{ "vercy": "1.0-draft", "publication": { "status": "research-draft", "adjudicationStatus": "unreviewed", "publishableCanonical": false, "generatedAt": "2026-09-12T11:58:09Z", "providers": [ "Codex" ], "breadth": "recalled by Codex without web access - no source was read", "missingProviders": [], "pass": 2, "cost": { "grok": { "seconds": 21.7, "error": "Reading additional input from stdin...\nOpenAI Codex v0.153.4\n--------\nworkdir: R:\\02_PROJECTS\\02_Meta_Models_Platforms\\Ver.cy\\current\\thing-registry-backlog\nmodel: gpt-6-astra\nprovider: openai\napproval: never\nsandbox: read-only\nreasoning effort: none\nreasoning summaries: none\nsession id: 01a0957a-4025-7242-85f7-6ca3599cfac5\n--------\nuser\nDescribe what is already known about one registered thing. Answer as JSON only, no prose around it.\n\nThing: pegaptanib\nSense to describe: (none recorded)\nDomain code: PHY.MAT\nAlso known as: (none)\n\n\nContext for this batch of 1001 things:\n# Batch 044: 1001 regi", "usd": 0.0, "recall": true }, "codex": { "seconds": 77.0, "error": "Reading additional input from stdin...\nOpenAI Codex v0.153.4\n--------\nworkdir: R:\\02_PROJECTS\\02_Meta_Models_Platforms\\Ver.cy\\current\\thing-registry-backlog\nmodel: gpt-6-astra\nprovider: openai\napproval: never\nsandbox: read-only\nreasoning effort: none\nreasoning summaries: none\nsession id: 01a0957a-402b-7aa2-96e4-aff14cf8a003\n--------\nuser\nYou are drafting a Vercy meta-model for one registered thing. Answer as JSON only, no prose around it.\n\nThing: pegaptanib\nRegistry id: vr.tr.pegaptanib\nPlane / domain: PHY / PHY.MAT\nRegistry definition: (none recorded)\nNames folded into this entry: (none)\n\n\nCo" } }, "enrichment": { "pass": 3, "engine": "claude", "producedAt": "2026-10-06T12:00:00Z", "ingestedAt": "2026-10-06T08:52:10+00:00", "fields": [ "agent_conduct", "ethics", "failure_modes_and_hazards", "owners", "visual_identification" ] }, "gate": { "passed": true, "version": "1.0", "at": "2026-10-07T10:10:30+00:00", "evidence": [ "completeness 1.00", "sense: Wikidata description", "2 live sources", "review by codex: pass" ] } }, "metaModel": { "id": "THING-Q409935", "registryId": "vr.tr.pegaptanib", "name": "pegaptanib", "version": "0.1.0-research.1", "entryKind": "thing", "family": "Thing Registry", "domain": [ "PHY.MAT" ], "status": "research-draft" }, "canonicalUrl": "https://ver.cy/models/thing/q409935/", "model": { "registry_id": "vr.tr.pegaptanib", "name": "pegaptanib", "purpose": "Enable an agent to identify pegaptanib, assess the integrity and activity of a material sample, and determine which handling or use decisions its evidence supports.", "definition": "Pegaptanib is a pegylated, chemically modified RNA aptamer that selectively binds the VEGF165 isoform of vascular endothelial growth factor A and inhibits its activity, developed for intravitreal treatment of neovascular age-related macular degeneration.", "scope_statement": "This model owns vr.tr.pegaptanib in PHY / PHY.MAT: the modified, PEG-conjugated RNA aptamer substance, including its molecular identity, salt-form relationships, material quality, target-binding activity and handling constraints.", "in_scope": [ "Modified oligonucleotide sequence, terminal chemistry and PEG conjugation", "Distinction between pegaptanib active moiety, sodium salt and formulated material", "Sample composition, concentration, impurities and degradation", "VEGF isoform binding and functional inhibition under specified assay conditions", "Storage history, analytical evidence and substance-level use restrictions" ], "out_of_scope": [ "Macugen finished-product composition, packaging and commercial lifecycle", "Intravitreal injection procedures and delivery devices", "Patient-specific diagnosis, prescribing and treatment decisions", "Age-related macular degeneration and its clinical progression", "VEGF biology beyond the relationships needed to describe pegaptanib activity", "Manufacturing equipment and synthesis-process operation" ], "distinguishing_features": [ "Pegaptanib is a PEG-conjugated modified RNA aptamer; molecular identification must distinguish it from antibody fragments, fusion proteins and other VEGF inhibitors. [FDA Macugen label, 2011](https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021756s018lbl.pdf)", "Sequence, nucleotide modifications, terminal