|
|
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| </div> | | </div> |
| | | |
| + | <html> |
| <head> | | <head> |
| <script src="http://code.jquery.com/jquery-2.1.0.min.js"></script> | | <script src="http://code.jquery.com/jquery-2.1.0.min.js"></script> |
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| $(".patent_1").show(); | | $(".patent_1").show(); |
| } | | } |
− | if($(this).attr("value")=="2"){ | + | if($(this).attr("value")=="green"){ |
| $(".box").hide(); | | $(".box").hide(); |
| $(".patent_2").show(); | | $(".patent_2").show(); |
| } | | } |
− | if($(this).attr("value")=="3"){ | + | if($(this).attr("value")=="blue"){ |
| $(".box").hide(); | | $(".box").hide(); |
| $(".patent_3").show(); | | $(".patent_3").show(); |
| } | | } |
− | if($(this).attr("value")=="4"){ | + | if($(this).attr("value")=="choose"){ |
| $(".box").hide(); | | $(".box").hide(); |
− | $(".patent_4").show(); | + | $(".choose").show(); |
− | }
| + | |
− | if($(this).attr("value")=="5"){
| + | |
− | $(".box").hide();
| + | |
− | $(".patent_5").show();
| + | |
| } | | } |
| }); | | }); |
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| select { | | select { |
| width:20%; | | width:20%; |
− | height:10vh;
| |
| background-color:#e2e2e2; | | background-color:#e2e2e2; |
| position:absolute; | | position:absolute; |
| left:40%; | | left:40%; |
| } | | } |
− |
| |
| </style> | | </style> |
| </head> | | </head> |
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| <select> | | <select> |
| <option value="choose">Choose Patent</option> | | <option value="choose">Choose Patent</option> |
− | <option value="1">Lee et al. (2003)</option> | + | <option value="1">Dimarchi</option> |
− | <option value="2">Lee et al. (2004)</option> | + | <option value="2">2nd patent</option> |
− | <option value="3">Kjeldsen et al. (2004)</option> | + | <option value="3">3rd patent</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"> | + | <div class="choose box">DI MARCHI |
| + | |
| <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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| 2016<o:p></o:p></span></p> | | 2016<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> </o:p></span></p> | + | <p class="MsoNormal"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><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; | | <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"> | | 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:16.25pt"> | | <tbody><tr style="mso-yfti-irow:0;mso-yfti-firstrow:yes;height:16.25pt"> |
− | <td width="50%" style="width:50.94%;border:solid windowtext 1.0pt;mso-border-alt: | + | <td width="49%" style="width:49.92%;border:solid windowtext 1.0pt;mso-border-alt: |
− | solid windowtext .5pt;background:#FFF2CC;mso-background-themecolor:accent4; | + | solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt;height:16.25pt"> |
− | mso-background-themetint:51;padding:0cm 5.4pt 0cm 5.4pt;height:16.25pt">
| + | <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:15.0pt;font-family:Quicksand"><o:p> </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:15.0pt; | + | <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: |
− | font-family:Quicksand"><o:p> </o:p></span></b></p>
| + | line-break"> |
− | <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"> | | <!--[if !supportLineBreakNewLine]--><br style="mso-special-character:line-break"> |
− | <!--[endif]--></span></b><b style="mso-bidi-font-weight:normal"><span lang="EN-AU" style="font-size:11.0pt;font-family:Quicksand"><o:p></o:p></span></b></p> | + | <!--[endif]--></span><span lang="EN-AU" style="font-size:11.0pt;font-family:Quicksand"><o:p></o:p></span></p> |
| </td> | | </td> |
− | <td width="43%" style="width:43.5%;border:solid windowtext 1.0pt;border-left: | + | <td width="42%" style="width:42.66%;border:solid windowtext 1.0pt;border-left: |
| none;mso-border-left-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt; | | none;mso-border-left-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt; |
− | background:#FFF2CC;mso-background-themecolor:accent4;mso-background-themetint: | + | padding:0cm 5.4pt 0cm 5.4pt;height:16.25pt"> |
− | 51;padding:0cm 5.4pt 0cm 5.4pt;height:16.25pt">
| + | <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:15.0pt;font-family:Quicksand"><br> |
− | <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"> | | COMPARISON WITH OUR SEQUENCE<br style="mso-special-character:line-break"> |
| <!--[if !supportLineBreakNewLine]--><br style="mso-special-character:line-break"> | | <!--[if !supportLineBreakNewLine]--><br style="mso-special-character:line-break"> |
− | <!--[endif]--></span></b><b style="mso-bidi-font-weight:normal"><span lang="EN-AU" style="font-size:11.0pt;font-family:Quicksand"><o:p></o:p></span></b></p> | + | <!--[endif]--></span><span lang="EN-AU" style="font-size:11.0pt;font-family:Quicksand"><o:p></o:p></span></p> |
| </td> | | </td> |
− | <td width="5%" style="width:5.56%;border:solid windowtext 1.0pt;border-left: | + | <td width="7%" style="width:7.42%;border:solid windowtext 1.0pt;border-left: |
| none;mso-border-left-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt; | | none;mso-border-left-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt; |
