Status of the Claims
Claims 1, 7-15, 17-22, and 29-31 are pending and examined herein.
Claims 1, 7-8, 13-15, 17-22, and 29 are amended.
Claims 6 and 16 are canceled.
Claim 31 is newly added.
The following Office Action is in response to Applicant’s communication dated 08/05/2026. Rejection(s) and/or objection(s) not reiterated from previous office actions are hereby withdrawn. The following rejection(s) and/or objection(s) are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. Specifically, the rejection of claims 18 and 19 under 35 § USC 112(b) are withdrawn in light of Applicant’s amendments. The rejections of claims 6, 8-12, 16, 18, and 20-21 under 35 USC § 102(a)(1) over Jelinek et al., claims 1, 13-15, 21, and 29 under 35 USC § 102(a)(1) over Gloeckner et al., and claims 1, 7-9, 13, 20-21, and 29-30 under 35 USC § 102(a)(1) over Carter et al. are similarly withdrawn.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Modified Claim Rejections - 35 USC § 102
Necessitated by Amendments
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Jelinek et al.
Claims 1, 7, 13, 22, and 29 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jelinek et al. (US PGPub No: US2016/0115474).
Regarding claims 1 and 22, Jelinek discloses a method (Fig. 1B; claims 2 and 10) comprising providing a sample of genomic DNA and adding an engineered transposome complex (p. 2, ¶[0017]) that comprises an oligonucleotide and an engineered transposase (p. 2, ¶[0017]: “protein-oligonucleotide conjugate”), wherein the engineered transposase comprises a transposase operably (p. 8, ¶[0095-6]) linked to a polypeptide that does not comprise an antibody or antibody binding domain (p. 2, ¶[0023], lines 7-14; p. 6, ¶[0078]: “transcription factors or chromodomains”; p. 8, ¶[0099]).
Additionally, Jelinek discloses adding at least one further transposome complex. As there is no recited requirement in the instant claim for the at least one engineered transposome complex and the at least one further transposome complex to comprise different oligonucleotides or polypeptides, multiple copies of the same transposome complex fall within the broadest reasonable interpretation of the claim. As the method of Jelinek does not disclose single molecule methods, it would be clear to one of ordinary skill in the art that multiple copies of the transposome complex of Jelinek are used in the disclosed method, thereby anticipating the instant claim.
Regarding claim 7, Jelinek further discloses that the oligonucleotide comprises a 5’-phosphate group (Fig. 18).
Regarding claim 13, Jelinek further discloses that the transposase is Tn5 (p. 3, ¶[0025]).
Regarding claim 29, Jelinek further discloses that the method comprises sequencing tagged DNA (p. 17, ¶[0169-70]).
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Response to Arguments
Applicant's arguments filed 08/05/2026 regarding claims 1 and 22 have been fully considered but they are not persuasive for the following reasons. Applicant contends that Jelinek does not disclose an embodiment where one of the transposome complexes does not comprise an antibody or antibody binding domain and at least one further complex is present on page 9. The Examiner contends that this issue has been adequately addressed in the above section, which is incorporated in its entirety herein by reference. Applicant further argues that Jelinek does not disclose a working example of a transposome complex as recited in claims 1 or 22 on pages 11-13. However, a working example is not required for a reference to anticipate an invention. As stated in MPEP § 2123, “A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art”. Jelinek clearly discloses a transposome complex comprising a transposase conjugated to a protein that is not an antibody, as demonstrated above. Lastly, on pages 12-13, applicant argues that Jelinek does not disclose or suggest a method for simultaneously probing open and closed chromatin. In response to applicant's argument that the reference fails to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., probing open and closed chromatin; multiplexing) are not recited in the rejected claims. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
New and Modified Claim Rejections - 35 USC § 103
Necessitated by Amendment
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Jelinek et al.
Claims 14-15, 18, 20-21, and 31 are rejected under 35 U.S.C. 103 as being unpatentable over Jelinek et al.
Regarding claim 18, Jelinek discloses the limitations of claim 1 as discussed previously. Additionally, Jelinek further discloses tagging sequences (“barcode sequence”) that differ between transposome complexes (p. 11, ¶[0127]: “each conjugate bearing a unique barcode sequence”). Jelinek does not specifically disclose the use of these barcodes with transposome complexes that are not conjugated to antibodies. However, it is clear from the disclosure of Jelinek that the non-antibody transposome conjugates are used equivalently and therefore it would be obvious to combine the method of claim 1 with the disclosed tagging sequences.
Regarding claims 20-21 and 31, Jelinek further discloses that the polypeptide comprises the chromodomain of heterochromatin protein 1 (p. 6, ¶[0078]: “chromodomains, such as in HP1”). Jelinek does not disclose that the polypeptide comprises, specifically, the chromodomain of HP1-α. However, it would have been obvious to one of ordinary skill in the art by the effective filing date to incorporate the chromodomain of the α paralog as there are a limited number of potential sequences. Specifically, in mammals there are only 3 paralogous HP1 sequences, each of which has a largely conserved chromodomain. Therefore, one of ordinary skill in the art could have pursued these known potential solutions with a reasonable expectation of success.
Regarding claims 14 and 15, a transposase conjugated to the chromodomain of HP1-α is obvious over the disclosure of Jelinek, as discussed above, as would be using said transposase conjugate in the method of claim 1. Jelinek does not disclose that the sequence of the engineered transposase comprises SEQ ID NOs: 9 and 24, nor SEQ ID NO: 3. However, if one of ordinary skill in the art synthesized a transposase by conjugating the chromodomain of HP1-α to Tn5, as suggested by Jelinek, this would result in a sequence that has >90% identity to the sequences of SEQ ID NOs: 3, 9, and 24.
Jelinek et al. and van Galen et al.
Claims 8-12, 17 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Jelinek et al. in view of van Galen et al. (Mol. Cell (2016), 61:170-180).
Regarding claim 17, Jelinek discloses all limitations of claim 1, upon which 17 is dependent, as discussed above. Jelinek also teaches multiple transposome complexes that bind to different methylated histones (p. 8, ¶[0099]: “…would enable binding to H3K9Me3, H3K27me3, H3K27me3, H3K9me3, and H3K36me3”). However, Jelinek does not disclose that these specific engineered transposome complexes are used in the method of claim 1.
Van Galen discloses a method of multiplexed ChIP-seq for profiling histone methylation (Fig. 1). Additionally, van Galen teaches that multiplexing increases the “quantitative consistency” of histone methylation profiling methods (p. 170, col. 2, 1st ¶). Based on the fact that Jelinek discloses multiplexing as well as multiple transposome complexes that bind different methylated histones, one of ordinary skill in the art would have been able to arrive at the invention of claim 17 using the combined disclosures of Jelinek and van Galen, based on the motivation provided by van Galen. Additionally, there would have been a reasonable expectation of success in applying the multiplexed histone methylation profiling of van Galen to the multiplexed TAM-ChIP method of Jelinek, as Jelinek explicitly teaches that the disclosed TAM-ChIP method is an improvement on the standard ChIP methodology, as used in van Galen (P. 6, ¶[0075]).
Therefore, it would have been obvious to one of ordinary skill in the art by the effective filing date to apply the multiplexed histone methylation profiling of van Galen to the multiplexed TAM-ChIP method of Jelinek based on the motivation of increasing the quantitative consistency of TAM-ChIP methylation profiling, with a reasonable expectation of success.
Regarding claim 19, van Galen further discloses comparing the results obtained from the two different methylation profiling methods at a DNA locus (Fig. 1).
Regarding claim 8, van Galen discloses simultaneously targeting heterochromatin and euchromatin (Figure 2C-E; p. 172, Results, 1st ¶: “H3K4me3, H3K27me3, H3K27ac, and total H3”). As discussed with relation to claim 17, it would have been obvious to use the method of Jelinek to achieve the multiplexing of van Galen, and therefore the targets of van Galen would have been obvious targets to investigate via the method of Jelinek. Additionally, there would have been a reasonable expectation of success in doing so as Jelinek discloses normalizing transposition efficiency between heterochromatin and euchromatin (p. 10, ¶[0123]: “transcriptionally active and inactive regions”), indicating that transposition measurements are able to be taken in both of these regions by the disclosed method.
Regarding claims 9-12, it would have been obvious for the polypeptide to comprise the chromodomain of HP1-α, as discussed in relation to claims 20-21 and 31 above. Jelinek teaches that the chromodomain of HP1-α targets H3K9me histones (p. 1, ¶[0003])
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Response to Arguments
Applicant’s arguments filed 08/05/2026 regarding the alleged non-obviousness of claims 1 and 22 on pages 11-13 have been fully considered but they are not persuasive for the reasons discussed in the previous section.
Applicant’s arguments filed 08/05/2026 regarding the alleged non-obviousness of claims 20-21 and 31 on pages 14-16 have been considered but they are not persuasive for the following reasons. Applicant argues that there is no teaching or suggestion for the use of HP1-α as the polypeptide of an engineered transposase. The applied rejection does not rely on a rationale requiring teaching or suggestion, so this argument is considered moot. Applicant further contends that the use of HP1-α yields properties that could not have been predicted by the prior art. In response, the fact that the inventor has recognized an advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
Applicant's arguments filed 08/05/2026 regarding the combination of Jelinek and van Galen on page 14 have been fully considered but they are not persuasive for the following reasons. Applicant argues that one of ordinary skill would not have combined the disclosures of Jelinek and van Galen because van Galen does not utilize transposases. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/ALEXANDRA OLSON/Examiner, Art Unit 1684
/JEREMY C FLINDERS/Primary Examiner, Art Unit 1684
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