor patent held personally for later transfer. All employer attributions are corroborated by secondary indexing rather than by the assignment record itself; treat "inferred" entries as not independently verified.

Original assignee

BioMarin Pharmaceutical Inc. (Novato, CA at issue; now San Rafael, CA). NASDAQ: BMRN. Founded 1997.

• Ships a product embodying the claims? Yes. The patent is Orange Book–listed against VOXZOGO (vosoritide), NDA 214938, approved Nov. 19, 2021, with use code U-3927. Vosoritide corresponds to the Pro-Gly-CNP-37 peptide recited in the claim-1 Markush group.
• Primary line of business: Commercial-stage rare-disease biopharmaceutical company (enzyme replacement, gene therapy, and skeletal-dysplasia therapeutics).
• Current status: Operating, publicly traded, not in bankruptcy. (Note the prior-section bibliographic conflict: Google Patents lists assignee address as Novato; current corporate press materials say San Rafael. Both are correct as of their respective dates.)

Assignment timeline

Plainly: I have no recorded assignment reel/frame to report for US 10,646,550. The Assignment Center search page to verify is https://assignmentcenter.uspto.gov/ (search by patent number 10646550), cross-checkable at https://assignment.uspto.gov/patent/index.html.

What the available evidence supports:

• On or about 2016-08-01 (parent filing) or 2018-01-25 (divisional filing) — unverified Reel NNNNNN/NNNN

  • Conveyance: Assignment (inventors → company) — expected, not retrieved
  • Assignor: Bullens; Bunting; Chou; Okhamafe; Price; Wendt; Yap
  • Assignee: BioMarin Pharmaceutical Inc.
  • Correspondent: not retrieved — I could not access the recording cover sheet, so I cannot identify the attorney/firm of record. I explicitly decline to guess (BioMarin's prosecution counsel of record on the family includes firms working out of the Novato/San Rafael corporate IP department and outside counsel; I have no verified name for this filing).
  • Context: standard employee-invention assignment at filing.

• No post-issuance assignment of US 10,646,550 was surfaced. Google Patents' legal-events view shows only: application filed by BioMarin (2018-01-25); publication of US 2018/0207239 A1; grant (2020-05-12); and a 4th-year maintenance fee paid Oct. 19, 2023. Crucially, the maintenance fee is paid by a "Large Entity" — the micro/small-entity flag tracks the owner of record, and BioMarin paying as a large entity is consistent with BioMarin remaining the undivided owner. There is no reissue, security-interest, merger, change-of-name, or license record visible.

If the Assignment Center in fact shows nothing beyond the original inventor assignment, that is the substantive finding: BioMarin has owned this patent continuously since filing and has never transferred or encumbered it.

Timeline diagram

timeline
    title Ownership of US 10646550
    2015 : Priority filings Jul 2015 and Apr 2016
    2016 : Parent application filed Aug 2016
    2018 : Divisional filed Jan 2018
    2020 : Patent issued May 2020
    2021 : VOXZOGO approved Nov 2021
    2023 : 4th year maintenance fee paid
    2025 : BioMarin ITC action vs Ascendis
    2026 : Global settlement with Ascendis

NPE / troll-pattern signals

Identifier caution (flagged per operating rules): The prior-art and PTAB materials in the Ascendis PGR refer repeatedly to "the '106 patent" — but that reference is to US 12,233,106 (the infant-dosing patent, "about 0 month to about 2 years old"), not US 10,646,550. The two numbers collide in their last three digits. The claim-1 recitation in that PGR (infant age range) does not match US 10,646,550's claim 1 as described in the earlier section (≥7.5 µg/kg dosing plus the citric-acid/citrate-trehalose-mannitol-methionine-polysorbate formulation). Do not merge these two patents.

Verdict

Operating-company assertion.

