1 Homology Language Brian R. Stanton Quality Assurance Specialist Technology Center 1600 U.S. Patent and Trademark Office (703) Biotechnology/Chemistry/Pharmaceutical Customer Partnership U.S. Patent and Trademark Office Arlington, Va July 29, 2003

2 Language % identical Homology, identity, similarity Hybridization

3 Sample Claims An isolated and purified nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 1. An isolated and purified nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 1 wherein said nucleic acid encodes a protein having activity X.

4 Sample Claims An isolated and purified nucleic acid comprising a nucleotide sequence that is 90% identical to SEQ ID NO: 1. An isolated and purified nucleic acid comprising a nucleotide sequence that is 90% identical to SEQ ID NO: 1, wherein said nucleic acid encodes a protein having activity X. The specification provides sufficient support that isolated protein has a specific, substantial, and credible use related to activity X.

5 Written Description An isolated and purified nucleic acid comprising a nucleotide sequence that is 90% identical to SEQ ID NO: 1. An isolated and purified nucleic acid comprising a nucleotide sequence that is 90% identical to SEQ ID NO: 1, wherein said nucleic acid encodes a protein having activity X.

6 Functional language If the specification provides sufficient support that the isolated protein has a specific, substantial, and credible use related to activity X, limiting the claims to proteins having activity X may help resolve a scope of enablement issue.

7 Enablement How to make? How to find?

8 Scope of enablement (some considerations) Consensus sequences State of the Art Specification Support Alignments? Critical Residues What to change and what not to change Variations What substitutions, deletions, insertions may be made? Where can changes be made?

9 Enablement: Claim language (some considerations) Consensus sequence in claim? Critical residues in claim? e.g. An isolated and purified nucleic acid comprising a nucleotide sequences that is 90% identical to SEQ ID NO: 1, wherein said nucleic acid encodes a protein having activity X, and further wherein said nucleic acid includes SEQ ID NO: 2. SEQ ID NO: 2 is the nucleotide sequence that encodes the catalytic domain (SEQ ID NO: 3) of a protein having activity X. SEQ ID NO: 3 is sufficient to endow a protein with catalytic activity X.

10 What % homology is appropriate? Distinguish over prior art Technology based Do alignments yield information that suggests an appropriate amount of variation?

11 Consensus Sequence Example A G C T T C C G G C T T A T A A A C G T A C T A T C C A G T A T A A A T A C T T Consensus A x x x T C C x G x x T A x A x A C x T 11/20 = 55% homology between the two molecules. Do they both have the desired function? Are there teachings re: the permitted changes for the degenerate positions? What is the homology at the amino acid level? Are there teachings re: the permitted changes at the amino acid level?

12 Enablement (cont.) Assay How to find? How to screen for operative embodiments? Wands analysis