Difference between revisions of "Team:Sydney Australia/Patent Law"

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 +
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 +
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<div class="row">
 
<div class="row">
 
         <select>
 
         <select>
−
             <option value="choose">Choose Patent</option>
+
             <option value="choose">Choose a patent</option>
−
             <option value="1">Dimarchi</option>
+
             <option value="1">Lee et al. 2003</option>
−
             <option value="2">2nd patent</option>
+
             <option value="2">Lee et al. 2004</option>
−
             <option value="3">3rd patent</option>
+
             <option value="3">Kjeldsen et al. 2004</option>
 +
            <option value="4">Weiss et al. 2009</option>
 +
            <option value="5">Stowell et al. 2012</option>
 
         </select>
 
         </select>
 
     </div>
 
     </div>
−
     <div class="choose box">DI MARCHI
+
     <div class="choose box">
 +
    <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
<p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
<p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
  
 +
    <h4>GENERAL PATENT STUFF</h4>
 
<p class="MsoNormal" align="center" style="text-align:center"><b style="mso-bidi-font-weight:
 
<p class="MsoNormal" align="center" style="text-align:center"><b style="mso-bidi-font-weight:
 
normal"><span lang="EN-AU" style="font-size:20.0pt;font-family:Quicksand">DIMARCHI
 
normal"><span lang="EN-AU" style="font-size:20.0pt;font-family:Quicksand">DIMARCHI
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</div>
 
</div>
 
<div class="patent_1 box">
 
<div class="patent_1 box">
−
<table width="709">
+
<p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
−
<tbody>
+
<p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
−
<tr>
+
<p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
−
<td width="354">
+
 
−
<p><strong>Claims</strong></p>
+
<p class="MsoNormal" align="center" style="text-align:center"><b style="mso-bidi-font-weight:
−
</td>
+
normal"><span lang="EN-AU" style="font-size:20.0pt;font-family:Quicksand">LEE ET
−
<td width="302">
+
AL.<o:p></o:p></span></b></p>
−
<p><strong>Comparison with our sequence</strong></p>
+
 
−
</td>
+
<p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:16.0pt;font-family:Quicksand">Single Chain Insulin Analog and
−
<td width="52">
+
a polynucleotide sequence encoding the <span class="SpellE">analog</span><o:p></o:p></span></p>
−
<p><strong>Y/N</strong></p>
+
 
−
</td>
+
<p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:16.0pt;font-family:Quicksand">Patent No: <b style="mso-bidi-font-weight:
−
</tr>
+
normal">US 6,630,348 B1<o:p></o:p></b></span></p>
−
<tr>
+
 
−
<td width="354">
+
<p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:16.0pt;font-family:Quicksand">October <span class="GramE">7<sup>th</sup></span>
−
<p>&nbsp; A single chain insulin agonist analogue with stricture of B-LM-A wherein&nbsp;B represents an insulin B chain comprising the sequence R<sub>22</sub>X<sub>25</sub>LCGX<sub>29&hellip;</sub> <sub>&nbsp;</sub>and A represents an insulin A chain comprising the sequence GIVX<sub>4</sub>X<sub>5</sub>CCX<sub>8&hellip;</sub>-R<sub>13</sub> </p>
+
2003<o:p></o:p></span></p>
−
</td>
+
 
−
<td width="302">
+
<p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
−
<p>Both insulin A and B chains involve R groups which stand for modifications eg. carboxylation. As our insulin B chain does not contain any modifications (except an additional glycine at the A chain), our construct is outside the patent</p>
+
 
