[Music] foreign we will demonstrate the use of scifinder's sequence search capabilities for cdrs cdrs are complementary determining regions that are part of antibodies we see here the growing application of antibody drug conjugates in the patent literature in scifinder very often these patterns Define antibody drug conjugates as three different components one being the antibody the Linker and the U in this case represents the cytotoxic molecule if we look at the earlier part of the patent we would see that the cdrs have been identified as sequences we can use file finders sequence search capabilities to determine if
there are similar definitions in patterns of antibodies and their cdrs to retrieve possible prior hearts for that we will log into site finder go to the sequence button and here we have three options for blast CDR Motif we will use the CDR pdrs are short stretches of amino acids which are highly variable they're responsible for the binding regions of an antibody and each chain of an antibody or T Cell receptor has three cdrs so that's why we have three search boxes for them the CDR search searches in a part of the database where sequences have
been identified either as antibodies or T cell receptors let's bring these three cdrs into our search box so after entering the three cdrs we can decide to include also sequences from The ncbi Source or start the sequence search sequence search will run here and we see that the search has been completed very quickly and open up the results the sequence search and SCI finder brings back a hundred thousand results that are visualized in this Venn diagram for those sequences that include all three or only two or just a single CDR in the antibody or T
Cell receptor that was created we will focus on those that have all CDR components we now retrieve 11 results that can be sorted either by alignment e-value query coverage or subject coverage here we see where the three cdrs have matched either a light chain or heavy chain part of an antibody we see the alignment which is a hundred percent we can check that up here in the tab for subject we will see the total definition of the antibody we can see this is a synthetic construct there are also several registry numbers for these sequences in
the reference tab we'll find the latest patterns as well as Journal articles for this particular answer we can get to the references just for this sequence by clicking this reference button further down we will also see that there are answers where where the sequence did not have a hundred percent alignment identity here we see that other amino acids um have been reported in the subject but still close answers like these can be retrieved quite easily they would have their own specific patent and possible non-patent literature references we go further back to the top we do
have some additional filtering capability particular for sequence lengths here we do see that the length is in a Range that would actually match the light chain component of an antibody but we could if we want a filter by that could also indicate that the alignment would have to be higher than the 90 that we potentially want otherwise we can also look for all of the patent references for all 11 answers by clicking the reference button here at the top this will export all of the patent numbers retrieved for all 11 sequences and group them by
family and report them back into the site finder interface we see that the 11 answers were retrieved in 25 patent families in order to combine the CDR sequence result with a structure search for the toxin we can save this answer for later use we click here at the top right on the save button give it a name save it and now we are ready to start the second part of our search which will Define the toxin go back to the landing page of scifinder go to substances and here I would be interested in finding derivatives
of specific toxin called mmae can see that there's a variety of names available we'll search for it we see that we do retrieve the compound itself I'll click on the structure click on edit structure to put it into the structure editor make that a little bit larger and in order to retrieve also further variations I'm going to remove these two substituents and leave them open for any type of substitution at that particular point can if you prefer to also flatten the stereochemistry of the toxin for a more complete retrieval click on OK and run the
structure search for the structure search we see that there are two exact match but we are more interested in the 5500 substructure search answers where potentially additional linkers could be defined to connect the mmae or other derivatives to the antibody so we have now completed our structure search with several variations that could could exist here would look for the references for these substances finding almost 3 000 references including a good number of of patterns here we're going to use the Venn diagram icon to do a combination with our previously saved answer set we'll use intersect
select the 25 patterns we retrieved from the CDR search and simply click on view results we now retrieve Five results that have the combination of our CDR for the antibody as well as the small molecule or its variation that we desired we see that we got fairly recent patterns and if we look at the organizations we see that ramagen as well as cgen are the two companies competing in this particular area [Music] thank you
