The number of amino acid residues reported was either the actual count (if available), or for a few products, as indicated
with boldface type, was estimated from the reported molecular weight. For products known to associate as multimers (e.g.,
insulin hexamers), the number of amino acids listed is the number of amino acids in unique sequences. Therefore, for homomultimers,
the number of amino acids reported is simply the number of amino acids in the monomer. For heteromultimers (e.g., heterodimeric
pituitary hormones, such as follitropin), the number of amino acids reported is the sum of the number in each distinct subunit.
In the case of follitropin, for example, the alpha subunit contains 92 amino acid residues, and the beta subunit contains
111 amino acid residues, for a total of 203 amino acid residues.
Table 2b. Biogeneric target products with annual US sales > $20 million
The protein and peptide products meeting our criteria for potential biogeneric targets are presented in Table 2 in ascending
order of the number of amino acids in unique sequences in the product. This order very crudely approximates ascending order
of product complexity.
Table 2c. Biogeneric target products with annual US sales > $20 million
A total of 75 target products were found that met all of the criteria specified, of which 34 had been filed as NDAs and 41
as BLAs. There is substantial overlap in the molecular sizes of the NDA and BLA products: the NDA products ranged in size
from 7 to about 691 amino acids, and the BLA products from 109 to about 2,322 amino acids. About half of the products were
not chemically modified, three were PEGylated, and the rest were glycosylated. These products have been sorted by chemical
modification and filing pathway in Table 3.
Table 3. Breakdown of products by pathway and chemical modification
These results show that target protein products, without major chemical modifications, have been filed by both the NDA and
the BLA pathways. Likewise, glycosylated target products have been filed by both pathways. Although no PEGylated target products
in this final list were filed by the NDA pathway: this pathway does not preclude PEGylated products. Indeed, there are at
least two PEGylated protein products not reported here (due to insufficient sales volume) that have been approved via the
NDA pathway (Pegademase Bovine [Adagen], and Pegvisomant [Somavert]).
Table 4 shows the results from the final list tabulated by source and by filing pathway. Approximately 15 percent of the products
were produced synthetically. These products ranged in size from 7 to 36 amino acids, and all were approved via the NDA route.
The recombinant DNA products accounted for most (about 83 percent) of the total number of products on the final list, and
ranged in size from 29 to about 2,330 amino acids. Many recombinant DNA products were filed via each of the two major pathways.
Only two products were derived from native DNA (i.e., non-recombinant systems). These were 58 and about 295 amino acids in
length, and were both filed as NDAs.
Table 4. Breakdown of products by pathway and source