Nucleotide and protein sequences often disclose symbols to represent modified positions or to draw attention to a certain position. One such symbol is the asterisk (*), and while asterisks can represent a plethora of things, they most often indicate the presence of stop codons. This is extremely important from a Sequence Listing preparation standpoint as the incorrect interpretation can result in a rejection from the United States Patent and Trademark Office. Sequence Listing rules are quite specific as to how the aforementioned sequences are to be disclosed. For example, per , "an amino acid sequence that contains internal terminator symbols (e.g., ‘Ter’, ‘*’, ‘.’, etc.) may not be represented as a single amino acid sequence." In other words, if a stop codon is “embedded” in what appears to be a single protein sequence, the sequence be disclosed as one long, contiguous sequence in a Sequence Listing. Each sequence of four or more specifically defined residues must be assigned its own unique SEQ ID NO identifier. This rule also has ramifications on nucleotide sequences when including the coding feature (known as CDS region) in a Sequence Listing. Each separate coding region must be indicated as an individual CDS region. For instance, coding through a stop codon in a nucleotide sequence will result in a rejection even though the protein sequence may continue to be coded. As you’ll recall, the presence of an asterisk does not indicate a stop codon every time. It is, however, the most common interpretation of the symbol, and minus any further definitions, should likely be treated as such in order to interpret the sequence correctly and prevent the issuance of a rejection.

The overriding statement regarding the inclusion of sequences derives from : "Nucleotide and/or amino acid sequences as used in §§ through are interpreted to mean an unbranched sequence of four or more amino acids or an unbranched sequence of ten or more nucleotides…Sequences with fewer than four specifically defined nucleotides or amino acids are specifically excluded from this section. ‘Specifically defined’ means those amino acids other than ‘Xaa’ and those nucleotide bases other than ‘n’…" goes on to provide additional information for nucleotide sequences: "Nucleotides are intended to embrace only those nucleotides that can be represented using symbols set forth in outlines the symbols which correspond to the 5 naturally occurring bases (a, c, t, g and u), as well as the degenerate bases (r, y, m, k, s, w, b, d, h and v) and the universal variable base (n). Additionally, provides more specific information for protein sequences: "Amino acids are those L-amino acids commonly found in naturally occurring proteins and are listed in " Again, lists out the twenty naturally occurring amino acids (A, C, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W and Y), special residue designations (B and Z), and the universal variable amino acid (X). Sounds fairly straight forward, right? Ha! Not so fast. While these rules sound , they are merely a jumping off point for a litany of other rules to follow when preparing compliant Sequence Listings. So, although determining which sequences qualify for inclusion in a Sequence Listing may seem straightforward, keep in mind that it is just the beginning. Below are two examples of common sequence disclosures that require additional interpretation.

Example One:

Example Two: