Until now I have stayed away from the chemistry of the amyloid beta mabs, though I have finally taken a look and in the above post are some of the things that I found notable.
The first highlight from the top figure in the post above is how extremely similar the chemical formulae for the four different mabs were. I had not realized that they were that similar. I had expected that they might even possibly be entirely different molecules.
This turned out to be completely untrue. In the middle figure we have the amino acid sequence for the chain B of gantenrumab (5CSZ_2), and underneath the Chain A of aducan ( 6CO3_1). The amino acid letters that have been highlighted in red are the differences between the two sequences. It is remarkable how few changes there are between the two mabs. Of more interest is that in the bottom half of these sequences there are no differences; presumably this is where the important binding occurs with beta amyloid. On the right I noted what changes were made as one went from gantenerumab to aducan in terms of the functional impact on the amino acid.
Of the 27 amino acids changes, fully 12 were not actually changes at all. These changes would change one hydrophobic amino acid for another hydrophobic amino acid: not really much of a change -- as a first guess such changes might have somewhat subtle effects on the protein. The most consistent change that is noted is the change from a hydrophobic group on gantenerumab to a polar group on aducan. This happened 8 times. This might be no accident as I vaguely recall that abeta mabs with more hydrophobic quality could be helpful in disrupting the amyloid structure. So the order really should have been from aducan --> gantenerumab not the other way round as, the basic scaffold of aducan was likely taken and then tweaked where thought appropriate.
Given the above insights it might be expected that the anti-amyloids that are now near or have achieved approval will likely have similar effects. However, as we are all too aware with e.g. APOE e4, even a single letter substitution can create differing biological effects.
The url below provides a very wide range of annotations for the C chain. Funnily enough acetylcholine function is prominently mentioned.
https://www.rcsb.org/annotations/6CO3