− | background:#FFF2CC;mso-background-themecolor:accent4;mso-background-themetint: | + | padding:0cm 5.4pt 0cm 5.4pt;height:16.25pt"> |
− | 51;padding:0cm 5.4pt 0cm 5.4pt;height:16.25pt">
| + | <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:15.0pt;font-family:Quicksand">Y/N</span><span lang="EN-AU" style="font-size:11.0pt;font-family:Quicksand"><o:p></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:15.0pt; | + | |
− | font-family:Quicksand">Y/N</span></b><b style="mso-bidi-font-weight:normal"><span lang="EN-AU" style="font-size:11.0pt;font-family:Quicksand"><o:p></o:p></span></b></p>
| + | |
| </td> | | </td> |
| </tr> | | </tr> |
| <tr style="mso-yfti-irow:1;height:70.1pt"> | | <tr style="mso-yfti-irow:1;height:70.1pt"> |
− | <td width="50%" style="width:50.94%;border:solid windowtext 1.0pt;border-top: | + | <td width="49%" style="width:49.92%;border:solid windowtext 1.0pt;border-top: |
| none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt; | | none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt; |
| padding:0cm 5.4pt 0cm 5.4pt;height:70.1pt"> | | padding:0cm 5.4pt 0cm 5.4pt;height:70.1pt"> |
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| mso-layout-grid-align:none;text-autospace:none"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-bidi-font-family:Times; | | mso-layout-grid-align:none;text-autospace:none"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-bidi-font-family:Times; |
| color:black">A single chain insulin agonist analogue with stricture of B-LM-A | | color:black">A single chain insulin agonist analogue with stricture of B-LM-A |
− | <span class="GramE">wherein</span> B represents an insulin B chain comprising | + | <span class="GramE">wherein</span> B represents an insulin B chain |
− | the sequence R<sub>22</sub>X<sub>25</sub>LCGX<sub>29</sub></span><sub><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-fareast-font-family: | + | comprising the sequence R<sub>22</sub>X<sub>25</sub>LCGX<sub>29</sub></span><sub><span lang="EN-AU" style="font-size:14.0pt;font-family:Helvetica;mso-fareast-font-family: |
| Helvetica;mso-bidi-font-family:Helvetica;color:black">…</span></sub><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-bidi-font-family: | | Helvetica;mso-bidi-font-family:Helvetica;color:black">…</span></sub><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-bidi-font-family: |
| Times;color:black"> <sub> </sub>and A represents an insulin A chain | | Times;color:black"> <sub> </sub>and A represents an insulin A chain |
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| <p class="MsoNormal" align="center" style="text-align:center;mso-pagination:none; | | <p class="MsoNormal" align="center" style="text-align:center;mso-pagination:none; |
| mso-layout-grid-align:none;text-autospace:none"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-bidi-font-family:Times; | | mso-layout-grid-align:none;text-autospace:none"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-bidi-font-family:Times; |
− | color:black">GIVX<sub>4</sub>X<sub>5</sub>CCX<sub>8</sub></span><sub><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-fareast-font-family: | + | color:black">GIVX<sub>4</sub>X<sub>5</sub>CCX<sub>8</sub></span><sub><span lang="EN-AU" style="font-size:14.0pt;font-family:Helvetica;mso-fareast-font-family: |
| Helvetica;mso-bidi-font-family:Helvetica;color:black">…</span></sub><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-bidi-font-family: | | Helvetica;mso-bidi-font-family:Helvetica;color:black">…</span></sub><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-bidi-font-family: |
| Times;color:black">-R<sub>13</sub> <br style="mso-special-character:line-break"> | | Times;color:black">-R<sub>13</sub> <br style="mso-special-character:line-break"> |
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| <!--[endif]--><o:p></o:p></span></p> | | <!--[endif]--><o:p></o:p></span></p> |
| </td> | | </td> |
− | <td width="43%" style="width:43.5%;border-top:none;border-left:none; | + | <td width="42%" style="width:42.66%;border-top:none;border-left:none; |
| border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; | | 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-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt; |
Line 311: |
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| color:black"><o:p> </o:p></span></p> | | color:black"><o:p> </o:p></span></p> |
| </td> | | </td> |
− | <td width="5%" style="width:5.56%;border-top:none;border-left:none; | + | <td width="7%" style="width:7.42%;border-top:none;border-left:none; |
| border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; | | 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-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; | + | mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt;height:70.1pt"> |
− | height:70.1pt">
| + | <p class="MsoNormal" align="center" style="text-align:center;mso-pagination:none; |
| + | mso-layout-grid-align:none;text-autospace:none"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-bidi-font-family:Times; |
| + | color:black"><o:p> </o:p></span></p> |
| + | <p class="MsoNormal" align="center" style="text-align:center;mso-pagination:none; |