−
</td>
+
<table class="MsoTableGrid" border="1" cellspacing="0" cellpadding="0" width="100%" style="width:100.0%;border-collapse:collapse;border:none;mso-border-alt:solid windowtext .5pt;
−
<td width="52">
+
mso-yfti-tbllook:1184;mso-padding-alt:0cm 5.4pt 0cm 5.4pt">
−
<p>N</p>
+
<tbody><tr style="mso-yfti-irow:0;mso-yfti-firstrow:yes;height:53.95pt">
−
</td>
+
  <td width="50%" style="width:50.6%;border:solid windowtext 1.0pt;mso-border-alt:
−
</tr>
+
  solid windowtext .5pt;background:#A1C4C8;padding:0cm 5.4pt 0cm 5.4pt;
−
<tr>
+
  height:53.95pt">
−
<td width="354">
+
  <p class="MsoNormal" align="center" style="text-align:center"><b style="mso-bidi-font-weight:normal"><span lang="EN-AU" style="font-size:15.0pt;
−
<p>Furthermore the linking moiety linking the carboxy terminus of the B chain to the amino terminus of the A chain; further wherein the linking moiety is an 8 amino acid sequence comprising of the sequence X<sub>51</sub>X<sub>52</sub>GSSSX<sub>57</sub>X<sub>58</sub> wherein</p>
+
  font-family:Quicksand"><o:p>&nbsp;</o:p></span></b></p>
−
<p>X<sub>51</sub> = group consisting of glycine, alanine, valine, leucine, isoleucine, isoleucine and ornithine <br /> <br /> X<sub>52</sub> = any amino acid other than tyrosine<br /> <br /> X<sub>57</sub> and X<sub>58</sub> are independently selected form the ground consisting of arginine, lysine and ornithine</p>
+
  <p class="MsoNormal" align="center" style="text-align:center"><b style="mso-bidi-font-weight:normal"><span lang="EN-AU" style="font-size:15.0pt;
−
</td>
+
  font-family:Quicksand">CLAIM<br style="mso-special-character:line-break">
−
<td width="302">
+
  <!--[if !supportLineBreakNewLine]--><br style="mso-special-character:line-break">
−
<p><em>Our amino acid sequence is squarely outside the scope of 8 amino acids.</em></p>
+
  <!--[endif]--><o:p></o:p></span></b></p>
−
<p>&nbsp;</p>
+
  </td>
−
<p>Even if we did fall within the claim; we do not contain the 8 amino acid sequence using both potential orientations</p>
+
  <td width="43%" style="width:43.1%;border:solid windowtext 1.0pt;border-left:
−
<p>X<sub>51</sub> is glutamine or arganine in our sequence</p>
+
  none;mso-border-left-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
−
<p>&nbsp;&nbsp; B-chain - QR&hellip;..RR &ndash; A-chain</p>
+
  background:#A1C4C8;padding:0cm 5.4pt 0cm 5.4pt;height:53.95pt">
−
</td>
+
  <p class="MsoNormal" align="center" style="text-align:center"><b style="mso-bidi-font-weight:normal"><span lang="EN-AU" style="font-size:15.0pt;
−
<td width="52">
+
  font-family:Quicksand"><br>
−
<p>N</p>
+
  COMPARISON WITH OUR SEQUENCE<br style="mso-special-character:line-break">
−
</td>
+
  <!--[if !supportLineBreakNewLine]--><br style="mso-special-character:line-break">
−
</tr>
+
  <!--[endif]--><o:p></o:p></span></b></p>
−
<tr>
+
  </td>
−
<td width="354">
+
  <td width="6%" style="width:6.3%;border:solid windowtext 1.0pt;border-left:
−
<p>The LM also requires the sequence of GAGSSSRR or a sequence that differs from GAGSSRR by 1 or 2 amino acids</p>
+
  none;mso-border-left-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
−
</td>
+
  background:#A1C4C8;padding:0cm 5.4pt 0cm 5.4pt;height:53.95pt">
−
<td width="302">
+
  <p class="MsoNormal" align="center" style="text-align:center"><b style="mso-bidi-font-weight:normal"><span lang="EN-AU" style="font-size:15.0pt;
−
<p>Our sequence is 12 amino acids long and differs by more than 4 amino acids.</p>
+
  font-family:Quicksand">Y/N<o:p></o:p></span></b></p>
−
</td>
+
  </td>
−
<td width="52">
+
</tr>
−
<p>N</p>
+
<tr style="mso-yfti-irow:1">
−
</td>
+
  <td width="50%" style="width:50.6%;border:solid windowtext 1.0pt;border-top:
−
</tr>
+
  none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
−
<tr>
+
  padding:0cm 5.4pt 0cm 5.4pt">
−
<td width="354">
+
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
−
<p>LM represents linking moiety linking the carboxyl terminus of the B chain to the amino terminus of the a chain, wherein said linking moiety is an 8 amino acid sequence consisting of X<sub>51</sub>X<sub>52</sub>X<sub>53</sub>X<sub>54</sub>&hellip; wherein &nbsp;X<sub>51</sub>&nbsp;is selected from the group consisting of glycine, alanine, valine, leucine, isoleucine and proline&hellip;</p>
+
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">A single chain insulin analogue
−
</td>
+
  compound of formula (I) having the properties of greater insulin receptor
−
<td width="302">
+
  binding activity than proinsulin and less insulin receptor binding activity
−
<p>&nbsp;Similarly, the patent claim is over a 8 amino acid sequence. Applying the same principle our<br /> </p>
+
  than insulin:<br style="mso-special-character:line-break">
−
<p>X<sub>51</sub> is glutamine or arginine (depending on orientation) and outside the scope&nbsp;</p>
+
  <!--[if !supportLineBreakNewLine]--><br style="mso-special-character:line-break">
−
</td>
+
  <!--[endif]--><o:p></o:p></span></p>
−
<td width="52">
+
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><br>B chain -<span style="mso-spacerun:yes">&nbsp; </span>X </span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-fareast-font-family:Helvetica;
−
<p>N</p>
+
  mso-bidi-font-family:Helvetica">–</span><span lang="EN-AU" style="font-size:
−
</td>
+
  14.0pt;font-family:Quicksand"> A chain wherein:</span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-fareast-font-family:Helvetica;
−
</tr>
+
  mso-bidi-font-family:Helvetica"><o:p></o:p></span></p>
−
</tbody>
+
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-fareast-font-family:Helvetica;
−
</table>
+
  mso-bidi-font-family:Helvetica"><o:p>&nbsp;</o:p></span></p>
−
</div>
+
  </td>
−
+
  <td width="43%" style="width:43.1%;border-top:none;border-left:none;
−
+
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
−
    <div class="patent_2 box">2nd patent shit</div>
+
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
−
    <div class="patent_3 box">3rd patent shite</div>
+
  mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">General B </span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-fareast-font-family:
 +
  Helvetica;mso-bidi-font-family:Helvetica">–</span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"> X </span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-fareast-font-family:Helvetica;
 +
  mso-bidi-font-family:Helvetica">–</span><span lang="EN-AU" style="font-size:
 +
  14.0pt;font-family:Quicksand"> A chain single chain formula</span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-fareast-font-family:
 +
  Helvetica;mso-bidi-font-family:Helvetica"><o:p></o:p></span></p>
 +
  </td>
 +
  <td width="6%" style="width:6.3%;border-top:none;border-left:none;border-bottom:
 +
  solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;mso-border-top-alt:
 +
  solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;mso-border-alt:
 +
  solid windowtext .5pt;background:#E2EFD9;mso-background-themecolor:accent6;
 +
  mso-background-themetint:51;padding:0cm 5.4pt 0cm 5.4pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">Y<o:p></o:p></span></p>
 +
  </td>
 +
</tr>
 +
<tr style="mso-yfti-irow:2">
 +
  <td width="50%" style="width:50.6%;border:solid windowtext 1.0pt;border-top:
 +
  none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
 +
  padding:0cm 5.4pt 0cm 5.4pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">B and A chain are human
 +
  insulin chains, respectively and,<o:p></o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  </td>
 +
  <td width="43%" style="width:43.1%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">Our B and A chain are human
 +
  insulin chains although our A chain includes a modification (additional
 +
  glycine)<o:p></o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  </td>
 +
  <td width="6%" style="width:6.3%;border-top:none;border-left:none;border-bottom:
 +
  solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;mso-border-top-alt:
 +
  solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;mso-border-alt:
 +
  solid windowtext .5pt;background:#FFC8CD;padding:0cm 5.4pt 0cm 5.4pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">N<o:p></o:p></span></p>
 +
  </td>
 +
</tr>
 +
<tr style="mso-yfti-irow:3;mso-yfti-lastrow:yes;height:79.2pt">
 +
  <td width="50%" style="width:50.6%;border:solid windowtext 1.0pt;border-top:
 +
  none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
 +
  padding:0cm 5.4pt 0cm 5.4pt;height:79.2pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">X is a joining peptide of
 +
  about 5 to 18 amino acids comprising the following sequence: <span class="SpellE">Gly</span>-<span class="SpellE">Gly</span>-<span class="SpellE">Gly</span>-Pro-<span class="SpellE">Gly</span>- Lys-<span class="SpellE">Arg</span><o:p></o:p></span></p>
 +
  </td>
 +
  <td width="43%" style="width:43.1%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt;height:79.2pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">Where the term </span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-fareast-font-family:
 +
  Helvetica;mso-bidi-font-family:Helvetica">‘</span><i style="mso-bidi-font-style:
 +
  normal"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">comprising</span></i><i style="mso-bidi-font-style:normal"><span lang="EN-AU" style="font-size:14.0pt;
 +
  font-family:Helvetica;mso-fareast-font-family:Helvetica;mso-bidi-font-family:
 +
  Helvetica">’ </span></i><span lang="EN-AU" style="font-size:14.0pt;font-family:
 +
  Quicksand">is included, the patent requires</span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-fareast-font-family:Helvetica;
 +
  mso-bidi-font-family:Helvetica"> </span><span lang="EN-AU" style="font-size:
 +
  14.0pt;font-family:Quicksand">that the specific sequence named MUST be part
 +
  of the linker region.<i style="mso-bidi-font-style:normal"><o:p></o:p></i></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">Although our sequence is 12
 +
  amino acids long, it does not contain the </span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-fareast-font-family:Helvetica;
 +
  mso-bidi-font-family:Helvetica">‘</span><span lang="EN-AU" style="font-size:
 +
  14.0pt;font-family:Quicksand">GGGPGLR</span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-fareast-font-family:Helvetica;
 +
  mso-bidi-font-family:Helvetica">’</span><span lang="EN-AU" style="font-size:
 +
  14.0pt;font-family:Quicksand"> identified in the patent</span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-fareast-font-family:
 +
  Helvetica;mso-bidi-font-family:Helvetica"><o:p></o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-fareast-font-family:Helvetica;
 +
  mso-bidi-font-family:Helvetica"><o:p>&nbsp;</o:p></span></p>
 +
  </td>
 +
  <td width="6%" style="width:6.3%;border-top:none;border-left:none;border-bottom:
 +
  solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;mso-border-top-alt:
 +
  solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;mso-border-alt:
 +
  solid windowtext .5pt;background:#FFC8CD;padding:0cm 5.4pt 0cm 5.4pt;
 +
  height:79.2pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">N<o:p></o:p></span></p>
 +
  </td>
 +
</tr>
 +
</tbody></table></div>
 +
    <div class="patent_2 box">
 +
<p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
<p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
<p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
 
 +
<p class="MsoNormal" align="center" style="text-align:center"><b style="mso-bidi-font-weight:
 +
normal"><span lang="EN-AU" style="font-size:20.0pt;font-family:Quicksand">LEE ET
 +
AL.<o:p></o:p></span></b></p>
 +
 
 +
<p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:16.0pt;font-family:Quicksand">Single Chain Insulin <span class="SpellE">Analogs</span><o:p></o:p></span></p>
 +
 
 +
<p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:16.0pt;font-family:Quicksand">Patent No: <b style="mso-bidi-font-weight:
 +
normal">EP 1 193 272 B1<o:p></o:p></b></span></p>
 +
 
 +
<p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:16.0pt;font-family:Quicksand">October <span class="GramE">30<sup>th</sup></span>
 +
2004<o:p></o:p></span></p>
 +
 
