DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Application
2. Applicant’s response filed on March 30, 2026 has been entered.
Claims 1 and 6-17 are pending. Claim 1 is under examination. Claims 6-17 remain withdrawn from consideration as being drawn to a non-elected invention.
Response to Arguments
3. Applicant’s arguments filed on March 30, 2026 have been fully considered.
Objection to the Drawings
Applicant argues that the objection to the drawings should be withdrawn in view of the replacement drawing sheet and amendments to the specification filed with the response (Remarks, page 8).
This argument was persuasive. The objection has been withdrawn.
Objections to the Specification
Applicant argues that the objections should be withdrawn in view of the amendments to the specification and title of the application (Remarks, pages 8-9).
This argument was persuasive. The objections have been withdrawn.
Rejection of claims 1 and 2 under 35 U.S.C. 112(a) (written description)
Applicant argues that the rejection should be withdrawn in view of the amendments to claim 1 (Remarks, pages 9-10).
This argument was persuasive. The rejection has been withdrawn.
Rejection of claims 1 and 2 under 35 U.S.C. 103 as being unpatentable over Gormley in view of Klenchin
Applicant argues that the rejection should be withdrawn (Remarks, pages 10-12). In particular, Applicant argues that “[T]he articulated reasoning set forth by the Office for making the proposed modifications to Gormley is not supported by a rational underpinning” (Remarks, page 12). More specifically, Applicant argues that “[I]t is not rational for the skilled artisan to introduce modification steps to Gormley’s process when the reference provides three straight forward methods for tuning the density using the system components without modification” (Remarks, page 12). Applicant also argues that the references fail to teach or suggest the new requirement in the last three lines of amended claim 1 for the modified transposome complexes to constitute 20-60% of the transposome complexes (Remarks, page 12).
These arguments have been fully considered, but they were not persuasive for the following reasons.
Argument 1:
Applicant’s first argument (i.e., lack of a proper rationale for modifying Gormley) was not persuasive because the rejection does, in fact, set forth a proper rationale for modifying Gormley to arrive at the claimed flow cell. As discussed in the rejection, in the absence of unexpected results, it is prima facie obvious to select a known material or method based on its suitability for the intended purpose (MPEP 2144.07). In this case, the teachings of Klenchin indicate that removing the 5’ phosphate from the non-transferred strand in a transposome complex reduces tagmentation efficiency, the ordinary artisan would have recognized that this modification would also be suitable for the intended purpose of reducing tagmentation efficiency in Gormley. Then, since no evidence of unexpected results has been presented, a prima facie case of obviousness exists per MPEP 2144.07.
Attention is also directed to MPEP 2143 I, which discusses proper rationales for establishing obviousness. These rationales include (i) “combining prior art elements according to known methods to yield predictable results” and (ii) “simple substitution of one known element for another to obtain predictable results.” Each of these rationales apply to the instant case for the following reasons.
As to (i), the prior art includes all of the claimed elements in the two cited references, with the difference being that all of the required elements are not found in a single reference. As well, the ordinary artisan would have reasonably considered combining the density tuning methods disclosed in Gormley with the modified transposome complexes disclosed in Klenchin to only require routine experimentation given the guidance throughout Gormley and Klenchin. The ordinary artisan also would have considered the density tuning methods of Gormley and the modified transposome complexes of Klenchin to offer the same property (predictably reduced tagmentation efficiency) alone or in combination because there is nothing in the references or the prior art as a whole to suggest that the presence of some transposomes lacking a 5’ phosphate on the non-transferred strand would affect the properties of other transposomes lacking the modification.