linkage and PEG attachment must match the reference identity; an unconjugated precursor or another RNA aptamer does not establish pegaptanib identity.", "Its characteristic target interaction involves the heparin-binding domain of VEGF165; an assay reporting only generic VEGF inhibition is insufficient to establish this specificity. [Primary binding study](https://pubmed.ncbi.nlm.nih.gov/16357200/)", "A pegaptanib sodium sample and a Macugen syringe represent a salt form and a finished product respectively; neither name alone establishes the composition or quality of an arbitrary pegaptanib sample." ], "characteristics": [ { "name": "Molecular identity match", "kind": "state", "unit_or_values": "verified match | partial match | mismatch | untested; reference and methods required", "why_it_matters": "Separates authenticated pegaptanib from sequence variants, precursors and unrelated aptamers." }, { "name": "Nucleotide and terminal chemistry", "kind": "category", "unit_or_values": "Position-resolved sequence, sugar modifications, backbone and terminal linkages", "why_it_matters": "Base sequence alone cannot identify the chemically modified substance." }, { "name": "PEG conjugation profile", "kind": "measurement", "unit_or_values": "Attachment-site identity, conjugated fraction in %, and PEG molar-mass distribution in g/mol", "why_it_matters": "Distinguishes intended conjugate from free PEG, unconjugated oligonucleotide and altered conjugation products." }, { "name": "Salt and identifier mapping", "kind": "relation", "unit_or_values": "Active moiety ↔ specified salt form ↔ verified CAS, PubChem or jurisdictional record", "why_it_matters": "Prevents identifiers and mass-based quantities from being transferred between chemically different representations." }, { "name": "Pegaptanib content", "kind": "measurement", "unit_or_values": "mg/mL or mg/g, with active-moiety or salt basis and analytical method", "why_it_matters": "Supports valid comparison of material quantities and assay inputs." }, { "name": "Purity and related substances", "kind": "measurement", "unit_or_values": "% by stated method; individual impurity concentrations with detection limits", "why_it_matters": "Resolves intact conjugate from oligonucleotide variants, degradation products and residual materials." }, { "name": "VEGF binding and inhibition", "kind": "measurement", "unit_or_values": "KD in mol/L; IC50 in mol/L or relative potency in %, with isoform and assay conditions", "why_it_matters": "Distinguishes binding affinity from functional inhibition and prevents unsupported comparisons between assays." }, { "name": "Material presentation", "kind": "state", "unit_or_values": "As-observed physical form; solvent, pH, ionic composition and temperature where applicable", "why_it_matters": "Connects analytical and stability results to the actual material tested." }, { "name": "Storage and excursion history", "kind": "state", "unit_or_values": "Temperature in °C, duration, light exposure, freeze-thaw count and evidence-backed disposition", "why_it_matters": "Helps determine whether prior quality and activity evidence still applies." }, { "name": "Material-use qualification", "kind": "category", "unit_or_values": "Research material | reference standard | qualified drug substance | other documented status | unknown", "why_it_matters": "Prevents chemical identity or purity alone from being treated as authorization for clinical use." } ], "affordances": [ "Compare a sample's sequence, modifications and conjugation profile against an authenticated pegaptanib reference.", "Resolve whether an identifier or quantity describes the active moiety, sodium salt or a finished formulation.", "Assess intact content and impurity evidence for a specified analytical or development use.", "Compare VEGF isoform binding and inhibitory potency under compatible assay conditions.", "Flag storage excursions or degradation evidence requiring retesting or quarantine.", "Link a qualified substance lot to a product record while preserving separate product and clinical decisions." ], "agent_conduct": { "may": [ "Describe pegaptanib and its role in the history of eye treatment from medicines information.", "Report its current authorization status, which has lapsed in some markets." ], "must_not": [ "Recommend it or any eye injection for a