May 11, 2023
On May 2, 2023, the Patent Trial and Appeal Board (PTAB) reversed the Examiner’s rejection of a claim directed to a method of creating an immobilized DNA library while preserving contiguity information of a target nucleic acid as being both anticipated and obvious (Appeal 2023-000053). Claim 1 of the application US 15/519,482 (the ‘482 Application) is directed towards:
Claim 1. A method of preparing a library of barcoded DNA fragments of a target DNA comprising:
a. binding a target DNA to a plurality of transposome complexes, each transposome complex comprising transposons and transposases, wherein the transposons comprise transferred strands and non-transferred strands, and wherein at least one of the transposons of the transposome complex comprises an adaptor sequence capable of hybridizing to a complementary capture sequence;
b. fragmenting the target DNA of step (a) into a plurality of contiguously-linked, transposed DNA fragments and inserting a plurality of transferred strands into at least one strand of each contiguously-linked transposed DNA fragment of the plurality of contiguously-linked transposed fragments, wherein contiguity of DNA fragments of the target DNA is maintained by the transposases;
c. immobilizing the plurality of contiguously-linked, transposed DNA fragments of step (b) on a plurality of solid supports by hybridizing the adaptor sequence of the at least one of the transposons to a complementary capture sequence, each of the solid supports in the plurality comprising a plurality of immobilized oligonucleotides, each oligonucleotide of the plurality of immobilized oligonucleotides comprising, in sequential order extending from a surface of the solid support:
i. a first primer binding site attached to the solid support;
ii. a first barcode sequence; and
iii. a complementary capture sequence capable of hybridizing to the adaptor sequence; and
d. attaching the first barcode sequence to one or more of the plurality of contiguously-linked, transposed DNA fragments of step (c), thereby producing a library of barcoded, linked DNA fragments,
wherein the first barcode sequences of all of the oligonucleotides of the plurality of oligonucleotides immobilized on a given solid support comprise the same nucleic acid sequence,
wherein a nucleic acid sequence of the first barcode sequence of the oligonucleotides of the plurality of oligonucleotides immobilized on a given solid support in the plurality of the solid supports differs from a nucleic acid sequence of all of the first barcode sequences from other solid supports in the plurality of solid supports, and
wherein the steps (a)-(d) are carried out in a single reaction compartment.
The Examiner determined the claimed method was anticipated by Shendure et al., US 2013/0203605 (Shendure), stating Shendure teaches steps (a) through (d) encompassed in claim 1. Appellant argued that the claimed method could not be anticipated because “steps (a) through (d) carried out in a single reaction compartment” was not disclosed in Shendure (Appeal Decision p. 10).
The PTAB centered its analysis of the case on whether the Examiner’s interpretation of a “single reaction compartment” was reasonable within light of the specification. During prosecution, the Examiner interpreted a “single reaction compartment” to mean “any ‘single reaction compartment’ (e.g., . . . a laboratory . . . an emulsion . . . etc.)” (Appeal Decision p. 10). The Examiner supported this broad interpretation stating that because claim 1 did not recite a specific example or limitations to a “single reaction compartment,” the phrase could be interpreted to mean any compartment where a reaction may occur such as ‘“the earth’ ‘the ocean’ or ‘a laboratory’” (Appeal Decision p. 12). Appellant argued the Examiner’s interpretation of a “single reaction compartment” was improper because it was interpreted too broadly and without consideration of the ‘482 Application’s specification.
The PTAB agreed with the Appellant, stating that while the specification did not provide a separate definition for “single reaction compartment,” the specification did not allow the Examiner to interpret a “single reaction compartment” to be as broad as ‘“the earth’ ‘the ocean’ or ‘a laboratory’” (Appeal Decision p. 12). Although the specification did not include an individual definition for a “single reaction compartment”, it described that “the index beads can be pooled, target nucleic acid can be added to the pool, tagmented and subsequent PCR amplification may be performed in a single reaction compartment (‘one-pot’)” (Appeal Decision p. 12). The specification further described “[c]apturing contiguously-linked, transposed, target nucleic acid onto a solid support through hybridization” (Appeal Decision p. 12). The PTAB reasoned that because the capture of nucleic acid is based on hybridization and not transportation, there was an increased chance a single target DNA would wrap around an indexed bead. Because of this, tagmentation and PCR amplification may occur within a single reaction compartment reaction “eliminating the need to carryout individual reactions for each index sequences” (Appeal Decision p. 12). Based on these descriptions, the PTAB interpreted a “single reaction compartment” as a test tube or a well on a plate, and not reactions occurring in ‘“the earth’ ‘the ocean’ or ‘a laboratory’” (Appeal Decision p. 12). The PTAB concluded that the Examiner had interpreted the term too broadly, without consideration of the specification, thus leading to an improper conclusion that the claimed invention was anticipated by Shendure (Appeal Decision p. 14).As in the case of the ‘482 Application, the broadest reasonable interpretation of a claim does not equate to the broadest possible interpretation. Examiners are directed to interpret the claims in light of the ordinary and customary meaning given to the terms, unless a term is given a different meaning within the specification. This decision serves as a reminder for practitioners to use the specification as a lexicon should there be a term used outside of the ordinary and customary meaning. Practitioners should also remember to ensure that terms are used consistently and are well-developed within the specification, to support the term’s meaning within the specification. During examination, practitioners should also pay attention to whether the Examiner has defined terms properly and in line with the specification when responding to rejections.