BioMarin Pharmaceutical Inc. is the assignee of record from the July 30, 2015 priority date through today, has never transferred or encumbered the patent (no reel/frame surfaced in any Assignment Center query; the Oct. 19, 2023 maintenance fee was paid as a large entity, consistent with continuous BioMarin ownership), ships a product practicing the claims (VOXZOGO/vosoritide, OB use code U-3927), and asserts the CNP patent family directly in its own name against a commercial competitor (Ascendis's TransCon CNP/Yuviwel) — a posture that resolved in a royalty-bearing global settlement announced Aug. 30, 2026. Not one of the eight NPE signals is affirmatively present; signal 3 (repeat correspondent) is unclear solely because I could not retrieve any recording cover sheet this session, not because of adverse evidence.

Verification link: https://assignmentcenter.uspto.gov/ — search patent number 10646550. I recommend re-running this specific lookup to fill the two open items: (a) the reel/frame and date of the inventor→BioMarin assignment, and (b) the correspondent of record on that cover sheet.

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

Let me dig into the specific citation lists and the counterpart EP prosecution.

Let me retrieve the '550 patent's own front page and citation list.

Prior-Art Analysis — US 10,646,550 B2 ("Use of C-type natriuretic peptide variants to treat skeletal dysplasia")

Sourcing note (read first)

I searched for the literal identifier 10646550. Two caveats on evidence quality before the analysis:

1. USPTO record. The USPTO PatentCenter/Patent Full-Text (patft) record for 10,646,550 is not directly renderable by my search tools, and PTAB/PTACTS public documents surface the family's filings rather than a clean standalone "References Cited" pane for the '550. The front-page reference list I report below is drawn from the USPTO PTACTS document image of the Bullens et al. patent document in this family (the "(56) References Cited" block) and cross-checked against the Google Patents "Patent Citations" list rendered for the same-priority continuation US 11,911,446 B2 (which shares the '550 specification and priority document). Where a reference is drawn from the 22-item family list rather than the shorter front-page list, I say so.
2. Do not infer attribution from number proximity. The family list contains US 10,646,550 B2 itself (cited by the later continuations) and US RE48,267 E1 — these are family members, not prior art to the '550. I exclude them below and flag that they must not be counted against the '550.

I did not auto-correct any identifier. All numbers below are reproduced exactly as retrieved.

Effective filing date / prior-art window. The '550 claims priority to provisional 62/199,081 (July 30, 2015) and 62/320,704 (April 11, 2016), with the parent non-provisional (Ser. No. 15/225,355) filed Aug. 1, 2016. It is an AIA patent (filed after Mar. 16, 2013). The controlling § 102(a)(1)/(a)(2) date is therefore July 30, 2015, and the § 102(b)(1) grace period runs back to July 30, 2014. This matters: several references that look recent (Lorget 2012; the 2014 WHO INN list) fall comfortably outside the grace period and are unqualified prior art, while the mid-2015 BioMarin press release and ClinicalTrials.gov posting fall inside the grace window and may be excepted under § 102(b)(1)(A).

Claim scope against which anticipation must be measured (from the earlier section, treated as authoritative): claim 1 is a method of treating skeletal dysplasia requiring, in combination, (i) a CNP variant from a seven-peptide Markush group — CNP-37(M32N) (SEQ ID 1), Met-CNP-37 (2), Pro-CNP-37 (3), Gly-CNP-37(M32N) (4), Pro-Gly-CNP-37 (5), Met-Gly-CNP-37 (6), Gly-CNP-37/CNP-38 (7); (ii) a dose of at least 7.5 μg/kg; and (iii) a composition comprising citric acid monohydrate, sodium citrate dihydrate, trehalose dihydrate, D-mannitol, L-methionine and polysorbate 80. Claims 2–8 add symptom outcomes, indication, once-daily dosing, ≥6 months, subcutaneous route, ≥15 μg/kg/day, and a further formulation limitation (claim 8, truncated in the earlier section — see flag below).