As to (ii), the prior art discloses a flow cell in Gormley that differs from the claimed flow cell by lacking the presence of modified transposomes, and the prior art of Klenchin discloses the substituted component (i.e., modified transposomes in which the 5’ phosphate is not present in the non-transferred strand). The ordinary artisan could have substituted some of the unmodified transposomes in Gormley with the modified transposomes of Klenchin and would have expected predictable results since the modified transposome complexes studied by Klenchin contain the same transposase (Tn5) used in the methods of Gormley and there is nothing in the references or the prior art as a whole to suggest that the presence of some transposomes lacking a 5’ phosphate on the non-transferred strand would affect the properties of other transposomes lacking the modification.
Lastly, it is noted that Gormley contains nothing that would constitute a teaching away from combining the disclosed transposome density tuning methods with other methods that will have the same effect of increasing fragment length by reducing transposome efficiency. For example, an ordinary artisan unable to achieve the desired degree of reduced transposome efficiency using only Gormley’s density tuning methods would be motivated to seek other methods, such as Klenchin’s use of transposome complexes that lack a 5’ phosphate on the non-transferred strand, to achieve the desired degree of reduced tagmentation efficiency.
Argument 2:
Applicant’s second argument (i.e., failure of the references to meet the new requirement in the last three lines of amended claim 1) was unpersuasive because the references do, in fact, render obvious the new requirement for the modified transposome complexes to constitute 20-60% of the transposome complexes. As discussed in more detail in the modified rejection, the ordinary artisan would have recognized from the teachings of Gormley that the amount of modified transposomes was a results-effective variable and would, therefore, have been motivated to optimize the amount of modified transposomes using routine experimentation, which is prima facie obvious per MPEP 2144.05 II since no evidence of unexpected results has been presented.
Since Applicant’s arguments were not persuasive, the rejection has been maintained with modifications to address the amendments to claim 1 and the cancellation of claim 2.
Priority
4. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 365(c) or 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the four prior-filed provisional applications and also the prior-filed non-provisional application (i.e., PCT/US2022/082280), fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
In particular, as discussed below, amended claim 1 contains new matter. The prior-filed applications, the disclosures of which are incorporated by reference into the instant application, also fail to provide support for the percentage range recited in the last three lines of amended claim 1. Accordingly, the effective filing date of claim 1 is December 23, 2022.
Drawings
5. The replacement drawing sheet filed on March 30, 2026 is acceptable.
Claim Interpretation
6. The specification of the instant application includes explicit (i.e., limiting) definitions for some terms used in the claims. These definitions include the following:
(i) amplification domain = a portion of an adapter having a universal nucleotide sequence, such as a P5 or P7 sequence, that can serve as a starting point for template amplification and cluster generation (page 11, para. 71);
(ii) depression = a discrete concave feature in a substrate or a layer of a substrate (e.g., a patterned resin) having a surface opening that is at least partially surrounded by interstitial region(s) of the substrate or the layer (page 11, para. 75);
(iii) flow cell = a vessel having a flow channel where a reaction can be carried out, an inlet for delivering reagent(s) to the chamber, and an outlet for removing reagent(s) from the chamber (page 13, para. 79);
(iv) transposome complex = a complex formed between a transposase and a double-stranded nucleic acid including a transposase integration recognition site (pages 14-15, para. 87);
(v) transferred strand = a sequence that includes a transferred portion of a transposon end (page 14, para. 85); and
(vi) non-transferred strand = a sequence that includes the non-transferred portion of a transposon end (page 14, para. 85).
Claim Rejections - 35 USC § 112
7. The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 1 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 has been amended in its concluding “wherein” clause to require that the percentage of first and/or second transposome complexes containing the modification to reduce tagmentation efficiency ranges from 20-60% of the total number of first and second transposome complexes.
As noted previously, Applicant has elected “exclusion of a 5’ phosphate group at a 5’ end of a non-transferred strand of some of the first and/or second transposome complexes” as the species of modification to reduce tagmentation efficiency for examination. This elected species is recited as option (a) in amended claim 1.
Applicant’s response filed on March 30, 2026 points to at least para. 426 of the specification as providing support for the amendments to claim 1 (Remarks, page 12).
