definiens: means Program Patents Controlled by a Party or an y of its Affiliates on the Effective Date or during the Agreement Term claimin g ( a ) methods of dosing ( frequency, duration, conce ntration, volume, etc . ) generally applicable to Oligonucleoti des to achieve optimal tissue distribution or enhan ce other properties of an Oligonucleotide ; ( b ) methods of de termining an effective human dose based on animal d ata that are generally applicable to Oligonucleotides ; ( c ) m ethods of determining an effective dose based on ac tual or modeled pharmacokinetic data generally applicable t o Oligonucleotides ; ( d ) methods of identifying or o ptimizing predictive biomarkers for diseases ; ( e ) observation s about a disease based on data from a natural hist ory study ; ( f ) proprietary disease models ; or ( g ) methods of using radio - labeled ligands with Oligonucleotides in ani mals