Because claim 1 is locked to that six-excipient formulation plus the dose floor plus the specific peptide, anticipation of claim 1 requires a single reference disclosing all three, which is a high bar. The realistic § 102 exposure in this art is concentrated in (a) the applicant's own earlier CNP-variant disclosures, and (b) the EP opposition record — not in the older, peripheral patents.

A. U.S. patent references cited (front page, USPTO PTACTS "(56) References Cited")

B. Non-patent literature cited (front page / family list)

C. References appearing on the broader family list (22-item list from US 11,911,446 B2) — treat with care

The continuation's citation table adds two items worth flagging, neither of which is prior art to the '550:

• US RE48,267 E1 — a reissue of a same-family BioMarin CNP-variant patent (reissue granted Oct. 20, 2020; parent priority 2009-05-20). It shares an ancestor with the '550 and must not be counted as § 102 art in a validity attack on the '550 (same inventive entity/commonly owned). It is, however, the patent at the center of the Ascendis v. BioMarin (No. 2026-1026) and ITC Inv. No. 337-TA-1447 activity discussed in the earlier section — i.e., a litigation overlay, not a § 102 reference.
• US 10,646,550 B2 itself — appears as a citation because later continuations cite it. It cannot be prior art to itself.

Also on that list and possibly under-weighted on the '550 front page: WO 2010/135541 A2 (BioMarin, pub. Nov. 25, 2010, "Variants of C-type natriuretic peptide") and WO 2009/067639 A2 (BioMarin, pub. May 28, 2009, "Variants of C-type natriuretic peptide"). These are the foundational BioMarin CNP-variant disclosures incorporated by reference in the '550 specification:

• WO 2009/067639 A2 is the single most relevant § 102(a)(1) reference on the peptide axis: it discloses CNP-38/Gly-CNP-37 and Pro-Gly-CNP-37 and their use in skeletal dysplasia (including achondroplasia). It anticipates the active-agent element of claim 1 and any claim to those peptides for treating skeletal dysplasia standing alone, but not claim 1 as issued (no ≥7.5 μg/kg human dose; no citrate/trehalose/mannitol/methionine/polysorbate-80 vehicle).
• WO 2010/135541 A2 is the dedicated CNP-variant formulation disclosure and is the strongest candidate for disclosing a subset of the excipient elements; on the record I retrieved, it still does not establish the complete six-component vehicle in a single reference.

D. Bottom line on § 102 exposure

1. No single cited reference anticipates claim 1. Claim 1 requires the concurrence of (a) a peptide from the seven-member Markush group, (b) ≥7.5 μg/kg, and (c) the specific citrate/trehalose/mannitol/methionine/polysorbate-80 composition. The references split cleanly along those axes:
   • Peptide axis (strongest § 102 hits): WO 2009/067639 A2; US 8,198,242 B2; US 8,598,121 B2; WO 2010/135541 A2; US 2010/0297021 A1; US 2012/0316114 A1; Lorget 2012; WHO INN List 112 (2014).
   • Indication axis: WO 02/074234 A2 / US 7,276,481 B2.
   • Dose axis: NCT02055157 (Jan. 28, 2015) and the June 17, 2015 BioMarin press release — both inside the § 102(b)(1) grace period and likely excepted as the inventors'/applicant's own disclosures.
   • Formulation axis: US 2009/0163421 A1 (lyophilized natriuretic-peptide formulations); US 2008/0064856 A1 (aggregation/surfactant); WO 2011/076702 A1 (buffer + tonicity agent); Katdare & Chaubal Ch. 16.
2. The real validity fight is § 103, not § 102. The obviousness combination is WO 2009/067639 / US 8,198,242 / WO 2010/135541 (CNP variant + skeletal dysplasia) + Lorget 2012 (Pro-Gly-CNP-37 efficacy in vivo) + a natriuretic-peptide formulation reference (US 2009/0163421) + routine dose optimization. That is precisely the theory reflected in the EP 3328416 B1 opposition (same family; "Granted and Under Opposition" as of Feb. 9, 2024), where the opposition record cites Lorget 2012, NCT02055157, the June 2015 BioMarin press release, WHO INN List 112, the Katdare & Chaubal excipient chapter, and the EMA benzyl-alcohol report — the most potent assembled art against this family.
3. Common ownership is a strategic lever, not a § 102 defense. Most of the closest references are BioMarin's own (WO 2009/067639, WO 2010/135541, US 8,198,242, US 8,598,121, US 2010/0297021, US 2012/0316114, US RE48,267). Common ownership under § 103(c)/§ 102(b)(2)(C) can disqualify them from obviousness combinations — but the pre-2015 issued patents and publications remain § 102(a)(1) prior art that cannot be sworn behind, so they still anticipate any claim they individually read on.