 +
<p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
 
 +
<table class="MsoTableGrid" border="1" cellspacing="0" cellpadding="0" width="100%" style="width:100.0%;border-collapse:collapse;border:none;mso-border-alt:solid windowtext .5pt;
 +
mso-yfti-tbllook:1184;mso-padding-alt:0cm 5.4pt 0cm 5.4pt">
 +
<tbody><tr style="mso-yfti-irow:0;mso-yfti-firstrow:yes;height:12.75pt">
 +
  <td width="48%" style="width:48.28%;border:solid windowtext 1.0pt;mso-border-alt:
 +
  solid windowtext .5pt;background:#BBB8EB;padding:0cm 5.4pt 0cm 5.4pt;
 +
  height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><b style="mso-bidi-font-weight:normal"><span lang="EN-AU" style="font-size:15.0pt;
 +
  font-family:Quicksand"><o:p>&nbsp;</o:p></span></b></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><b style="mso-bidi-font-weight:normal"><span lang="EN-AU" style="font-size:15.0pt;
 +
  font-family:Quicksand">CLAIM<br style="mso-special-character:line-break">
 +
  <!--[if !supportLineBreakNewLine]--><br style="mso-special-character:line-break">
 +
  <!--[endif]--><o:p></o:p></span></b></p>
 +
  </td>
 +
  <td width="45%" style="width:45.5%;border:solid windowtext 1.0pt;border-left:
 +
  none;mso-border-left-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
 +
  background:#BBB8EB;padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><b style="mso-bidi-font-weight:normal"><span lang="EN-AU" style="font-size:15.0pt;
 +
  font-family:Quicksand"><br>
 +
  COMPARISON WITH OUR SEQUENCE<br style="mso-special-character:line-break">
 +
  <!--[if !supportLineBreakNewLine]--><br style="mso-special-character:line-break">
 +
  <!--[endif]--><o:p></o:p></span></b></p>
 +
  </td>
 +
  <td width="6%" style="width:6.22%;border:solid windowtext 1.0pt;border-left:
 +
  none;mso-border-left-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
 +
  background:#BBB8EB;padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><b style="mso-bidi-font-weight:normal"><span lang="EN-AU" style="font-size:15.0pt;
 +
  font-family:Quicksand">Y/N<o:p></o:p></span></b></p>
 +
  </td>
 +
</tr>
 +
<tr style="mso-yfti-irow:1;height:12.75pt">
 +
  <td width="48%" style="width:48.28%;border:solid windowtext 1.0pt;border-top:
 +
  none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
 +
  padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">A single chain insulin
 +
  analogue compound of formula (I) having the properties of greater insulin
 +
  receptor binding activity than <span class="SpellE">prosinsulin</span> and less
 +
  insulin receptor binding activity than insulin:<o:p></o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">B Chain </span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-fareast-font-family:
 +
  Helvetica;mso-bidi-font-family:Helvetica">–</span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"> U<sub>I</sub> </span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-fareast-font-family:
 +
  Helvetica;mso-bidi-font-family:Helvetica">–</span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"> Z<sub>n</sub> </span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-fareast-font-family:
 +
  Helvetica;mso-bidi-font-family:Helvetica">–</span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"> Y </span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-fareast-font-family:Helvetica;
 +
  mso-bidi-font-family:Helvetica">–</span><span lang="EN-AU" style="font-size:
 +
  14.0pt;font-family:Quicksand"> Z<sub>I</sub> </span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-fareast-font-family:Helvetica;
 +
  mso-bidi-font-family:Helvetica">–</span><span lang="EN-AU" style="font-size:
 +
  14.0pt;font-family:Quicksand"> U<sub>n </sub></span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-fareast-font-family:Helvetica;
 +
  mso-bidi-font-family:Helvetica">–</span><span lang="EN-AU" style="font-size:
 +
  14.0pt;font-family:Quicksand"> A chain</span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-fareast-font-family:Helvetica;
 +
  mso-bidi-font-family:Helvetica"><o:p></o:p></span></p>
 +
  </td>
 +
  <td width="45%" style="width:45.5%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  </td>
 +
  <td width="6%" style="width:6.22%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;background:#E2EFD9;mso-background-themecolor:
 +
  accent6;mso-background-themetint:51;padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  </td>
 +
</tr>
 +
<tr style="mso-yfti-irow:2;height:14.15pt">
 +
  <td width="48%" style="width:48.28%;border:solid windowtext 1.0pt;border-top:
 +
  none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
 +
  padding:0cm 5.4pt 0cm 5.4pt;height:14.15pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">B and A chain are human
 +
  insulin chains respectively and<o:p></o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  </td>
 +
  <td width="45%" style="width:45.5%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt;height:14.15pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">We have a modified A chain<o:p></o:p></span></p>
 +
  </td>
 +
  <td width="6%" style="width:6.22%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;background:#FFC8CD;padding:0cm 5.4pt 0cm 5.4pt;
 +
  height:14.15pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">N<o:p></o:p></span></p>
 +
  </td>
 +
</tr>
 +
<tr style="mso-yfti-irow:3;height:18.35pt">
 +
  <td width="48%" style="width:48.28%;border:solid windowtext 1.0pt;border-top:
 +
  none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
 +
  padding:0cm 5.4pt 0cm 5.4pt;height:18.35pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">U is an arginine or lysine
 +
  residue<o:p></o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  </td>
 +
  <td width="45%" style="width:45.5%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt;height:18.35pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">Our </span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-fareast-font-family:Helvetica;
 +
  mso-bidi-font-family:Helvetica">‘</span><span lang="EN-AU" style="font-size:
 +
  14.0pt;font-family:Quicksand">U</span><span lang="EN-AU" style="font-size:14.0pt;
 +
  font-family:Quicksand;mso-fareast-font-family:Helvetica;mso-bidi-font-family:
 +
  Helvetica">’</span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">
 +
  is glutamine<o:p></o:p></span></p>
 +
  </td>
 +
  <td width="6%" style="width:6.22%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;background:#FFC8CD;padding:0cm 5.4pt 0cm 5.4pt;
 +
  height:18.35pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">N<o:p></o:p></span></p>
 +
  </td>
 +
</tr>
 +
<tr style="mso-yfti-irow:4;height:27.45pt">
 +
  <td width="48%" style="width:48.28%;border:solid windowtext 1.0pt;border-top:
 +
  none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
 +
  padding:0cm 5.4pt 0cm 5.4pt;height:27.45pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">Z is a glycine<o:p></o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  </td>
 +
  <td width="45%" style="width:45.5%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt;height:27.45pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">Z Is Glycine<o:p></o:p></span></p>
 +
  </td>
 +
  <td width="6%" style="width:6.22%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;background:#E2EFD9;mso-background-themecolor:
 +
  accent6;mso-background-themetint:51;padding:0cm 5.4pt 0cm 5.4pt;height:27.45pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">Y<o:p></o:p></span></p>
 +
  </td>
 +
</tr>
 +
<tr style="mso-yfti-irow:5;height:12.75pt">
 +
  <td width="48%" style="width:48.28%;border:solid windowtext 1.0pt;border-top:
 +
  none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
 +
  padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">I <span class="GramE">is</span>
 +
  an integer of 2 </span><span lang="EN-AU" style="font-size:14.0pt;font-family:
 +
  Quicksand;mso-fareast-font-family:Helvetica;mso-bidi-font-family:Helvetica">–
 +
  n<o:p></o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">N is an integer of 0 or 2 and<o:p></o:p></span></p>
 +
  </td>
 +
  <td width="45%" style="width:45.5%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">The maximum size of the linker
 +
  sequence when considering this is 9 amino acids. Since our sequence is 12
 +
  amino acids they are outside the scope<o:p></o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  </td>
 +
  <td width="6%" style="width:6.22%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;background:#FFC8CD;padding:0cm 5.4pt 0cm 5.4pt;
 +
  height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">N<o:p></o:p></span></p>
 +
  </td>
 +
</tr>
 +
<tr style="mso-yfti-irow:6;mso-yfti-lastrow:yes;height:58.85pt">
 +
  <td width="48%" style="width:48.28%;border:solid windowtext 1.0pt;border-top:
 +
  none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
 +
  padding:0cm 5.4pt 0cm 5.4pt;height:58.85pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">Y is glycine-<b style="mso-bidi-font-weight:normal">proline-</b>glycine, or alanine-<b style="mso-bidi-font-weight:normal">proline</b>-glycine-aspartic acid</span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-fareast-font-family:
 +
  Helvetica;mso-bidi-font-family:Helvetica">–valine, or tyrosine-</span><b style="mso-bidi-font-weight:normal"><span lang="EN-AU" style="font-size:14.0pt;
 +
  font-family:Quicksand">proline</span></b><span lang="EN-AU" style="font-size:
 +
  14.0pt;font-family:Quicksand">-glycine-aspartic acid-valine, or histidine-<b style="mso-bidi-font-weight:normal">proline</b>-glycine-aspartic acid-valine.<o:p></o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  </td>
 +
  <td width="45%" style="width:45.5%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt;height:58.85pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">Our sequence has no proline<o:p></o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  </td>
 +
  <td width="6%" style="width:6.22%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;background:#FFC8CD;padding:0cm 5.4pt 0cm 5.4pt;
 +
  height:58.85pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">N<o:p></o:p></span></p>
 +
  </td>
 +
</tr>
 +
</tbody></table></div>
 +
    <div class="patent_3 box">
 +
    <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
<p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
<p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
 
 +
<p class="MsoNormal" align="center" style="text-align:center"><b style="mso-bidi-font-weight:
 +
normal"><span lang="EN-AU" style="font-size:20.0pt;font-family:Quicksand">KJELDSEN
 +
ET AL.<o:p></o:p></span></b></p>
 +
 
 +
<p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:16.0pt;font-family:Quicksand">Single Chain insulin<o:p></o:p></span></p>
 +
 
 +
<p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:16.0pt;font-family:Quicksand">Patent No:<b style="mso-bidi-font-weight:
 +
normal"> EP 1692168 B1<o:p></o:p></b></span></p>
 +
 
 +
<p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:16.0pt;font-family:Quicksand">December 3<sup>rd</sup>, 2004<o:p></o:p></span></p>
 +
 