| + | mso-layout-grid-align:none;text-autospace:none"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-bidi-font-family:Times; |
| + | color:black"><o:p> </o:p></span></p> |
| + | <p class="MsoNormal" align="center" style="text-align:center;mso-pagination:none; |
| + | mso-layout-grid-align:none;text-autospace:none"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-bidi-font-family:Times; |
| + | color:black"><o:p> </o:p></span></p> |
| <p class="MsoNormal" align="center" style="text-align:center;mso-pagination:none; | | <p class="MsoNormal" align="center" style="text-align:center;mso-pagination:none; |
| mso-layout-grid-align:none;text-autospace:none"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-bidi-font-family:Times; | | mso-layout-grid-align:none;text-autospace:none"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-bidi-font-family:Times; |
| color:black">N<o:p></o:p></span></p> | | color:black">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;mso-bidi-font-family:Times"><o:p> </o:p></span></p>
| |
| </td> | | </td> |
| </tr> | | </tr> |
| <tr style="mso-yfti-irow:2;height:36.55pt"> | | <tr style="mso-yfti-irow:2;height:36.55pt"> |
− | <td width="50%" style="width:50.94%;border:solid windowtext 1.0pt;border-top: | + | <td width="49%" style="width:49.92%;border:solid windowtext 1.0pt;border-top: |
| none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt; | | none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt; |
| padding:0cm 5.4pt 0cm 5.4pt;height:36.55pt"> | | padding:0cm 5.4pt 0cm 5.4pt;height:36.55pt"> |
Line 358: |
Line 353: |
| color:black"><o:p> </o:p></span></p> | | color:black"><o:p> </o:p></span></p> |
| </td> | | </td> |
− | <td width="43%" style="width:43.5%;border-top:none;border-left:none; | + | <td width="42%" style="width:42.66%;border-top:none;border-left:none; |
| border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; | | 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-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt; |
Line 391: |
Line 386: |
| mso-layout-grid-align:none;text-autospace:none"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-bidi-font-family:Times; | | mso-layout-grid-align:none;text-autospace:none"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-bidi-font-family:Times; |
| color:black">B-chain </span><span lang="EN-AU" style="font-size:14.0pt; | | color:black">B-chain </span><span lang="EN-AU" style="font-size:14.0pt; |
− | font-family:Quicksand;mso-fareast-font-family:Helvetica;mso-bidi-font-family: | + | font-family:Helvetica;mso-fareast-font-family:Helvetica;mso-bidi-font-family: |
| Helvetica;color:black">–</span><span lang="EN-AU" style="font-size:14.0pt; | | Helvetica;color:black">–</span><span lang="EN-AU" style="font-size:14.0pt; |
− | font-family:Quicksand;mso-bidi-font-family:Times;color:black"> QR . . . RR </span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-fareast-font-family: | + | font-family:Quicksand;mso-bidi-font-family:Times;color:black"> QR . . . RR </span><span lang="EN-AU" style="font-size:14.0pt;font-family:Helvetica;mso-fareast-font-family: |
| Helvetica;mso-bidi-font-family:Helvetica;color:black">–</span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-bidi-font-family: | | Helvetica;mso-bidi-font-family:Helvetica;color:black">–</span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-bidi-font-family: |
| Times;color:black"> A-chain</span><span lang="EN-AU" style="font-size:14.0pt; | | Times;color:black"> A-chain</span><span lang="EN-AU" style="font-size:14.0pt; |
− | font-family:Quicksand;mso-fareast-font-family:Helvetica;mso-bidi-font-family: | + | font-family:Helvetica;mso-fareast-font-family:Helvetica;mso-bidi-font-family: |
| Helvetica;color:black"><o:p></o:p></span></p> | | Helvetica;color:black"><o:p></o:p></span></p> |
| </td> | | </td> |
− | <td width="5%" style="width:5.56%;border-top:none;border-left:none; | + | <td width="7%" style="width:7.42%;border-top:none;border-left:none; |
| border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; | | 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-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; | + | mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt;height:36.55pt"> |
− | height:36.55pt">
| + | <p class="MsoNormal" align="center" style="text-align:center;mso-pagination:none; |
| + | mso-layout-grid-align:none;text-autospace:none"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-bidi-font-family:Times; |
| + | color:black;mso-bidi-font-style:italic"><o:p> </o:p></span></p> |
| + | <p class="MsoNormal" align="center" style="text-align:center;mso-pagination:none; |
| + | mso-layout-grid-align:none;text-autospace:none"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-bidi-font-family:Times; |
| + | color:black;mso-bidi-font-style:italic"><o:p> </o:p></span></p> |
| + | <p class="MsoNormal" align="center" style="text-align:center;mso-pagination:none; |
| + | mso-layout-grid-align:none;text-autospace:none"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-bidi-font-family:Times; |
| + | color:black;mso-bidi-font-style:italic"><o:p> </o:p></span></p> |