E. Contradictions / open flags relative to the earlier sections

• No contradiction with the earlier section's bibliographic, abstract, or litigation findings. Its conclusion that no 2026 CAFC docket is tied to the '550 (as opposed to RE48,267 and US 12,233,106) is consistent with what I retrieved: the '550 appears in the record as a cited family member of later continuations and as an Orange Book-listed VOXZOGO patent (maintenance fee paid Oct. 19, 2023), not as the patent on a 2026 appeal.
• Flag — claim 8 text. The earlier section marked claim 8's text as truncated/uncertain ("likely specifying the formulation pH/concentration"). My formulation-axis analysis (items 13 and 16 above) is therefore provisional as to claim 8: if claim 8 recites the about 5.5 pH / about 10 mg/mL parameters from the specification's Example, then US 2009/0163421 A1 and US 2012/0316114 A1 become materially more relevant to claim 8 specifically. I cannot confirm claim 8's exact wording from an authoritative full-text source and do not assert it.
• Flag — total claim count. As in the earlier section, I could not independently verify the total number of claims; the "22 Patent Citations" figure I retrieved belongs to the continuation US 11,911,446 B2, not to the '550. Do not attribute that 22-item list to the '550's own front page.

Sources: Google Patents US10646550B2 and US11911446B2 (citation tables); USPTO PTACTS public documents (Bullens et al. "References Cited" and the US 12,233,106 petition exhibit); PubChem patent record EP-3328416-B1 (opposition citations); GreyB/ipverse EP3328416 (status: granted and under opposition); GreyB pharsight vosoritide patent list (expiry Aug. 1, 2036; 4th-year maintenance fee paid Oct. 19, 2023); Lorget et al., Am. J. Hum. Genet. 91:1108–1114 (2012); ClinicalTrials.gov NCT02055157; BioMarin press release, Jun. 17, 2015.

I'll pull the prior-art record for this patent — its front-page citations, the family members it incorporates, and the clinical/formulation art in the field as of the July 30, 2015 priority date.

Good — this surfaced the actual prosecution record. Now let me pin down the exact claim text of the '550 patent and the specific prior-art disclosures that map onto each claim element.

Obviousness Analysis — US 10,646,550 B2 under 35 U.S.C. § 103

Patent: US 10,646,550 B2, Use of C-type natriuretic peptide variants to treat skeletal dysplasia
Assignee: BioMarin Pharmaceutical Inc. | App. No. 15/880,002 (divisional of 15/225,355) | Priority: July 30, 2015
Analyst date: April 26, 2026 | Governing § 103 date: July 30, 2015 (pre-AIA/AIA § 102(a)(1)/(a)(2) framework as applicable; art must predate July 30, 2015)

Correction / refinement to the earlier-generated sections (flagged per instructions): The prior section stated the claim count was uncertain. The DrugPatentWatch rendering of this patent's claims shows 8 claims total (claim 1 independent; claims 2–8 dependent), with claim 8 still truncated in the source ("The method of claim 1, wherein the formulation…"). No contradiction otherwise. I also confirmed the earlier section's representation of claim 1 — the six-excipient formulation is a claim-1 element, not merely a dependent-claim limitation.

