Opinion ID: 3173494
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Heading: compiling an accepted sequence set com-

Text: prising the at least one sample sequence in each orientation accepted in step (g); and j. determining the sequence of the nucleic acid sample using the accepted sequence set. Id. col. 45 ll. 24–47, col. 47 ll. 3–30 (emphasis added). Lastly, claims 27 and 28 of the ’630 patent require the use of a “nucleotide analog that discriminates between a INDUS. TECH. RESEARCH INST. v. PAC. BIOSCIENCES 9 base and its modified form” in sequencing. Id. col. 48 ll. 28–33, 45–50. The ’630 patent describes such a compound as a “discriminating analog” that “pairs preferentially with one but not the other of the base and its modified form.” Id. col. 24 ll. 15–19. The ’630 patent also provides examples of “discriminating analogs” that were known in the art. Id. col. 24 l. 42–col. 25 l. 24 (citing U.S. Patent 7,399,614). Those examples are base-linked analogs, meaning that they have bulky groups chemically linked to the base moiety, allowing them to pair preferentially with a base or its modified form during sequencing. Claim 27 is representative of those two claims and reads as follows: 27. A method of determining a sequence of a dou- ble-stranded nucleic acid sample and a posi- tion of at least one modified base in the sequence, comprising: a. locking the forward and reverse strands together to form a circular pair-locked molecule; b. obtaining sequence data of the circular pair-locked molecule via single molecule sequencing, wherein the sequence data comprises sequences of the forward and reverse strands of the circular pair-locked molecule; c. determining the sequence of the double- stranded nucleic acid sample by compar- ing the sequences of the forward and re- verse strands of the circular pair-locked molecule; d. obtaining sequencing data of the circular pair-locked molecule via single molecule sequencing, wherein at least one nucleotide analog that discriminates between a base and its modified form is used to obtain se- 10 INDUSTRIAL TECH. RESEARCH INST. v. PAC. BIOSCIENCES quence data comprising at least one posi- tion wherein the at least one differentially labeled nucleotide analog was incorpo- rated; and e. determining the positions of modified ba- ses in the sequence of the double-stranded nucleic acid sample by comparing the se- quences of the forward and reverse strands. Id. col. 48 ll. 15–37 (emphasis added).