 +
<p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
 
 +
<table class="MsoTableGrid" border="1" cellspacing="0" cellpadding="0" width="100%" style="width:100.0%;border-collapse:collapse;border:none;mso-border-alt:solid windowtext .5pt;
 +
mso-yfti-tbllook:1184;mso-padding-alt:0cm 5.4pt 0cm 5.4pt">
 +
<tbody><tr style="mso-yfti-irow:0;mso-yfti-firstrow:yes;height:12.75pt">
 +
  <td width="48%" style="width:48.82%;border:solid windowtext 1.0pt;mso-border-alt:
 +
  solid windowtext .5pt;background:#FFF2CC;mso-background-themecolor:accent4;
 +
  mso-background-themetint:51;padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><b style="mso-bidi-font-weight:normal"><span lang="EN-AU" style="font-size:15.0pt;
 +
  font-family:Quicksand"><o:p>&nbsp;</o:p></span></b></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><b style="mso-bidi-font-weight:normal"><span lang="EN-AU" style="font-size:15.0pt;
 +
  font-family:Quicksand">CLAIM<br style="mso-special-character:line-break">
 +
  <!--[if !supportLineBreakNewLine]--><br style="mso-special-character:line-break">
 +
  <!--[endif]--><o:p></o:p></span></b></p>
 +
  </td>
 +
  <td width="45%" style="width:45.02%;border:solid windowtext 1.0pt;border-left:
 +
  none;mso-border-left-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
 +
  background:#FFF2CC;mso-background-themecolor:accent4;mso-background-themetint:
 +
  51;padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><b style="mso-bidi-font-weight:normal"><span lang="EN-AU" style="font-size:15.0pt;
 +
  font-family:Quicksand"><br>
 +
  COMPARISON WITH OUR SEQUENCE<br style="mso-special-character:line-break">
 +
  <!--[if !supportLineBreakNewLine]--><br style="mso-special-character:line-break">
 +
  <!--[endif]--><o:p></o:p></span></b></p>
 +
  </td>
 +
  <td width="6%" style="width:6.16%;border:solid windowtext 1.0pt;border-left:
 +
  none;mso-border-left-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
 +
  background:#FFF2CC;mso-background-themecolor:accent4;mso-background-themetint:
 +
  51;padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><b style="mso-bidi-font-weight:normal"><span lang="EN-AU" style="font-size:15.0pt;
 +
  font-family:Quicksand">Y/N<o:p></o:p></span></b></p>
 +
  </td>
 +
</tr>
 +
<tr style="mso-yfti-irow:1;height:12.75pt">
 +
  <td width="48%" style="width:48.82%;border:solid windowtext 1.0pt;border-top:
 +
  none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
 +
  padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><br>
 +
  Single-chain insulin for treatment of type 1 diabetes and type 2 diabetes
 +
  having the formula<br style="mso-special-character:line-break">
 +
  <!--[if !supportLineBreakNewLine]--><br style="mso-special-character:line-break">
 +
  <!--[endif]--><o:p></o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span class="GramE"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">B(</span></span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">1-26)- X<sub>1</sub>
 +
  - X<sub>2</sub> - X<sub>3</sub>- X<sub>4</sub>- A (1-21),<o:p></o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><br style="mso-special-character:
 +
  line-break">
 +
  <!--[if !supportLineBreakNewLine]--><br style="mso-special-character:line-break">
 +
  <!--[endif]--><o:p></o:p></span></p>
 +
  </td>
 +
  <td width="45%" style="width:45.02%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">B - linker - A formula<o:p></o:p></span></p>
 +
  </td>
 +
  <td width="6%" style="width:6.16%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;background:#E2EFD9;mso-background-themecolor:
 +
  accent6;mso-background-themetint:51;padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">Y<o:p></o:p></span></p>
 +
  </td>
 +
</tr>
 +
<tr style="mso-yfti-irow:2;height:12.75pt">
 +
  <td width="48%" style="width:48.82%;border:solid windowtext 1.0pt;border-top:
 +
  none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
 +
  padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><br>
 +
  <span class="GramE">B(</span>1-26) is a peptide chain <b style="mso-bidi-font-weight:
 +
  normal">consisting of the first 26 amino acid residues of the B chain of
 +
  human insulin</b> counted from the N-terminal end of the B chain or an
 +
  analogue of the B-chain with one addition or one deletion of one of the amino
 +
  acid residues in the B-chain or derivative of the B-chain being chemically
 +
  modified by introducing a group in the side chain in one or more positions of
 +
  the B-chain or by oxidation or reduction of the side chains of the amino
 +
  acids residues in the B-chain,<br style="mso-special-character:line-break">
 +
  <!--[if !supportLineBreakNewLine]--><br style="mso-special-character:line-break">
 +
  <!--[endif]--><o:p></o:p></span></p>
 +
  </td>
 +
  <td width="45%" style="width:45.02%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><br>
 +
  Our B chain consists of 28 AA. Although the patents contain different
 +
  versions <span class="SpellE">eg</span> </span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-fareast-font-family:Helvetica;
 +
  mso-bidi-font-family:Helvetica">‘</span><span lang="EN-AU" style="font-size:
 +
  14.0pt;font-family:Quicksand">an analogue of the B-chain with one addition or
 +
  deletion</span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;
 +
  mso-fareast-font-family:Helvetica;mso-bidi-font-family:Helvetica">’</span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"> </span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-fareast-font-family:
 +
  Helvetica;mso-bidi-font-family:Helvetica">–</span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"> the total length of the
 +
  B-chain must STILL be 26AA.<o:p></o:p></span></p>
 +
  </td>
 +
  <td width="6%" style="width:6.16%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;background:#FFC8CD;padding:0cm 5.4pt 0cm 5.4pt;
 +
  height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">N<o:p></o:p></span></p>
 +
  </td>
 +
</tr>
 +
<tr style="mso-yfti-irow:3;height:12.75pt">
 +
  <td width="48%" style="width:48.82%;border:solid windowtext 1.0pt;border-top:
 +
  none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
 +
  padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;color:black;mso-themecolor:
 +
  text1"><br>
 +
  and <span class="GramE">A(</span>1-21) is the natural insulin A chain or an
 +
  analogue thereof with one addition or one deletion of one of the amino acid
 +
  residues in the A-chain or derivative of the A-chain being chemically
 +
  modified by introducing a group in the side chain in one or more positions of
 +
  the A-chain or by oxidation or reduction of the side chains of the amino
 +
  acids residues in the A-chain, wherein<br style="mso-special-character:line-break">
 +
  <!--[if !supportLineBreakNewLine]--><br style="mso-special-character:line-break">
 +
  <!--[endif]--></span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p></o:p></span></p>
 +
  </td>
 +
  <td width="45%" style="width:45.02%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">In our sequence construct </span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-fareast-font-family:
 +
  Helvetica;mso-bidi-font-family:Helvetica">–</span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"> the A chain is 22 amino acids
 +
  long. Just like in the B-chain (it only covers a TOTAL of 21 AA). Even though
 +
  our A chain contains the addition of an amino acid (glycine), the length is
 +
  too long for the patent to operate over.<b style="mso-bidi-font-weight:normal"><o:p></o:p></b></span></p>
 +
  </td>
 +
  <td width="6%" style="width:6.16%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;background:#FFC8CD;padding:0cm 5.4pt 0cm 5.4pt;
 +
  height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">N<o:p></o:p></span></p>
 +
  </td>
 +
</tr>
 +
<tr style="mso-yfti-irow:4;height:12.75pt">
 +
  <td width="48%" style="width:48.82%;border:solid windowtext 1.0pt;border-top:
 +
  none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
 +
  padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><br>
 +
  X<sub>4 </sub>does not contain two adjacent basic amino acid residues and
 +
  wherein the single-chain insulin has an affinity to the human insulin
 +
  receptor of at least about 20% of that of human insulin if the single-chain
 +
  insulin molecule is not chemically modified by acylation.<br style="mso-special-character:line-break">
 +
  <!--[if !supportLineBreakNewLine]--><br style="mso-special-character:line-break">
 +
  <!--[endif]--><o:p></o:p></span></p>
 +
  </td>
 +
  <td width="45%" style="width:45.02%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">We have 2 adjacent basic amino