| + | <p class="MsoNormal" align="center" style="text-align:center;mso-pagination:none; |
| + | mso-layout-grid-align:none;text-autospace:none"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-bidi-font-family:Times; |
| + | color:black;mso-bidi-font-style:italic"><o:p> </o:p></span></p> |
| + | <p class="MsoNormal" align="center" style="text-align:center;mso-pagination:none; |
| + | mso-layout-grid-align:none;text-autospace:none"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-bidi-font-family:Times; |
| + | color:black;mso-bidi-font-style:italic"><o:p> </o:p></span></p> |
| <p class="MsoNormal" align="center" style="text-align:center;mso-pagination:none; | | <p class="MsoNormal" align="center" style="text-align:center;mso-pagination:none; |
| mso-layout-grid-align:none;text-autospace:none"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-bidi-font-family:Times; | | mso-layout-grid-align:none;text-autospace:none"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-bidi-font-family:Times; |
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| </tr> | | </tr> |
| <tr style="mso-yfti-irow:3;height:52.55pt"> | | <tr style="mso-yfti-irow:3;height:52.55pt"> |
− | <td width="50%" style="width:50.94%;border:solid windowtext 1.0pt;border-top: | + | <td width="49%" style="width:49.92%;border:solid windowtext 1.0pt;border-top: |
| none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt; | | none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt; |
| padding:0cm 5.4pt 0cm 5.4pt;height:52.55pt"> | | padding:0cm 5.4pt 0cm 5.4pt;height:52.55pt"> |
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| color:black"><o:p> </o:p></span></p> | | color:black"><o:p> </o:p></span></p> |
| </td> | | </td> |
− | <td width="43%" style="width:43.5%;border-top:none;border-left:none; | + | <td width="42%" style="width:42.66%;border-top:none;border-left:none; |
| border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; | | 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-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt; |
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| amino acids.<o:p></o:p></span></p> | | amino acids.<o:p></o:p></span></p> |
| </td> | | </td> |
− | <td width="5%" style="width:5.56%;border-top:none;border-left:none; | + | <td width="7%" style="width:7.42%;border-top:none;border-left:none; |
| border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; | | 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-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; | + | mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt;height:52.55pt"> |
− | height:52.55pt">
| + | |
| <p class="MsoNormal" align="center" style="text-align:center;mso-pagination:none; | | <p class="MsoNormal" align="center" style="text-align:center;mso-pagination:none; |
| mso-layout-grid-align:none;text-autospace:none"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-bidi-font-family:Times; | | mso-layout-grid-align:none;text-autospace:none"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-bidi-font-family:Times; |
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| </tr> | | </tr> |
| <tr style="mso-yfti-irow:4;mso-yfti-lastrow:yes;height:16.25pt"> | | <tr style="mso-yfti-irow:4;mso-yfti-lastrow:yes;height:16.25pt"> |
− | <td width="50%" style="width:50.94%;border:solid windowtext 1.0pt;border-top: | + | <td width="49%" style="width:49.92%;border:solid windowtext 1.0pt;border-top: |
| none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt; | | none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt; |
| padding:0cm 5.4pt 0cm 5.4pt;height:16.25pt"> | | padding:0cm 5.4pt 0cm 5.4pt;height:16.25pt"> |
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| color:black">LM represents linking moiety linking the carboxyl terminus of | | color:black">LM represents linking moiety linking the carboxyl terminus of |
| the B chain to the amino terminus of <span class="GramE">the a</span> chain, | | the B chain to the amino terminus of <span class="GramE">the a</span> chain, |
− | wherein said linking moiety is an <span style="mso-bidi-font-weight:bold">8 | + | wherein said linking moiety is an <span style="mso-bidi-font-weight:bold">8 amino |
− | amino acid sequence</span> consisting of X<sub>51</sub>X<sub>52</sub>X<sub>53</sub>X<sub>54</sub>... | + | acid sequence</span> consisting of X<sub>51</sub>X<sub>52</sub>X<sub>53</sub>X<sub>54</sub>... |
| wherein X<sub>51</sub></span><span lang="EN-AU" style="font-size:14.0pt; | | wherein X<sub>51</sub></span><span lang="EN-AU" style="font-size:14.0pt; |
− | font-family:Quicksand;mso-fareast-font-family:Helvetica;mso-bidi-font-family: | + | font-family:Helvetica;mso-fareast-font-family:Helvetica;mso-bidi-font-family: |
| Helvetica;color:black"> </span><span lang="EN-AU" style="font-size:14.0pt; | | Helvetica;color:black"> </span><span lang="EN-AU" style="font-size:14.0pt; |
| font-family:Quicksand;mso-bidi-font-family:Times;color:black">is selected | | font-family:Quicksand;mso-bidi-font-family:Times;color:black">is selected |
| from the group consisting of glycine, alanine, valine, leucine, isoleucine | | from the group consisting of glycine, alanine, valine, leucine, isoleucine |