specific person.", "Present it as a current first-line treatment where it is no longer authorized.", "Supply it outside the regulated medicines chain." ], "requires_human": [ "Any decision to treat a patient's eye condition." ] }, "ethics": { "considerations": [ "Eye injections carry risks of infection and vision loss and need specialist care.", "Outdated treatment information can lead patients away from better options." ], "affected_parties": [ "Patients with macular disease", "Eye specialists" ] }, "owners": { "steward": "The marketing authorization holder; medicines regulators decide its status.", "master_systems": [ "Medicines regulators' product registers" ] }, "visual_identification": [ "Supplied as a solution in a prefilled syringe for injection into the eye." ], "failure_modes_and_hazards": [ "Injection into the eye can cause infection, raised pressure or retinal damage." ], "what_it_is_for": [ "Pegaptanib was developed for specialist ophthalmic treatment of neovascular age-related macular degeneration through inhibition of VEGF165.", "It is also encountered in pharmaceutical analysis and research on modified RNA aptamers and targeted inhibition of blood vessel growth." ], "standards_and_regulation": [ "The Anatomical Therapeutic Chemical classification, maintained by the WHO Collaborating Centre for Drug Statistics Methodology, assigns pegaptanib code S01LA03 among ocular antineovascularisation agents." ] }, "sources": [ { "id": "wikidata", "title": "Wikidata item Q409935: pegaptanib", "url": "https://www.wikidata.org/wiki/Q409935", "url_status": "live", "what_it_supports": "identity and sense of the item", "checked_by": "wikidata-api" }, { "id": "wikipedia-en", "title": "Wikipedia: Pegaptanib", "url": "https://en.wikipedia.org/wiki/Pegaptanib", "url_status": "live", "what_it_supports": "general description of the item", "checked_by": "wikidata-api sitelink" } ], "structure": { "bundles": [ { "id": "aptamer-conjugate-identity", "name": "Aptamer conjugate identity", "description": "Establish the molecular features that make a material pegaptanib.", "rationale": "Neither an RNA sequence nor a PEG label alone identifies the complete modified conjugate.", "layers": [ { "id": "modified-oligonucleotide", "name": "Modified oligonucleotide", "description": "Resolve the nucleotide chain and its position-specific chemistry.", "findings": [ { "id": "sequence-and-terminal-match", "name": "Sequence and terminal match", "description": "Record evidence for the sequence, nucleotide modifications and terminal structures against a named reference.", "questions": [ { "text": "What exact sequence, position-specific sugar modifications and terminal linkages define the reference pegaptanib oligonucleotide?", "kind": "definition", "id": "sequence-and-terminal-match-q01" }, { "text": "Which analytical results distinguish the sample from truncations, sequence variants and incorrectly modified chains?", "kind": "measurement", "id": "sequence-and-terminal-match-q02" } ] } ] }, { "id": "peg-and-salt-form", "name": "PEG and salt form", "description": "Identify conjugation architecture and the chemical form represented by the sample.", "findings": [ { "id": "complete-conjugate-representation", "name": "Complete conjugate representation", "description": "Connect PEG attachment and distribution to an explicitly identified active-moiety or salt representation.", "questions": [ { "text": "What PEG architecture, attachment chemistry and molar-mass distribution are required by the reference identity?", "kind": "definition", "id": "complete-conjugate-representation-q01" }, { "text": "Does each identifier and reported molecular mass refer to pegaptanib, pegaptanib sodium or an incompletely specified conjugate?", "kind": "boundary", "id": "complete-conjugate-representation-q02" } ] } ] } ] }, { "id": "vegf-recognition-and-potency", "name": "VEGF recognition and potency", "description": "Describe target recognition separately from measured inhibition.", "rationale": "Pegaptanib identity and usability depend on a specific aptamer interaction, while potency depends on the assay context.", "layers": [ { "id": "isoform-recognition", "name": "Isoform recognition", "description": "Resolve which VEGF forms bind and what evidence supports selectivity.", "findings": [ { "id": "target-binding-specificity", "name": "Target-binding