 +
  acid residues and the affinity cannot be tested<o:p></o:p></span></p>
 +
  </td>
 +
  <td width="6%" style="width:6.16%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;background:#FFC8CD;padding:0cm 5.4pt 0cm 5.4pt;
 +
  height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">N<o:p></o:p></span></p>
 +
  </td>
 +
</tr>
 +
<tr style="mso-yfti-irow:5;height:15.55pt">
 +
  <td width="48%" style="width:48.82%;border:solid windowtext 1.0pt;border-top:
 +
  none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
 +
  padding:0cm 5.4pt 0cm 5.4pt;height:15.55pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><br>
 +
  wherein X<sub>1</sub>&nbsp;is <span class="SpellE">Thr</span>, Lys or <span class="SpellE">Arg</span><br style="mso-special-character:line-break">
 +
  <!--[if !supportLineBreakNewLine]--><br style="mso-special-character:line-break">
 +
  <!--[endif]--><o:p></o:p></span></p>
 +
  </td>
 +
  <td width="45%" style="width:45.02%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt;height:15.55pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><br>
 +
  X<sub>1</sub> is glutamine<o:p></o:p></span></p>
 +
  </td>
 +
  <td width="6%" style="width:6.16%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;background:#FFC8CD;padding:0cm 5.4pt 0cm 5.4pt;
 +
  height:15.55pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">N<o:p></o:p></span></p>
 +
  </td>
 +
</tr>
 +
<tr style="mso-yfti-irow:6;height:12.75pt">
 +
  <td width="48%" style="width:48.82%;border:solid windowtext 1.0pt;border-top:
 +
  none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
 +
  padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><br>
 +
  X<sub>2</sub>&nbsp;is Pro, Lys or Asp,<br style="mso-special-character:line-break">
 +
  <!--[if !supportLineBreakNewLine]--><br style="mso-special-character:line-break">
 +
  <!--[endif]--><o:p></o:p></span></p>
 +
  </td>
 +
  <td width="45%" style="width:45.02%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><br>
 +
  X<sub>2 </sub>is arginine<o:p></o:p></span></p>
 +
  </td>
 +
  <td width="6%" style="width:6.16%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;background:#FFC8CD;padding:0cm 5.4pt 0cm 5.4pt;
 +
  height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">N<o:p></o:p></span></p>
 +
  </td>
 +
</tr>
 +
<tr style="mso-yfti-irow:7;height:12.75pt">
 +
  <td width="48%" style="width:48.82%;border:solid windowtext 1.0pt;border-top:
 +
  none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
 +
  padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><br>
 +
  X<sub>3</sub>&nbsp;is Lys, Pro or <span class="SpellE">Glu</span>,<o:p></o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  </td>
 +
  <td width="45%" style="width:45.02%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">X<sub>3</sub> is glycine<o:p></o:p></span></p>
 +
  </td>
 +
  <td width="6%" style="width:6.16%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;background:#FFC8CD;padding:0cm 5.4pt 0cm 5.4pt;
 +
  height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">N<o:p></o:p></span></p>
 +
  </td>
 +
</tr>
 +
<tr style="mso-yfti-irow:8;mso-yfti-lastrow:yes;height:12.75pt">
 +
  <td width="48%" style="width:48.82%;border:solid windowtext 1.0pt;border-top:
 +
  none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
 +
  padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">X<sub>4</sub>&nbsp;is a
 +
  peptide sequence with the following formula <span class="SpellE">X<sub>a</sub>-X<sub>b</sub>-X<sub>c</sub>-X<sub>d</sub>-X<sub>e</sub>-X<sub>f</sub>X<sub>g</sub></span>&nbsp;(SEQ
 +
  ID NO:129) wherein<o:p></o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoListParagraphCxSpFirst" align="center" style="text-align:center"><span class="SpellE"><span style="font-size:14.0pt;font-family:Quicksand;mso-ansi-language:
 +
  EN-GB">X<sub>a</sub></span></span><span style="font-size:14.0pt;font-family:
 +
  Quicksand;mso-ansi-language:EN-GB">&nbsp;is selected from the group
 +
  consisting of L, R, T, A, H, Q, G, S and V;<o:p></o:p></span></p>
 +
  <p class="MsoListParagraphCxSpMiddle" align="center" style="text-align:center"><span style="font-size:14.0pt;font-family:Quicksand;mso-ansi-language:EN-GB"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoListParagraphCxSpMiddle" align="center" style="text-align:center"><span class="SpellE"><span style="font-size:14.0pt;font-family:Quicksand;mso-ansi-language:
 +
  EN-GB">X<sub>b</sub></span></span><span style="font-size:14.0pt;font-family:
 +
  Quicksand;mso-ansi-language:EN-GB">&nbsp;is selected from the group
 +
  consisting of W, G, S, A, H, R, and T;<o:p></o:p></span></p>
 +
  <p class="MsoListParagraphCxSpMiddle" align="center" style="text-align:center"><span style="font-size:14.0pt;font-family:Quicksand;mso-ansi-language:EN-GB"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoListParagraphCxSpMiddle" align="center" style="text-align:center"><span class="SpellE"><span style="font-size:14.0pt;font-family:Quicksand;mso-ansi-language:
 +
  EN-GB">X<sub>c</sub></span></span><span style="font-size:14.0pt;font-family:
 +
  Quicksand;mso-ansi-language:EN-GB">&nbsp;is selected from the group
 +
  consisting of L, Y, M, H, R, T, Q, K, V, S, A, G and P;<o:p></o:p></span></p>
 +
  <p class="MsoListParagraphCxSpMiddle" align="center" style="text-align:center"><span style="font-size:14.0pt;font-family:Quicksand;mso-ansi-language:EN-GB"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoListParagraphCxSpMiddle" align="center" style="text-align:center"><span class="SpellE"><span style="font-size:14.0pt;font-family:Quicksand;mso-ansi-language:
 +
  EN-GB">X<sub>d</sub></span></span><span style="font-size:14.0pt;font-family:
 +
  Quicksand;mso-ansi-language:EN-GB">&nbsp;is selected from the group
 +
  consisting of R, A, Y, M, S, N, H, and G;<o:p></o:p></span></p>
 +
  <p class="MsoListParagraphCxSpMiddle" align="center" style="text-align:center"><span class="SpellE"><span style="font-size:14.0pt;font-family:Quicksand;mso-ansi-language:
 +
  EN-GB">X<sub>e</sub></span></span><span style="font-size:14.0pt;font-family:
 +
  Quicksand;mso-ansi-language:EN-GB">&nbsp;is selected from the group
 +
  consisting of S, R, A, T, K, P, N, M, H, Q, V, and G;<o:p></o:p></span></p>
 +
  <p class="MsoListParagraphCxSpMiddle" align="center" style="text-align:center"><span style="font-size:14.0pt;font-family:Quicksand;mso-ansi-language:EN-GB"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoListParagraphCxSpMiddle" align="center" style="text-align:center"><span class="SpellE"><span style="font-size:14.0pt;font-family:Quicksand;mso-ansi-language:
 +
  EN-GB">X<sub>f</sub></span></span><span style="font-size:14.0pt;font-family:
 +
  Quicksand;mso-ansi-language:EN-GB">&nbsp;is selected from the group
 +
  consisting of G and A; and<o:p></o:p></span></p>
 +
  <p class="MsoListParagraphCxSpMiddle" align="center" style="text-align:center"><span style="font-size:14.0pt;font-family:Quicksand;mso-ansi-language:EN-GB"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoListParagraphCxSpLast" align="center" style="text-align:center"><span class="SpellE"><span style="font-size:14.0pt;font-family:Quicksand;mso-ansi-language:
 +
  EN-GB">X<sub>g</sub></span></span><span style="font-size:14.0pt;font-family:
 +
  Quicksand;mso-ansi-language:EN-GB">&nbsp;is selected from the group
 +
  consisting of K, R, P, H, F, T, I, Q, W, and A,<o:p></o:p></span></p>
 +
  </td>
 +
  <td width="45%" style="width:45.02%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">The total linker length that
 +
  can be formulated from <span class="SpellE">X<sub>a</sub></span><sub> </sub>– <span class="SpellE">X<sub>g</sub></span> is 7 amino acids with the three other
 +
  residues for X<sub>1</sub> – X<sub>3</sub>. This totals to a maximum linker
 +
  length of 10 amino acids. Our linker is <b style="mso-bidi-font-weight:normal">12
 +
  amino</b> acids long.<o:p></o:p></span></p>
 +
  </td>
 +
  <td width="6%" style="width:6.16%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;background:#FFC8CD;padding:0cm 5.4pt 0cm 5.4pt;
 +
  height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">N<o:p></o:p></span></p>
 +
  </td>
 +
</tr>
 +
</tbody></table>
 +
</div>
 +
    <div class="patent_4 box">
 +
    <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
    <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
    <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
<p class="MsoNormal" align="center" style="text-align:center"><b style="mso-bidi-font-weight:
 +
normal"><span lang="EN-AU" style="font-size:20.0pt;font-family:Quicksand">WEISS
 +
ET AL.<o:p></o:p></span></b></p>
 +
 
