<?xml version="1.0" encoding="UTF-8"?>

  <!-- Example: Trastuzumab (humanised monoclonal antibody against HER2).
     Demonstrates the new SubstanceDefinition protein backbones added for
     FHIR-57660: .protein.subunit (heavy + light chains), disulfide linkages,
     N/C-terminal modifications, .protein.gene with humanised mouse origin,
     and .relationship typed as TherapeuticTarget (HER2). -->
<SubstanceDefinition xmlns="http://hl7.org/fhir">
  <id value="trastuzumab"/>
  <identifier>
    <system value="http://example.europa.eu/fhir/SMSId"/>
    <value value="TRAS9123H"/>
  </identifier>
  <status>
    <coding>
      <system value="http://hl7.org/fhir/publication-status"/>
      <code value="active"/>
      <display value="Active"/>
    </coding>
  </status>
  <classification>
    <coding>
      <system value="http://example.europa.eu/fhir/SubstanceType"/>
      <code value="protein"/>
      <display value="Protein"/>
    </coding>
  </classification>
  <domain>
    <coding>
      <system value="http://example.europa.eu/fhir/Domain"/>
      <code value="human"/>
      <display value="Human use"/>
    </coding>
  </domain>
  <description value="Trastuzumab — humanised IgG1 monoclonal antibody targeting the human epidermal growth factor receptor 2 (HER2/ErbB2). Variable regions derived from murine antibody 4D5, grafted onto human IgG1 framework. Produced in Chinese hamster ovary (CHO) cells."/>
  <code>
    <code>
      <coding>
        <system value="http://example.europa.eu/fhir/Substance"/>
        <code value="TRAS9123H"/>
      </coding>
    </code>
  </code>
  <name>
    <name value="Trastuzumab"/>
    <preferred value="true"/>
    <language>
      <coding>
        <system value="urn:ietf:bcp:47"/>
        <code value="en"/>
        <display value="English"/>
      </coding>
    </language>
    <official>
      <authority>
        <coding>
          <system value="http://hl7.org/fhir/substance-name-authority"/>
          <code value="INN"/>
          <display value="INN"/>
        </coding>
      </authority>
      <status>
        <coding>
          <system value="http://hl7.org/fhir/publication-status"/>
          <code value="active"/>
          <display value="Active"/>
        </coding>
      </status>
    </official>
  </name>
  <name>
    <name value="Herceptin"/>
    <preferred value="false"/>
  </name>
  <protein>
    <sequenceType>
      <coding>
        <system value="http://hl7.org/fhir/substance-sequence-type"/>
        <code value="complete"/>
        <display value="Complete"/>
      </coding>
    </sequenceType>
    <numberOfSubunits value="2"/>
    <disulfideLinkage value="HC22-HC96; HC144-HC200; HC222-LC214; HC228-HC228'; HC231-HC231'; HC265-HC325; HC371-HC429"/>
    <subunit>
      <subunit value="1"/>
      <sequence value="EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSS..."/>
      <length value="450"/>
      <nTerminalModification>
        <concept>
          <coding>
            <system value="http://example.europa.eu/fhir/Modification"/>
            <code value="pyroglutamate"/>
            <display value="Pyroglutamic acid (pE)"/>
          </coding>
        </concept>
      </nTerminalModification>
      <cTerminalModification>
        <concept>
          <coding>
            <system value="http://example.europa.eu/fhir/Modification"/>
            <code value="lysine-clipped"/>
            <display value="C-terminal lysine clipping"/>
          </coding>
        </concept>
      </cTerminalModification>
    </subunit>
    <subunit>
      <subunit value="2"/>
      <sequence value="DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIK..."/>
      <length value="214"/>
    </subunit>
    <gene>
      <sequenceOrigin>
        <coding>
          <system value="http://hl7.org/fhir/gene-sequence-origin"/>
          <code value="humanised-mouse"/>
          <display value="Humanised mouse"/>
        </coding>
      </sequenceOrigin>
      <gene>
        <concept>
          <coding>
            <system value="http://www.genenames.org"/>
            <code value="IGHG1"/>
            <display value="Immunoglobulin heavy constant gamma 1"/>
          </coding>
        </concept>
      </gene>
    </gene>
  </protein>
  <relationship>
    <substanceDefinitionReference>
      <reference value="SubstanceDefinition/her2"/>
      <display value="Receptor tyrosine-protein kinase erbB-2 (HER2)"/>
    </substanceDefinitionReference>
    <type>
      <coding>
        <system value="http://hl7.org/fhir/substance-relationship-type"/>
        <code value="TherapeuticTarget"/>
        <display value="Therapeutic target"/>
      </coding>
    </type>
    <interaction>
      <coding>
        <system value="http://hl7.org/fhir/substance-interaction-type"/>
        <code value="binding"/>
        <display value="Binding"/>
      </coding>
    </interaction>
    <measurementType>
      <coding>
        <system value="http://hl7.org/fhir/substance-measurement-type"/>
        <code value="kd"/>
        <display value="Kd"/>
      </coding>
    </measurementType>
    <amountQuantity>
      <value value="0.1"/>
      <unit value="nM"/>
      <system value="http://unitsofmeasure.org"/>
      <code value="nmol/L"/>
    </amountQuantity>
  </relationship>
</SubstanceDefinition>