− | and proline</span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand; | + | and proline</span><span lang="EN-AU" style="font-size:14.0pt;font-family:Helvetica; |
| mso-fareast-font-family:Helvetica;mso-bidi-font-family:Helvetica;color:black">…</span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-bidi-font-family: | | mso-fareast-font-family:Helvetica;mso-bidi-font-family:Helvetica;color:black">…</span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-bidi-font-family: |
| Times;color:black"><o:p></o:p></span></p> | | Times;color:black"><o:p></o:p></span></p> |
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| color:black"><o:p> </o:p></span></p> | | color:black"><o:p> </o:p></span></p> |
| </td> | | </td> |
− | <td width="43%" style="width:43.5%;border-top:none;border-left:none; | + | <td width="42%" style="width:42.66%;border-top:none;border-left:none; |
| border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; | | 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-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt; |
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| orientation) and outside the scope<o:p></o:p></span></p> | | orientation) and outside the scope<o:p></o:p></span></p> |
| </td> | | </td> |
− | <td width="5%" style="width:5.56%;border-top:none;border-left:none; | + | <td width="7%" style="width:7.42%;border-top:none;border-left:none; |
| border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; | | 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-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; | + | mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt;height:16.25pt"> |
− | height:16.25pt">
| + | |
| <p class="MsoNormal" align="center" style="text-align:center;mso-pagination:none; | | <p class="MsoNormal" align="center" style="text-align:center;mso-pagination:none; |
| mso-layout-grid-align:none;text-autospace:none"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-bidi-font-family:Times; | | mso-layout-grid-align:none;text-autospace:none"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-bidi-font-family:Times; |
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| | | |
| | | |
− | </div> | + | </div> |
| <div class="patent_1 box"> | | <div class="patent_1 box"> |
− | <p class="MsoNormal" align="center" style="text-align:center"><b style="mso-bidi-font-weight:
| + | <table width="709"> |
− | normal"><span lang="EN-AU" style="font-size:20.0pt;font-family:Quicksand">LEE ET
| + | <tbody> |
− | AL.<o:p></o:p></span></b></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">Single Chain Insulin Analog and
| + | <p><strong>Claims</strong></p> |
− | a polynucleotide sequence encoding the <span class="SpellE">analog</span><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-size:16.0pt;font-family:Quicksand">Patent No: <b style="mso-bidi-font-weight:
| + | <p><strong>Comparison with our sequence</strong></p> |
− | normal">US 6,630,348 B1<o:p></o:p></b></span></p>
| + | </td> |
− | | + | <td width="52"> |
− | <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><strong>Y/N</strong></p> |
− | 2003<o:p></o:p></span></p>
| + | </td> |
− | | + | </tr> |
− | <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-family:Quicksand"><o:p> </o:p></span></p>
| + | <tr> |
− | | + | <td width="354"> |
− | <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; | + | <p> A single chain insulin agonist analogue with stricture of B-LM-A wherein B represents an insulin B chain comprising the sequence R<sub>22</sub>X<sub>25</sub>LCGX<sub>29…</sub> <sub> </sub>and A represents an insulin A chain comprising the sequence GIVX<sub>4</sub>X<sub>5</sub>CCX<sub>8…</sub>-R<sub>13</sub> </p> |
− | mso-yfti-tbllook:1184;mso-padding-alt:0cm 5.4pt 0cm 5.4pt">
| + | </td> |
− | <tbody><tr style="mso-yfti-irow:0;mso-yfti-firstrow:yes;height:53.95pt">
| + | <td width="302"> |
− | <td width="50%" style="width:50.6%;border:solid windowtext 1.0pt;mso-border-alt:
| + | <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> |
− | solid windowtext .5pt;background:#A1C4C8;padding:0cm 5.4pt 0cm 5.4pt;
| + | </td> |
− | height:53.95pt">
| + | <td width="52"> |
− | <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>N</p> |
− | font-family:Quicksand"><o:p> </o:p></span></b></p>
| + | </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;
| + | </tr> |
− | font-family:Quicksand">CLAIM<br style="mso-special-character:line-break">
| + | <tr> |
− | <!--[if !supportLineBreakNewLine]--><br style="mso-special-character:line-break">
| + | <td width="354"> |
− | <!--[endif]--><o:p></o:p></span></b></p>
| + | <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> |
− | </td>
| + | <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> |
− | <td width="43%" style="width:43.1%;border:solid windowtext 1.0pt;border-left:
| + | </td> |
− | none;mso-border-left-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
| + | <td width="302"> |
− | background:#A1C4C8;padding:0cm 5.4pt 0cm 5.4pt;height:53.95pt">
| + | <p><em>Our amino acid sequence is squarely outside the scope of 8 amino acids.</em></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;
| + | <p> </p> |
− | font-family:Quicksand"><br>