 +
<p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:16.0pt;font-family:Quicksand">Fibrillation-resistant insulin
 +
and insulin analogues&nbsp;<br>
 +
Patent No: <b style="mso-bidi-font-weight:normal">EP 2074140 B1</b><o:p></o:p></span></p>
 +
 
 +
<p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:16.0pt;font-family:Quicksand">April 6th, 2009<o:p></o:p></span></p>
 +
 
 +
<p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
 
 +
<table class="MsoTableGrid" border="1" cellspacing="0" cellpadding="0" width="100%" style="width:100.0%;border-collapse:collapse;border:none;mso-border-alt:solid windowtext .5pt;
 +
mso-yfti-tbllook:1184;mso-padding-alt:0cm 5.4pt 0cm 5.4pt">
 +
<tbody><tr style="mso-yfti-irow:0;mso-yfti-firstrow:yes;height:55.45pt">
 +
  <td width="47%" style="width:47.74%;border:solid windowtext 1.0pt;mso-border-alt:
 +
  solid windowtext .5pt;background:#A1C4C8;padding:0cm 5.4pt 0cm 5.4pt;
 +
  height:55.45pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><b style="mso-bidi-font-weight:normal"><span lang="EN-AU" style="font-size:15.0pt;
 +
  font-family:Quicksand"><o:p>&nbsp;</o:p></span></b></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><b style="mso-bidi-font-weight:normal"><span lang="EN-AU" style="font-size:15.0pt;
 +
  font-family:Quicksand">CLAIM<br style="mso-special-character:line-break">
 +
  <!--[if !supportLineBreakNewLine]--><br style="mso-special-character:line-break">
 +
  <!--[endif]--><o:p></o:p></span></b></p>
 +
  </td>
 +
  <td width="46%" style="width:46.08%;border:solid windowtext 1.0pt;border-left:
 +
  none;mso-border-left-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
 +
  background:#A1C4C8;padding:0cm 5.4pt 0cm 5.4pt;height:55.45pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><b style="mso-bidi-font-weight:normal"><span lang="EN-AU" style="font-size:15.0pt;
 +
  font-family:Quicksand"><br>
 +
  COMPARISON WITH OUR SEQUENCE<br style="mso-special-character:line-break">
 +
  <!--[if !supportLineBreakNewLine]--><br style="mso-special-character:line-break">
 +
  <!--[endif]--><o:p></o:p></span></b></p>
 +
  </td>
 +
  <td width="6%" style="width:6.18%;border:solid windowtext 1.0pt;border-left:
 +
  none;mso-border-left-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
 +
  background:#A1C4C8;padding:0cm 5.4pt 0cm 5.4pt;height:55.45pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><b style="mso-bidi-font-weight:normal"><span lang="EN-AU" style="font-size:15.0pt;
 +
  font-family:Quicksand">Y/N<o:p></o:p></span></b></p>
 +
  </td>
 +
</tr>
 +
<tr style="mso-yfti-irow:1;height:86.8pt">
 +
  <td width="47%" style="width:47.74%;border:solid windowtext 1.0pt;border-top:
 +
  none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
 +
  padding:0cm 5.4pt 0cm 5.4pt;height:86.8pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">An insulin analogue comprising
 +
  a single chain polypeptide containing an insulin A-chain polypeptide and an
 +
  insulin B-chain polypeptide connected by a truncated linker,<o:p></o:p></span></p>
 +
  </td>
 +
  <td width="46%" style="width:46.08%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt;height:86.8pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">Our linker is truncated from
 +
  the entire C-peptide to 12 amino acids and has the general formula of B-X-A
 +
  where our linker is<o:p></o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">QRGGGSGGGQRR<o:p></o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  </td>
 +
  <td width="6%" rowspan="2" style="width:6.18%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;background:#E2EFD9;mso-background-themecolor:
 +
  accent6;mso-background-themetint:51;padding:0cm 5.4pt 0cm 5.4pt;height:86.8pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">Y<o:p></o:p></span></p>
 +
  </td>
 +
</tr>
 +
<tr style="mso-yfti-irow:2;height:8.6pt">
 +
  <td width="93%" colspan="2" style="width:93.82%;border:solid windowtext 1.0pt;
 +
  border-top:none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
 +
  padding:0cm 5.4pt 0cm 5.4pt;height:8.6pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">wherein the truncated linker
 +
  is a polypeptide selected from the group consisting of:<o:p></o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  </td>
 +
</tr>
 +
<tr style="mso-yfti-irow:3;height:12.05pt">
 +
  <td width="47%" style="width:47.74%;border:solid windowtext 1.0pt;border-top:
 +
  none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
 +
  padding:0cm 5.4pt 0cm 5.4pt;height:12.05pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">a polypeptide having the
 +
  sequence GGGPRR<o:p></o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  </td>
 +
  <td width="46%" style="width:46.08%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt;height:12.05pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">No proline<o:p></o:p></span></p>
 +
  </td>
 +
  <td width="6%" style="width:6.18%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;background:#FFC8CD;padding:0cm 5.4pt 0cm 5.4pt;
 +
  height:12.05pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">N<o:p></o:p></span></p>
 +
  </td>
 +
</tr>
 +
<tr style="mso-yfti-irow:4;height:12.75pt">
 +
  <td width="47%" style="width:47.74%;border:solid windowtext 1.0pt;border-top:
 +
  none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
 +
  padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">a polypeptide having the
 +
  sequence GGPRR<o:p></o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  </td>
 +
  <td width="46%" style="width:46.08%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">No proline<o:p></o:p></span></p>
 +
  </td>
 +
  <td width="6%" style="width:6.18%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;background:#FFC8CD;padding:0cm 5.4pt 0cm 5.4pt;
 +
  height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">N<o:p></o:p></span></p>
 +
  </td>
 +
</tr>
 +
<tr style="mso-yfti-irow:5;height:5.05pt">
 +
  <td width="47%" style="width:47.74%;border:solid windowtext 1.0pt;border-top:
 +
  none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
 +
  padding:0cm 5.4pt 0cm 5.4pt;height:5.05pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">a polypeptide having the
 +
  sequence GSEQRR<o:p></o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  </td>
 +
  <td width="46%" style="width:46.08%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt;height:5.05pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">No glutamate<o:p></o:p></span></p>
 +
  </td>
 +
  <td width="6%" style="width:6.18%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;background:#FFC8CD;padding:0cm 5.4pt 0cm 5.4pt;
 +
  height:5.05pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">N<o:p></o:p></span></p>
 +
  </td>
 +
</tr>
 +
<tr style="mso-yfti-irow:6;height:12.75pt">
 +
  <td width="47%" style="width:47.74%;border:solid windowtext 1.0pt;border-top:
 +
  none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
 +
  padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">a polypeptide having the
 +
  sequence RREQR<o:p></o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  </td>
 +
  <td width="46%" style="width:46.08%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">No glutamate<o:p></o:p></span></p>
 +
  </td>
 +
  <td width="6%" style="width:6.18%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;background:#FFC8CD;padding:0cm 5.4pt 0cm 5.4pt;
 +
  height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">N<o:p></o:p></span></p>
 +
  </td>
 +
</tr>
 +
<tr style="mso-yfti-irow:7;height:12.75pt">
 +
  <td width="47%" style="width:47.74%;border:solid windowtext 1.0pt;border-top:
 +
  none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
 +
  padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">a polypeptide having the
 +
  sequence RREALQKR<o:p></o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  </td>
 +
  <td width="46%" style="width:46.08%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">No glutamate<o:p></o:p></span></p>
 +
  </td>
 +
  <td width="6%" style="width:6.18%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;background:#FFC8CD;padding:0cm 5.4pt 0cm 5.4pt;
 +
  height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">N<o:p></o:p></span></p>
 +
  </td>
 +
</tr>
 +
<tr style="mso-yfti-irow:8;height:27.45pt">
 +
  <td width="47%" style="width:47.74%;border:solid windowtext 1.0pt;border-top:
 +
  none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
 +
  padding:0cm 5.4pt 0cm 5.4pt;height:27.45pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">a polypeptide having the
 +
  sequence GAGPRR<o:p></o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  </td>
 +
  <td width="46%" style="width:46.08%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt;height:27.45pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">No proline<o:p></o:p></span></p>
 +
  </td>
 +
  <td width="6%" style="width:6.18%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;background:#FFC8CD;padding:0cm 5.4pt 0cm 5.4pt;
 +
  height:27.45pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">N<o:p></o:p></span></p>
 +
  </td>
 +
</tr>
 +
<tr style="mso-yfti-irow:9;height:12.75pt">
 +
  <td width="47%" style="width:47.74%;border:solid windowtext 1.0pt;border-top:
 +
  none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
 +
  padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">a polypeptide having the
 +
  sequence GPRR<o:p></o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  </td>
 +
  <td width="46%" style="width:46.08%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">No proline<o:p></o:p></span></p>
 +
  </td>
 +
  <td width="6%" style="width:6.18%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;background:#FFC8CD;padding:0cm 5.4pt 0cm 5.4pt;
 +
  height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">N<o:p></o:p></span></p>
 +
  </td>
 +
</tr>
 +
<tr style="mso-yfti-irow:10;height:30.95pt">
 +
  <td width="47%" style="width:47.74%;border:solid windowtext 1.0pt;border-top:
 +
  none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
 +
  padding:0cm 5.4pt 0cm 5.4pt;height:30.95pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">wherein the insulin B-chain
 +
  polypeptide optionally contains one or more of:<br style="mso-special-character:
 +
  line-break">
 +
  <!--[if !supportLineBreakNewLine]--><br style="mso-special-character:line-break">
 +
  <!--[endif]--><o:p></o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">an aspartate substitution at
 +
  the position corresponding to position B10 of insulin,<br style="mso-special-character:
 +
  line-break">
 +
  <!--[if !supportLineBreakNewLine]--><br style="mso-special-character:line-break">
 +
  <!--[endif]--><o:p></o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">a lysine or an aspartate
 +
  substitution at the position corresponding to position B28 of insulin, and<br style="mso-special-character:line-break">
 +
  <!--[if !supportLineBreakNewLine]--><br style="mso-special-character:line-break">
 +
  <!--[endif]--><o:p></o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">a proline substitution at the
 +
  position corresponding to position B29 of insulin<o:p></o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  </td>
 +
  <td width="46%" style="width:46.08%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt;height:30.95pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">Our B-chain is native human
 +
  insulin<o:p></o:p></span></p>
 +
  </td>
 +
  <td width="6%" style="width:6.18%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;background:#FFC8CD;padding:0cm 5.4pt 0cm 5.4pt;
 +
  height:30.95pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">N<o:p></o:p></span></p>
 +
  </td>
 +
</tr>
 +
<tr style="mso-yfti-irow:11;mso-yfti-lastrow:yes;height:12.75pt">
 +
  <td width="47%" style="width:47.74%;border:solid windowtext 1.0pt;border-top:
 +
  none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
 +
  padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><br>
 +
  and wherein the insulin A-chain polypeptide contains a histidine substitution
 +
  at the position corresponding to position A8 of insulin.<br style="mso-special-character:
 +
  line-break">
 +
  <!--[if !supportLineBreakNewLine]--><br style="mso-special-character:line-break">
 +
  <!--[endif]--><o:p></o:p></span></p>
 +
  </td>
 +
  <td width="46%" style="width:46.08%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">Our A-chain does not contain
 +
  the relevant substitution and only an additional glycine<o:p></o:p></span></p>
 +
  </td>
 +
  <td width="6%" style="width:6.18%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;background:#FFC8CD;padding:0cm 5.4pt 0cm 5.4pt;
 +
  height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">N<o:p></o:p></span></p>
 +
  </td>
 +
</tr>
 +
</tbody></table> </div>
 +
    <div class="patent_5 box">
 +
    <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
    <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
    <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
   