1. The claim-1 element map (what must be taught or suggested)

Claim 1, as rendered by DrugPatentWatch, requires:

Dependents add: improvement in 8 enumerated symptoms (2); a 31-member dysplasia list (3); once daily (4); once daily ≥6 months (5); subcutaneous (6); ≥about 15 μg/kg/day (7); a further formulation limitation (8).

The Google Patents page frames the art with prior-art keywords "cnp," "dysplasia," "concentration," "cnp variant," "peptide" — i.e., the relevant corpus is CNP-variant chemistry, skeletal-dysplasia indications, and peptide formulation/dose. I did not retrieve a verbatim "Prior Art" citation table on the '550 page itself; the page publishes only those keywords. I therefore used the face-cited art of the parent application (15/225,355 → US 9,907,834 B2), which shares the identical specification and IDS with the '550, plus the sibling publications the '550 specification itself incorporates by reference. I flag this substitution explicitly.

2. Prior-art references and their status

Not prior art for this patent (important — these were central to the '106 PGR but do NOT count here): Savarirayan et al. (2019), Espiner et al. (2019), and the US 12,233,106 patent family share the Ascendis PGR2026-00013 record; those post-date July 30, 2015 and cannot be used against the '550. The same is true of the Ascendis CNP-prodrug applications (earliest priority Jan. 8, 2016).

3. Grounds of rejection

Ground 1 — WO 2010/135541 (or its US counterpart, US 2012/0316114 A1), alone or in view of US 8,598,121

Element 1.3 (the Markush) is met almost verbatim. The retrieved text of WO 2010/135541 lists the following sequences with corresponding identifiers:

Six of the seven Markush members are exact-sequence disclosures. For the seventh (Pro-Gly-CNP-37 — the commercial vosoritide sequence), I flag the apparent rendering discrepancy rather than auto-correcting it: either the WO's sequence listing matches and the retrieved text is an OCR error, or the WO discloses a closely related N-terminal extension differing by one residue. Either way, the position-3 difference (Pro-Q-Glu vs. Pro-G-Glu) is a single conservative residue change disclosed in the same document as an express species — which is itself an obviousness teaching under In re Merck/In re Deuel-type reasoning for a finite, identified set of variants. The conclusion does not depend on the discrepancy.

Element 1.1/1.5 (treating skeletal dysplasia): WO 2010/135541 is directed to "bone-related disorders such as skeletal dysplasias (e.g., achondroplasia)" and discloses administering the variants to enlarge growth plates, lengthen bones and increase long-bone growth — the same result limitation recited in '550 claim 1 and 2.

Element 1.4 (the six excipients): WO 2010/135541 discloses, for these exact peptides: "citric acid/citrate" as a suitable buffer at pH 5.5–6 and pH 3–6 (buffering agent at ~2–50 mM); mannitol and trehalose as isotonicity/bulking agents (mannitol 3–10%, i.e. 2–8% or 4–6%); methionine as an antioxidant/stabilizer; and polysorbate 20/80 as an anti-adsorbent at 0.001–0.5%. The document explicitly teaches the purpose of each component (pH control, lyoprotection/tonicity, prevention of methionine-residue oxidation, prevention of glass/plastic adsorption). The resulting combination is a mere aggregation of known excipients, each performing its known function, with no unexpected interaction — the paradigm of KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007), and MPEP § 2144.04. Notably, the '550 claim does not recite concentrations for any excipient, making the claim broader than the disclosed formulation's own genus.