specificity", "description": "Record isoform-resolved affinity and evidence about the binding region without assuming all VEGF forms behave alike.", "questions": [ { "text": "Which VEGF isoforms and constructs were tested, and what affinity or non-binding limits were measured for each?", "kind": "measurement", "id": "target-binding-specificity-q01" }, { "text": "What experimental evidence connects recognition to the VEGF165 heparin-binding domain?", "kind": "provenance", "id": "target-binding-specificity-q02" } ] } ] }, { "id": "functional-activity", "name": "Functional activity", "description": "Connect molecular binding to inhibition in a defined experimental system.", "findings": [ { "id": "assay-qualified-potency", "name": "Assay-qualified potency", "description": "Interpret activity using an identified reference, endpoint and solution conditions.", "questions": [ { "text": "What receptor-binding or cellular endpoint demonstrates inhibition, and how is potency normalized to the reference material?", "kind": "measurement", "id": "assay-qualified-potency-q01" }, { "text": "Which differences in buffer, ions, target concentration or incubation prevent two potency results from being compared directly?", "kind": "boundary", "id": "assay-qualified-potency-q02" } ] } ] } ] }, { "id": "lot-composition-and-quality", "name": "Lot composition and quality", "description": "Determine how much intact pegaptanib a sample contains and what accompanies it.", "rationale": "Total oligonucleotide or bulk mass can conceal impurities and incomplete conjugation.", "layers": [ { "id": "content-and-presentation", "name": "Content and presentation", "description": "Specify material form and the basis of quantitative measurements.", "findings": [ { "id": "qualified-content-result", "name": "Qualified content result", "description": "Record content with chemical basis, method and uncertainty appropriate to the sample presentation.", "questions": [ { "text": "Is reported content based on intact pegaptanib, sodium salt, total oligonucleotide or total dry material?", "kind": "definition", "id": "qualified-content-result-q01" }, { "text": "What method measures concentration or mass fraction, and how are solvent, water and counterions accounted for?", "kind": "measurement", "id": "qualified-content-result-q02" } ] } ] }, { "id": "impurities-and-release", "name": "Impurities and release", "description": "Evaluate related substances and contaminants against a documented intended use.", "findings": [ { "id": "use-specific-quality-evidence", "name": "Use-specific quality evidence", "description": "Separate analytical purity from the wider evidence required to qualify a drug-substance lot.", "questions": [ { "text": "Which methods resolve free PEG, unconjugated aptamer, sequence-related impurities and degradation products, and at what reporting limits?", "kind": "measurement", "id": "use-specific-quality-evidence-q01" }, { "text": "Which impurity, residual-reagent and microbial or endotoxin requirements apply to this lot's intended use, and what results support release?", "kind": "action", "id": "use-specific-quality-evidence-q02" } ] } ] } ] }, { "id": "stability-and-material-handling", "name": "Stability and material handling", "description": "Track conditions that preserve or compromise the pegaptanib conjugate and its measured activity.", "rationale": "Structural integrity, solution behavior and functional activity need evidence tied to the specific presentation.", "layers": [ { "id": "integrity-over-time", "name": "Integrity over time", "description": "Relate exposure history to chemical and functional change.", "findings": [ { "id": "stability-indicating-evidence", "name": "Stability-indicating evidence", "description": "Assess storage claims through methods capable of detecting relevant conjugate changes.", "questions": [ { "text": "Which observed changes in oligonucleotide integrity, PEG attachment or potency limit stability under the tested conditions?", "kind": "measurement", "id": "stability-indicating-evidence-q01" }, { "text": "What studies support storage duration and excursion limits for this exact substance presentation and container?", "kind": "provenance", "id": "stability-indicating-evidence-q02" } ] } ] }, { "id": "solution-and-contact-conditions", "name": "Solution