 +
<p class="MsoNormal" align="center" style="text-align:center"><b style="mso-bidi-font-weight:
 +
normal"><span lang="EN-AU" style="font-size:20.0pt;font-family:Quicksand">STOWELL
 +
ET AL.</span></b><span lang="EN-AU" style="font-size:20.0pt;font-family:Quicksand"><o:p></o:p></span></p>
 +
 
 +
<p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:16.0pt;font-family:Quicksand">Chemically and thermodynamically
 +
stable insulin analogues and improved<o:p></o:p></span></p>
 +
 
 +
<p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:16.0pt;font-family:Quicksand">methods for their production<o:p></o:p></span></p>
 +
 
 +
<p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:16.0pt;font-family:Quicksand">Patent No: <b style="mso-bidi-font-weight:
 +
normal">US 9006176 B2</b><o:p></o:p></span></p>
 +
 
 +
<p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:16.0pt;font-family:Quicksand">October <span class="GramE">16<sup>th</sup></span>
 +
2012<o:p></o:p></span></p>
 +
 
 +
<table class="MsoTableGrid" border="1" cellspacing="0" cellpadding="0" width="100%" style="width:100.0%;border-collapse:collapse;border:none;mso-border-alt:solid windowtext .5pt;
 +
mso-yfti-tbllook:1184;mso-padding-alt:0cm 5.4pt 0cm 5.4pt">
 +
<tbody><tr style="mso-yfti-irow:0;mso-yfti-firstrow:yes;height:14.85pt">
 +
  <td width="48%" style="width:48.32%;border:solid windowtext 1.0pt;mso-border-alt:
 +
  solid windowtext .5pt;background:#BBB8EB;padding:0cm 5.4pt 0cm 5.4pt;
 +
  height:14.85pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:15.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:15.0pt;font-family:Quicksand">CLAIM<br style="mso-special-character:
 +
  line-break">
 +
  <!--[if !supportLineBreakNewLine]--><br style="mso-special-character:line-break">
 +
  <!--[endif]--><o:p></o:p></span></p>
 +
  </td>
 +
  <td width="45%" style="width:45.14%;border:solid windowtext 1.0pt;border-left:
 +
  none;mso-border-left-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
 +
  background:#BBB8EB;padding:0cm 5.4pt 0cm 5.4pt;height:14.85pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:15.0pt;font-family:Quicksand"><br>
 +
  COMPARISON WITH OUR SEQUENCE<br style="mso-special-character:line-break">
 +
  <!--[if !supportLineBreakNewLine]--><br style="mso-special-character:line-break">
 +
  <!--[endif]--><o:p></o:p></span></p>
 +
  </td>
 +
  <td width="6%" style="width:6.54%;border:solid windowtext 1.0pt;border-left:
 +
  none;mso-border-left-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
 +
  background:#BBB8EB;padding:0cm 5.4pt 0cm 5.4pt;height:14.85pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:15.0pt;font-family:Quicksand">Y/N<o:p></o:p></span></p>
 +
  </td>
 +
</tr>
 +
<tr style="mso-yfti-irow:1;height:12.75pt">
 +
  <td width="48%" style="width:48.32%;border:solid windowtext 1.0pt;border-top:
 +
  none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
 +
  padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">A single chain insulin (SCI)
 +
  compound of formula a(I):<o:p></o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">B chain - C</span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-fareast-font-family:
 +
  Helvetica;mso-bidi-font-family:Helvetica">’</span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"> – A Chain (Formula (I))<o:p></o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">having the properties of
 +
  higher affinity for the insulin receptor and lower affinity for the IGF-1
 +
  receptor as compared to those of native proinsulin with chemical and
 +
  thermodynamic degradation profiles such that the SCI can be formulated and
 +
  stored for extended periods of time without refrigeration;<o:p></o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  </td>
 +
  <td width="45%" style="width:45.14%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">Correct linker formulation of
 +
  B-linker-A<o:p></o:p></span></p>
 +
  </td>
 +
  <td width="6%" style="width:6.54%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;background:#E2EFD9;mso-background-themecolor:
 +
  accent6;mso-background-themetint:51;padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">Y<o:p></o:p></span></p>
 +
  </td>
 +
</tr>
 +
<tr style="mso-yfti-irow:2;height:12.75pt">
 +
  <td width="48%" style="width:48.32%;border:solid windowtext 1.0pt;border-top:
 +
  none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
 +
  padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">W herein B chain and A chain
 +
  are modified human insulin chains; and<o:p></o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  </td>
 +
  <td width="45%" style="width:45.14%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  </td>
 +
  <td width="6%" style="width:6.54%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;background:#E2EFD9;mso-background-themecolor:
 +
  accent6;mso-background-themetint:51;padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">Y<o:p></o:p></span></p>
 +
  </td>
 +
</tr>
 +
<tr style="mso-yfti-irow:3;height:12.75pt">
 +
  <td width="48%" style="width:48.32%;border:solid windowtext 1.0pt;border-top:
 +
  none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
 +
  padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">Wherein C</span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-fareast-font-family:
 +
  Helvetica;mso-bidi-font-family:Helvetica">’</span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"> covalently links the
 +
  C-terminus of the B chain to the N-terminus of the A chain, and is a peptide
 +
  of 5 amino acids comprising the following sequence: Y-P-G-D-X (SEQ ID NO: 1);
 +
  wherein X is any amino acid;<o:p></o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  </td>
 +
  <td width="45%" style="width:45.14%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">No proline (P) and no aspartic
 +
  acid (D)<o:p></o:p></span></p>
 +
  </td>
 +
  <td width="6%" style="width:6.54%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;background:#FFC8CD;padding:0cm 5.4pt 0cm 5.4pt;
 +
  height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">N<o:p></o:p></span></p>
 +
  </td>
 +
</tr>
 +
<tr style="mso-yfti-irow:4;mso-yfti-lastrow:yes;height:12.75pt">
 +
  <td width="48%" style="width:48.32%;border:solid windowtext 1.0pt;border-top:
 +
  none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
 +
  padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">wherein the B chain is
 +
  modified from a native human insulin B chain (SEQ ID NO:11), and A chain is
 +
  modified from a native human insulin A chain (SEQ ID NO:10), wherein the
 +
  modifications comprise one or more mutations at<o:p></o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">(1) Gln5, Gln15, Asn18, or
 +
  Asn21 of SEQ ID NO:10, or<o:p></o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">(2) Asn3 or Gln5 of SEQ ID
 +
  NO:11; resulting in enhanced resistance to <span class="SpellE">deamidation</span>.<o:p></o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  </td>
 +
  <td width="45%" style="width:45.14%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt;height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p>&nbsp;</o:p></span></p>
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">B is not modified and A chain
 +
  does not have similar modifications, rather an addition at residue 1 without
 +
  the purpose of resisting deamination.<o:p></o:p></span></p>
 +
  </td>
 +
  <td width="6%" style="width:6.54%;border-top:none;border-left:none;
 +
  border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
 +
  mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
 +
  mso-border-alt:solid windowtext .5pt;background:#FFC8CD;padding:0cm 5.4pt 0cm 5.4pt;
 +
  height:12.75pt">
 +
  <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">N<o:p></o:p></span></p>
 +
  </td>
 +
</tr>
 +
</tbody></table> </div>
  
 
</body>
 
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Revision as of 12:31, 25 October 2017

 

 

 

GENERAL PATENT STUFF

DIMARCHI ET AL.

Single Chain Insulin with high bioactivity

Patent No: US 9458,220 B2

October 4th 2016

 

 

CLAIM


COMPARISON WITH OUR SEQUENCE

Y/N

 

A single chain insulin agonist analogue with stricture of B-LM-A wherein B represents an insulin B chain comprising the sequence R22X25LCGX29…  and A represents an insulin A chain comprising the sequence

GIVX4X5CCX8…-R13

 

Both insulin A and B chains involve R groups which stand for modifications eg. carboxylation. As our insulin B chain does not contain any modifications (except an additional glycine at the A chain), our construct is outside the patent

 

 

 

 

N

 

Furthermore the linking moiety linking the carboxy terminus of the B chain to the amino terminus of the A chain; further wherein the linking moiety is an 8 amino acid sequence comprising of the sequence X51X52GSSSX57X58 wherein

X51 = group consisting of glycine, alanine, valine, leucine, isoleucine, isoleucine and ornithine

X52 = any amino acid other than tyrosine

X57 and X58 are independently selected form the ground consisting of arginine, lysine and ornithine

 

 

Our amino acid sequence is squarely outside the scope of 8 amino acids.