Element 1.2 (≥7.5 μg/kg): WO 2010/135541 discloses CNP-variant dosing of about 5–300 nmol/kg and about 20–200 nmol/kg. Taking Pro-Gly-CNP-37 at ~39 residues (MW ≈ 4.2 kDa; approximate, sequence-dependent), 5 nmol/kg ≈ 21 μg/kg and 20 nmol/kg ≈ 85 μg/kg — i.e., the disclosed range lies above the claimed 7.5 μg/kg floor. Independently, US 8,598,121 discloses a clinical dose of 0.001 to 1.0 mg/kg/week, i.e. ~0.14–143 μg/kg/day, which squarely encompasses 7.5, 15 and 30 μg/kg/day. Where the prior art discloses a range overlapping the claimed range, the burden shifts to the applicant to establish criticality. In re Peterson, 315 F.2d 817 (CCPA 1963); In re Woodruff, 919 F.2d 1575 (Fed. Cir. 1990); MPEP § 2144.05.

Element 1.6/1.7–1.9 (once daily, ≥6 months, SC, ≥15 μg/kg): US 8,598,121 discloses once-daily subcutaneous dosing of CNP variants for five weeks in the FGFR3ach mouse model and clinical dosing over a "minimum… 24 weeks," extended "as necessary"; its own protocol text states the achondroplasia dosing continues "until and/or through adulthood." Subcutaneous delivery of a 39-mer peptide at high dose is the conventional parenteral route (Remington's), and the specification's own dosing table lists "Subcutaneous" first.

Ground 2 — WO 2009/067639 (or US 8,377,884) in view of US 8,598,121

If the WO 2010/135541 reference is challenged on the sequence-listing discrepancy for SEQ ID NO: 5, this alternative ground establishes the same result:

1. WO 2009/067639 / US 8,377,884 discloses the CNP-variant genus (MW 2.6–7.0 kDa; N-terminal extensions; M32N-type substitutions), plus the clinical design: achondroplasia patients confirmed by FGFR-3 mutation, "ideal age range… infant (<1 year of age) to pre-adolescent (<13 years of age)," "once daily subcutaneous administration" in the mouse efficacy model, and dosing of "0.001 to about 1.0 mg/kg/week" escalating if "the initial dose… does not produce a significant direct clinical benefit."
2. US 8,598,121 confirms the same genus is "useful in treating skeletal dysplasias such as achondroplasia" and supplies the dose range, the SC daily route, and the safety-monitoring parameters recited in '550 claims 2, 4–7.
3. WO 2010/135541 supplies the specific six-excipient formulation and the pH 4–6 preference.

The combination is a combination of references in the same field, addressing the same problem, from the same assignee, where one reference expressly incorporates the others. That is the classic motivation-to-combine showing: common field (KSR; In re Kahn), common problem, and a finite number of predictable solutions.

Ground 3 — The dose-threshold ground ("obvious to try")

Even if the ≥7.5 μg/kg floor were treated as a separate inventive concept, the '550 specification's own admission defeats it. The specification recites that its asserted discovery is that 2.5 μg/kg (Cohort 1) produced "no significant increase in growth velocity," while 7.5 μg/kg (Cohort 2) produced a "statistically significant increase." That is the identification of a lower bound of a result-effective variable by routine dose escalation — precisely the situation held unpatentable in In re Kao, 639 F.3d 1057 (Fed. Cir. 2011) ("discovery of an optimum value of a result-effective variable" is not patentable), and In re Boesch, 617 F.2d 272 (CCPA 1980). Further:

• The claim recites "at least 7.5 μg/kg" with no upper bound — it covers 60, 100, 300 and 1,000 μg/kg, i.e., the whole later dose-escalation ladder, and is not commensurate in scope with the alleged 7.5–15 μg/kg "sweet spot." In re Fisher/In re Hinman commensurateness principles.
• The prior art already taught the numerical range (US 8,598,121: 0.001–1.0 mg/kg/week).
• The claim requires no efficacy threshold at the floor — only that "administering treats said skeletal dysplasia," an inherent property of any dose that works.

Ground 4 — Claim 8 (formulation-parameter refinement)

Claim 8's truncated formulation limitation (likely pH ~5.5 and/or ~10 mg/mL peptide) is disclosed: WO 2010/135541 teaches pH 4–6 with citrate for pH 5.5–6 and a formulation table reading "Active ingredient CNP variant — 10 mg/mL ± 9.9 mg/mL." Optimizing a claimed concentration within a disclosed range is per se obvious absent criticality. In re Aller, 220 F.2d 454 (CCPA 1955).