| + | <p>Even if we did fall within the claim; we do not contain the 8 amino acid sequence using both potential orientations</p> |
− | COMPARISON WITH OUR SEQUENCE<br style="mso-special-character:line-break">
| + | <p>X<sub>51</sub> is glutamine or arganine in our sequence</p> |
− | <!--[if !supportLineBreakNewLine]--><br style="mso-special-character:line-break">
| + | <p> B-chain - QR…..RR – A-chain</p> |
− | <!--[endif]--><o:p></o:p></span></b></p>
| + | </td> |
− | </td>
| + | <td width="52"> |
− | <td width="6%" style="width:6.3%;border:solid windowtext 1.0pt;border-left:
| + | <p>N</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">
| + | </tr> |
− | <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;
| + | <tr> |
− | font-family:Quicksand">Y/N<o:p></o:p></span></b></p>
| + | <td width="354"> |
− | </td>
| + | <p>The LM also requires the sequence of GAGSSSRR or a sequence that differs from GAGSSRR by 1 or 2 amino acids</p> |
− | </tr>
| + | </td> |
− | <tr style="mso-yfti-irow:1">
| + | <td width="302"> |
− | <td width="50%" style="width:50.6%;border:solid windowtext 1.0pt;border-top:
| + | <p>Our sequence is 12 amino acids long and differs by more than 4 amino acids.</p> |
− | none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt;
| + | </td> |
− | padding:0cm 5.4pt 0cm 5.4pt">
| + | <td width="52"> |
− | <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p> </o:p></span></p>
| + | <p>N</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
| + | </tr> |
− | binding activity than proinsulin and less insulin receptor binding activity
| + | <tr> |
− | than insulin:<br style="mso-special-character:line-break">
| + | <td width="354"> |
− | <!--[if !supportLineBreakNewLine]--><br style="mso-special-character:line-break">
| + | <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>… wherein X<sub>51</sub> is selected from the group consisting of glycine, alanine, valine, leucine, isoleucine and proline…</p> |
− | <!--[endif]--><o:p></o:p></span></p>
| + | </td> |
− | <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand">B chain -<span style="mso-spacerun:yes"> </span>X </span><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand;mso-fareast-font-family:Helvetica;
| + | <td width="302"> |
− | mso-bidi-font-family:Helvetica">–</span><span lang="EN-AU" style="font-size:
| + | <p> Similarly, the patent claim is over a 8 amino acid sequence. Applying the same principle our<br /> </p> |
− | 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;
| + | <p>X<sub>51</sub> is glutamine or arginine (depending on orientation) and outside the scope </p> |
− | mso-bidi-font-family:Helvetica"><o:p></o:p></span></p>
| + | </td> |
− | <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;
| + | <td width="52"> |
− | mso-bidi-font-family:Helvetica"><o:p> </o:p></span></p>
| + | <p>N</p> |
− | </td>
| + | </td> |
− | <td width="43%" style="width:43.1%;border-top:none;border-left:none;
| + | </tr> |
− | border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
| + | </tbody> |
− | mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt;
| + | </table> |
− | mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt">
| + | </div> |
− | <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:
| + | <div class="patent_2 box">2nd patent shit</div> |
− | 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:
| + | <div class="patent_3 box">3rd patent shite</div> |
− | 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> </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> </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> </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> </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> </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> </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> </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"><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> </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> </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> </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> </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> </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> </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> </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> </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> </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> </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> </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> </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> </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> </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> </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> </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> </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> </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> </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> </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> </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> </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> </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"><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> </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> </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> 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> 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> 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> </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> </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> </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> 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> (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> </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"> 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> </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"> 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> </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"> 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> </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"> 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"> 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> </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"> 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> </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"> 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"><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 <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> </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> </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> </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> </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> </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> </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> </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> </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> </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> </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> </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> </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> </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> </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> </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> </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> </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> </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> </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> </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> </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> </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"><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> </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> </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> </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> </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> </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> </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> </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> </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> </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> </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> </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> </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> </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> </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> </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> </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> </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> </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> </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>
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− | <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p> </o:p></span></p>
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− | <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>
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− | <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;font-family:Quicksand"><o:p> </o:p></span></p>
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− | </td>
| + | |
− | <td width="45%" style="width:45.14%;border-top:none;border-left:none;
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− | 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> </o:p></span></p>
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− | <p class="MsoNormal" align="center" style="text-align:center"><span lang="EN-AU" style="font-size:14.0pt;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:14.0pt;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:14.0pt;font-family:Quicksand"><o:p> </o:p></span></p>
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− | <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;
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− | border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;
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− | 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>
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