 

Even if we did fall within the claim; we do not contain the 8 amino acid sequence using both potential orientations

 

X51 is glutamine or arginine in our sequence

 

 

B-chain – QR . . . RR – A-chain

 

 

 

 

 

N

 

The LM also requires the sequence of GAGSSSRR or a sequence that differs from GAGSSRR by 1 or 2 amino acids

 

Our sequence is 12 amino acids long and differs by more than 4 amino acids.

N

 

LM represents linking moiety linking the carboxyl terminus of the B chain to the amino terminus of the a chain, wherein said linking moiety is an 8 amino acid sequence consisting of X51X52X53X54... wherein X51 is selected from the group consisting of glycine, alanine, valine, leucine, isoleucine and proline…

 

Similarly, the patent claim is over an 8 amino acid sequence. Applying the same principle our;

 

X51 is glutamine or arginine (depending on orientation) and outside the scope

N

 

 

 

LEE ET AL.

Single Chain Insulin Analog and a polynucleotide sequence encoding the analog

Patent No: US 6,630,348 B1

October 7th 2003

 

 

CLAIM


COMPARISON WITH OUR SEQUENCE

Y/N

 

A single chain insulin analogue compound of formula (I) having the properties of greater insulin receptor binding activity than proinsulin and less insulin receptor binding activity than insulin:


B chain -  X – A chain wherein:

 

General B – X – A chain single chain formula

Y

 

B and A chain are human insulin chains, respectively and,

 

 

Our B and A chain are human insulin chains although our A chain includes a modification (additional glycine)

 

N

X is a joining peptide of about 5 to 18 amino acids comprising the following sequence: Gly-Gly-Gly-Pro-Gly- Lys-Arg

 

Where the term ‘comprising’ is included, the patent requires that the specific sequence named MUST be part of the linker region.

 

Although our sequence is 12 amino acids long, it does not contain the ‘GGGPGLR’ identified in the patent

 

N

 

 

 

LEE ET AL.

Single Chain Insulin Analogs

Patent No: EP 1 193 272 B1

October 30th 2004

 

 

CLAIM


COMPARISON WITH OUR SEQUENCE

Y/N

 

A single chain insulin analogue compound of formula (I) having the properties of greater insulin receptor binding activity than prosinsulin and less insulin receptor binding activity than insulin:

 

B Chain – UI – Zn – Y – ZI – Un – A chain

 

 

 

B and A chain are human insulin chains respectively and

 

 

We have a modified A chain

N

 

U is an arginine or lysine residue

 

Our ‘U’ is glutamine

N

 

Z is a glycine

 

 

Z Is Glycine

Y

 

 

I is an integer of 2 – n

N is an integer of 0 or 2 and

 

The maximum size of the linker sequence when considering this is 9 amino acids. Since our sequence is 12 amino acids they are outside the scope

 

N

 

Y is glycine-proline-glycine, or alanine-proline-glycine-aspartic acid–valine, or tyrosine-proline-glycine-aspartic acid-valine, or histidine-proline-glycine-aspartic acid-valine.

 

 

 

Our sequence has no proline

 

N

 

 

 

KJELDSEN ET AL.

Single Chain insulin

Patent No: EP 1692168 B1

December 3rd, 2004

 

 

CLAIM


COMPARISON WITH OUR SEQUENCE

Y/N


Single-chain insulin for treatment of type 1 diabetes and type 2 diabetes having the formula

B(1-26)- X1 - X2 - X3- X4- A (1-21),

B - linker - A formula

Y


B(1-26) is a peptide chain consisting of the first 26 amino acid residues of the B chain of human insulin counted from the N-terminal end of the B chain or an analogue of the B-chain with one addition or one deletion of one of the amino acid residues in the B-chain or derivative of the B-chain being chemically modified by introducing a group in the side chain in one or more positions of the B-chain or by oxidation or reduction of the side chains of the amino acids residues in the B-chain,


Our B chain consists of 28 AA. Although the patents contain different versions eg ‘an analogue of the B-chain with one addition or deletion’ – the total length of the B-chain must STILL be 26AA.

N


and A(1-21) is the natural insulin A chain or an analogue thereof with one addition or one deletion of one of the amino acid residues in the A-chain or derivative of the A-chain being chemically modified by introducing a group in the side chain in one or more positions of the A-chain or by oxidation or reduction of the side chains of the amino acids residues in the A-chain, wherein

In our sequence construct – the A chain is 22 amino acids long. Just like in the B-chain (it only covers a TOTAL of 21 AA). Even though our A chain contains the addition of an amino acid (glycine), the length is too long for the patent to operate over.

N


X4 does not contain two adjacent basic amino acid residues and wherein the single-chain insulin has an affinity to the human insulin receptor of at least about 20% of that of human insulin if the single-chain insulin molecule is not chemically modified by acylation.

We have 2 adjacent basic amino acid residues and the affinity cannot be tested

N


wherein X1 is Thr, Lys or Arg


X1 is glutamine

N


X2 is Pro, Lys or Asp,


X2 is arginine

N


X3 is Lys, Pro or Glu,

 

 

X3 is glycine

N

 

X4 is a peptide sequence with the following formula Xa-Xb-Xc-Xd-Xe-XfXg (SEQ ID NO:129) wherein

 

Xa is selected from the group consisting of L, R, T, A, H, Q, G, S and V;

 

Xb is selected from the group consisting of W, G, S, A, H, R, and T;

 

Xc is selected from the group consisting of L, Y, M, H, R, T, Q, K, V, S, A, G and P;

 

Xd is selected from the group consisting of R, A, Y, M, S, N, H, and G;

Xe is selected from the group consisting of S, R, A, T, K, P, N, M, H, Q, V, and G;

 

Xf is selected from the group consisting of G and A; and

 

Xg is selected from the group consisting of K, R, P, H, F, T, I, Q, W, and A,

The total linker length that can be formulated from Xa – Xg is 7 amino acids with the three other residues for X1 – X3. This totals to a maximum linker length of 10 amino acids. Our linker is 12 amino acids long.

N

 

 

 

WEISS ET AL.

Fibrillation-resistant insulin and insulin analogues 
Patent No: EP 2074140 B1

April 6th, 2009

 

 

CLAIM


COMPARISON WITH OUR SEQUENCE

Y/N

An insulin analogue comprising a single chain polypeptide containing an insulin A-chain polypeptide and an insulin B-chain polypeptide connected by a truncated linker,

 

Our linker is truncated from the entire C-peptide to 12 amino acids and has the general formula of B-X-A where our linker is

QRGGGSGGGQRR

 

Y

 

wherein the truncated linker is a polypeptide selected from the group consisting of:

 

 

a polypeptide having the sequence GGGPRR

 

No proline

N

 

a polypeptide having the sequence GGPRR

 

No proline

N

 

a polypeptide having the sequence GSEQRR

 

No glutamate

N

 

a polypeptide having the sequence RREQR

 

No glutamate

N

 

a polypeptide having the sequence RREALQKR

 

No glutamate

N

 

a polypeptide having the sequence GAGPRR

 

No proline

N

 

a polypeptide having the sequence GPRR

 

No proline

N

 

wherein the insulin B-chain polypeptide optionally contains one or more of:

an aspartate substitution at the position corresponding to position B10 of insulin,

a lysine or an aspartate substitution at the position corresponding to position B28 of insulin, and

a proline substitution at the position corresponding to position B29 of insulin

 

Our B-chain is native human insulin

N


and wherein the insulin A-chain polypeptide contains a histidine substitution at the position corresponding to position A8 of insulin.

Our A-chain does not contain the relevant substitution and only an additional glycine

N

 

 

 

STOWELL ET AL.

Chemically and thermodynamically stable insulin analogues and improved

methods for their production

Patent No: US 9006176 B2

October 16th 2012

 

CLAIM


COMPARISON WITH OUR SEQUENCE

Y/N

 

A single chain insulin (SCI) compound of formula a(I):

 

B chain - C’ – A Chain (Formula (I))

 

having the properties of higher affinity for the insulin receptor and lower affinity for the IGF-1 receptor as compared to those of native proinsulin with chemical and thermodynamic degradation profiles such that the SCI can be formulated and stored for extended periods of time without refrigeration;

 

 

 

 

 

 

 

 

Correct linker formulation of B-linker-A

Y

 

W herein B chain and A chain are modified human insulin chains; and

 

 

Y

 

Wherein C’ covalently links the C-terminus of the B chain to the N-terminus of the A chain, and is a peptide of 5 amino acids comprising the following sequence: Y-P-G-D-X (SEQ ID NO: 1); wherein X is any amino acid;

 

No proline (P) and no aspartic acid (D)

N

 

wherein the B chain is modified from a native human insulin B chain (SEQ ID NO:11), and A chain is modified from a native human insulin A chain (SEQ ID NO:10), wherein the modifications comprise one or more mutations at

 

(1) Gln5, Gln15, Asn18, or Asn21 of SEQ ID NO:10, or

 

(2) Asn3 or Gln5 of SEQ ID NO:11; resulting in enhanced resistance to deamidation.

 

 

 

 

 

B is not modified and A chain does not have similar modifications, rather an addition at residue 1 without the purpose of resisting deamination.

N