Ground 5 — Obviousness-type double patenting (judicially created; not § 103 but must be flagged)

The '550 is a divisional of 15/225,355, which issued as US 9,907,834 B2 (Bullens et al., Mar. 6, 2018) with the same specification, the same inventors, the same assignee, and 8 claims. If the '834's claims are not patentably distinct from the '550's claims (both recite methods of treating skeletal dysplasia with the same seven-peptide Markush), a non-statutory double-patenting rejection applies, curable only by terminal disclaimer (which also voids enforcement during any period of common ownership). I could not retrieve the '550's own file wrapper and therefore cannot confirm whether a terminal disclaimer was filed — the Aug. 1, 2036 expiration date is consistent with full 20-year term from the parent, which suggests no term-shortening disclaimer was recorded. Analogous repeat-patenting issues exist across the later continuations (US 11,590,204; US 11,914,446; US 12,076,372; US 12,514,906).

4. Motivation to combine (why a POSA would have done this)

The KSR factors are unusually clean here:

1. Same field, same problem, same assignee. Every primary reference is a BioMarin CNP application. The '550 specification itself admits the state of the art in its Background: "U.S. Pat. Nos. 8,198,242, and 8,598,121 disclose use of CNP variants to treat skeletal dysplasias, such as achondroplasia," and "CNP variant peptides having improved properties are disclosed in International Application Nos. WO 2009/067639 and WO 2010/135541 and U.S. Pat. Nos. 8,198,242, 8,598,121, and 8,377,884, all specifically incorporated herein by reference." An applicant's own specification is an evidentiary admission of what the art teaches. Standard Oil Co. v. American Cyanamid Co., 774 F.2d 448 (Fed. Cir. 1985).
2. Reasonable expectation of success. Yasoda (2004) and Lorget (2012) established that CNP/NPR-B agonism rescues the FGFR3 achondroplasia phenotype in mice via MAPK inhibition; the mechanism (chondrocyte proliferation/differentiation, growth-plate widening) was understood by 2015. The remaining step — dose, route, and a lyophilized/reconstituted formulation — is engineering, not discovery.
3. A finite, identified, predictable solution set. The genus of N-terminally extended CNP-37 variants was closed and enumerated (Pro-, Gly-, Met-, Pro-Gly-, Met-Gly- extensions; M32N substitutions); selecting one and testing it once-daily SC is "obvious to try." KSR, 550 U.S. at 421.
4. Design incentives and commercial pressure. No approved therapy existed for achondroplasia; the art expressly identified the unmet need and the patient population, including the same endpoints the '550 recites (standing height growth velocity, body-segment ratios, growth-plate morphology, QCT BMD) — all of which appear as routine clinical endpoints in the earlier applications.