and contact conditions", "description": "Determine whether preparation and material contact preserve recoverable, active pegaptanib.", "findings": [ { "id": "handling-compatibility", "name": "Handling compatibility", "description": "Record validated preparation conditions and evidence for losses or changes during handling.", "questions": [ { "text": "How do pH, ionic composition, concentration and container or filter contact affect recovery and measured activity?", "kind": "measurement", "id": "handling-compatibility-q01" }, { "text": "After dilution, transfer or a temperature excursion, what evidence permits continued use and what triggers retesting or quarantine?", "kind": "action", "id": "handling-compatibility-q02" } ] } ] } ] }, { "id": "substance-product-and-use-boundaries", "name": "Substance, product and use boundaries", "description": "Connect pegaptanib to authoritative records without transferring product permissions or instructions to arbitrary material.", "rationale": "A therapeutic ingredient's name does not establish sample grade, finished-product status or permitted use.", "layers": [ { "id": "record-and-product-linkage", "name": "Record and product linkage", "description": "Maintain traceable relationships between the registry thing, chemical forms and medicinal products.", "findings": [ { "id": "authoritative-identity-links", "name": "Authoritative identity links", "description": "Verify identifiers and product relationships with jurisdiction and date attached.", "questions": [ { "text": "Which authoritative records resolve pegaptanib and its sodium salt, and do their structural representations agree?", "kind": "provenance", "id": "authoritative-identity-links-q01" }, { "text": "Which statements concern the substance itself, and which concern a particular Macugen formulation, authorization or historical label?", "kind": "boundary", "id": "authoritative-identity-links-q02" } ] } ] }, { "id": "handling-and-use-qualification", "name": "Handling and use qualification", "description": "Determine what handling and downstream uses the material's documented status supports.", "findings": [ { "id": "evidence-bounded-disposition", "name": "Evidence-bounded disposition", "description": "Use applicable material safety information and qualification evidence to support a disposition decision.", "questions": [ { "text": "What supplier safety data and jurisdiction-specific hazard classifications apply to this chemical form and concentration, and are exposure limits established?", "kind": "provenance", "id": "evidence-bounded-disposition-q01" }, { "text": "Does the lot documentation support reference-standard use, research use or transfer into a qualified pharmaceutical process?", "kind": "action", "id": "evidence-bounded-disposition-q02" } ] } ] } ] }, { "id": "evidence-and-external-alignment", "name": "Evidence and external alignment", "description": "What the world already says about this thing, gathered so the model can be checked against it.", "rationale": "A model that cannot be lined up against existing standards, identifiers and practice cannot be adopted by anyone who already uses them.", "layers": [ { "id": "reported-evidence", "name": "Reported evidence", "description": "Findings from the breadth pass, kept separate from the structural claims.", "findings": [ { "id": "evidence-confidence-notes", "name": "Check these first", "description": "Recalled without web access and unsourced; every item is a lead to verify.", "evidence": [ "This description is recalled knowledge; no sources were consulted.", "Current marketing availability, authorization status and approved indications require jurisdiction-specific verification.", "Exact molecular mass, chemical identifiers and analytical specifications should be checked for the relevant salt and polyethylene glycol composition." ], "questions": [ { "id": "evidence-confidence-notes-q01", "text": "Which of these check these first hold for the sense of pegaptanib this model covers, and on what evidence?", "kind": "provenance" } ] }, { "id": "evidence-identifiers", "name": "Identifiers and schemes", "description": "Recalled without web access and unsourced; every item is a lead to verify.", "evidence": [ { "scheme": "International Nonproprietary Name (INN)", "value_or_pattern": "pegaptanib", "note": "Names the