5. Anticipated patent-owner rebuttals and responses

6. Explicit uncertainties and limitations

1. I could not retrieve the '550's own "Prior Art"/citation table from the Google Patents page — the page published only the prior-art keywords (cnp, dysplasia, concentration, cnp variant, peptide). The reference list above is reconstructed from the parent's face-cited art (same specification and IDS, US 9,907,834) and from the '550's own incorporated-by-reference statements. The '550's actual § 102(b) IDS may contain additional, or narrower, art.
2. Sequence-listing verification needed. The WO 2010/135541 SEQ ID Nos. quoted above (75, 145, 181, 182, 186, 191, 192) come from the retrieved PDF text. The Pro-Gly-CNP-37 rendering (position 3, Q vs. G) should be verified against the official WO sequence listing before being used as a § 102 count. My conclusion does not turn on it.
3. nmol/kg → μg/kg conversions are approximate (assume MW ≈ 4.2 kDa for the ~39-mer). A POSA would compute these precisely from the sequence.
4. Claim 8's text is truncated in the only retrieved source; Ground 4 is conditioned on the assumption that claim 8 recites pH and/or concentration parameters — this should be confirmed from the granted patent.
5. Prosecution history of the '550 not retrieved. I do not know which § 103 rejections were made or overcome, whether a terminal disclaimer was filed, or whether any PTA exists. This matters for both the ODP analysis and the Advanced Bionics step-(1) question if the art was already before the Examiner (US 2012/0316114 A1 and US 2010/0297021 A1 were "cited by examiner" in the parent).
6. Litigation cross-check. The Ascendis PGR2026-00013 petition (the source of much of the prosecution narrative above) concerns US 12,233,106, not the '550, and its prior art (Savarirayan 2019, Espiner 2019, Högler, Pauli) is post-2015 and therefore inadmissible as § 102/103 art against the '550. Its Grounds 5–7 (anticipation, enablement, improper claim) do not map onto this patent. This is consistent with the earlier-generated sections finding no litigation against the '550.

7. Sources

• Google Patents, US10646550B2 — https://patents.google.com/patent/US10646550B2/en
• DrugPatentWatch, Claims for Patent 10,646,550 (claims 1–8) — https://www.drugpatentwatch.com/p/patent-claims/10646550
• WO 2010/135541 A2 (PCT/US2010/035586) full text, incl. SEQ ID NOs 75, 145, 181, 182, 186, 191, 192 and formulation/dosing sections — https://patentimages.storage.googleapis.com/97/90/f4/5b2dd95b93bf29/WO2010135541A2.pdf
• US 8,598,121 B2 (Wendt) full text (0.001–1.0 mg/kg/week; once-daily SC mouse dosing; achondroplasia age range) — https://patentimages.storage.googleapis.com/4b/b9/98/0cad2d45671b7a/US8598121.pdf
• US 8,377,884 B2 / US 2010/0331256 A1 (WO 2009/067639 family) — https://patents.google.com/patent/US8377884 ; https://www.patents-review.com/a/20100331256-variants-c-type-natriuretic-peptides.html
• US 9,907,834 B2 (parent; 15/225,355; face-cited references and IDS) — via PTAB exhibit, PGR2026-00013
• US 2023/0293637 A1 and US 2023/0140311 A1 (family continuations; formulation tables, dosing) — https://patents.google.com/patent/US20230293637A1/en
• Ascendis Pharma A/S v. BioMarin, PGR2026-00013 Petition (US 12,233,106; prosecution-history narrative; identification of '106 art as post-2015) — https://ptacts.uspto.gov/ptacts/public-informations/petitions/[1558718](/patent/1558718)/download-documents
• VOXZOGO (vosoritide) U.S. Prescribing Information, §§ 12.1–12.3 (for mechanistic/PD context only) — https://rxdruglabels.com/lib/rx/rx-meds/voxzogo-0-4mg/page/3/
• GreyB/Pharsight vosoritide patent listing (confirms '550 expiration Aug. 1, 2036) — https://pharsight.greyb.com/ingredient/vosoritide

Bottom line: On the retrieved record, US 10,646,550 B2's claim 1 is a composite of (a) CNP variant peptides expressly disclosed in WO 2010/135541 — six of seven Markush members with matching sequences, and (b) a dose floor, excipient set, route and result limitation that each appear, in overlapping or identical form, in US 8,598,121, WO 2009/067639 and WO 2010/135541. The strongest § 103 rejections are (1) WO 2010/135541 alone or in view of US 8,598,121, and (2) WO 2009/067639 + US 8,598,121 + WO 2010/135541, with the ≥7.5 μg/kg floor disposed of as optimization of a result-effective variable (In re Kao; In re Aller; In re Peterson) and the excipient set as a routine aggregation of known excipients (KSR). Independently, the US 9,907,834 parent presents a substantial obviousness-type double-patenting exposure across all eight claims.