active substance; pegaptanib sodium is its pharmaceutical salt form." }, { "scheme": "WHO Anatomical Therapeutic Chemical (ATC) classification", "value_or_pattern": "S01LA03", "note": "Classification under ophthalmic antineovascularisation agents." } ], "questions": [ { "id": "evidence-identifiers-q01", "text": "Which of these identifiers and schemes hold for the sense of pegaptanib this model covers, and on what evidence?", "kind": "provenance" } ] }, { "id": "evidence-real-world-use", "name": "Real-world use", "description": "Recalled without web access and unsourced; every item is a lead to verify.", "evidence": [ "Used as the active ingredient in Macugen, an intravitreal medicine for neovascular (wet) age-related macular degeneration.", "An established example of an aptamer used as a therapeutic drug." ], "questions": [ { "id": "evidence-real-world-use-q01", "text": "Which of these real-world use hold for the sense of pegaptanib this model covers, and on what evidence?", "kind": "provenance" } ] }, { "id": "evidence-measurements", "name": "Typical measurements", "description": "Recalled without web access and unsourced; every item is a lead to verify.", "evidence": [ { "quantity": "RNA aptamer length", "typical_range": "28", "unit": "nucleotides" }, { "quantity": "Approximate molecular mass of the pegylated molecule", "typical_range": "50", "unit": "kDa" } ], "questions": [ { "id": "evidence-measurements-q01", "text": "Which of these typical measurements hold for the sense of pegaptanib this model covers, and on what evidence?", "kind": "provenance" } ] }, { "id": "evidence-failure-modes-and-hazards", "name": "Failure modes and hazards", "description": "Recalled without web access and unsourced; every item is a lead to verify.", "evidence": [ "Intravitreal administration carries a risk of endophthalmitis.", "Injection-associated complications include retinal detachment and traumatic cataract.", "Intraocular pressure can increase after injection.", "Hypersensitivity reactions can occur.", "Oligonucleotide degradation or loss of the aptamer's binding conformation can impair biological activity." ], "questions": [ { "id": "evidence-failure-modes-and-hazards-q01", "text": "Which of these failure modes and hazards hold for the sense of pegaptanib this model covers, and on what evidence?", "kind": "provenance" } ] }, { "id": "evidence-neighbours", "name": "Neighbouring kinds and how to tell them apart", "description": "Recalled without web access and unsourced; every item is a lead to verify.", "evidence": [ { "name": "pegaptanib sodium", "difference": "The sodium salt form of pegaptanib, rather than a different therapeutic aptamer." }, { "name": "Macugen", "difference": "A branded formulated medicinal product containing pegaptanib sodium, rather than the active substance itself." }, { "name": "ranibizumab", "difference": "An antibody fragment targeting VEGF-A, whereas pegaptanib is an RNA aptamer with selectivity for VEGF165." }, { "name": "aflibercept", "difference": "A recombinant fusion protein that acts as a soluble ligand trap, whereas pegaptanib is an oligonucleotide aptamer." } ], "questions": [ { "id": "evidence-neighbours-q01", "text": "Which of these neighbouring kinds and how to tell them apart hold for the sense of pegaptanib this model covers, and on what evidence?", "kind": "provenance" } ] } ] } ] } ] }, "openQuestions": [ "Which authoritative structural reference resolves nucleotide counting, terminal residues, PEG architecture and identifier mappings for pegaptanib versus pegaptanib sodium?", "Which publicly accessible specifications define acceptable conjugation distribution, related substances and validated potency limits for qualified pegaptanib drug substance?", "What stability and handling limits are established for bulk pegaptanib independently of finished Macugen formulations?", "Which material-specific GHS classifications, exposure limits and physical-property measurements are available, and which properties are inapplicable or obscured by decomposition and polymer distribution?", "Which jurisdictions currently maintain relevant product authorizations or supply, and how should those dated product facts be linked without becoming intrinsic substance properties?" ], "statistics": { "bundles": 6, "layers": 11, "findings": 16, "questions": 26 } }