The original disclosure, including the portion cited by Applicant, has been reviewed, but support was not found for the percentage range recited in the last three lines of amended claim 1. Para. 426 discloses the claimed percentage range, but only in the context of a different modification that reduces tagmentation efficiency (dideoxycytosine at a 3’ end of a transferred strand). There is nothing in the specification to support the claimed percentage range for other modifications (e.g., the elected modification of exclusion of a 5’ phosphate at the 5’ end of a non-transferred strand). Accordingly, claim 1 is rejected for containing new matter.
Claim Rejections - 35 USC § 103
8. The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
9. 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.
10. Claim 1 is rejected under 35 U.S.C. 103 as being unpatentable over Gormley et al. (US 2014/0194324 A1) in view of Klenchin et al. (Nucleic Acids Research 2008; 36: 5855-5862).1
Claim 1 is drawn to a flow cell. The flow cell comprises a substrate with depressions separated by interstitial regions. First and second primers are immobilized in the depressions as are first and second transposome complexes. Further, some of the first and/or second transposome complexes “include a modification to reduce tagmentation efficiency.” In terms of the modification, Applicant previously elected species (A1) (exclusion of a phosphate group at the 5’ end of a non-transferred strand of some of the first and/or second transposome complexes) for examination.
Regarding claim 1, Gormley discloses a solid support upon which a plurality of transposome complexes are immobilized (see, e.g., para. 6; see also Figs. 2a, 3a, and 5d as well as the accompanying descriptions in paras. 17, 19, 22, 64, and 65). The solid support may be a substrate present in a flow cell (see, e.g., paras. 19, 22, 41, 52, and 65). As well, two different types of transposome complex, each containing a different amplification domain, may be immobilized on the surface of the flow cell (see, e.g., paras. 19 and 65). Still further, Gormley teaches that solid supports may comprise “an array of wells or depressions in a surface” (para. 54). This, in combination with the surrounding teachings in Gormley in paras. 50-53 and 55, clearly suggests “a flow cell comprising a substrate having depressions separated by interstitial regions” as recited in claim 1.
Gormley is not anticipatory for three reasons. First, the reference does not clearly teach immobilizing the transposome complexes in the depressions on the substrate of the flow cell. This is required by claim 1. Second, Gormely does not clearly teach that first and second primers are also immobilized in the depressions together with the transposome complexes. This is also required by claim 1. Third, Gormley does not teach that some of the first and/or second transposome complexes include “a modification to reduce tagmentation efficiency” as recited in claim 1. As a result, Gormley also does not satisfy the new language in option (a) in amended claim 1, which recites the elected species of modification—exclusion of a 5’ phosphate on the non-transferred strand.
Prior to the effective filing date of the claimed invention, though, it would have been prima facie obvious for the ordinary artisan to immobilize the two different transposome complexes disclosed in, e.g., Figure 3 of Gormley in the depressions that may be present on the substrate of the flow cell. As discussed above, Gormley clearly teaches immobilizing the transposome complexes on a substrate of the flow cell and that said substrate may contain depressions. The ordinary artisan would have recognized that immobilizing the transposome complexes in the depressions would allow different transposome complexes or groups of transposome complexes to be separated from another in the flow cell, thereby facilitating highly parallel processing and analysis. The ordinary artisan also would have recognized that the two different types of transposome complexes disclosed in Gormley could be provided in the same depression since such clusters on the flow cell surface were disclosed as suitable (see, e.g., Fig. 3a and paras. 19 and 65). The ordinary artisan would have had a reasonable expectation of success in view of the guidance in Gormley concerning immobilization of transposome complexes (see, e.g., paras. 50-55). The teachings of Gormley also render obvious the requirement in claim 1 for each of the depressions in the flow cell substrate to contain immobilized first and second primers in additional to the immobilized transposome complexes. In particular, Gormley teaches that the length of the fragments generated by tagmentation “can be varied by changing the density of the transposome complexes on the surface” (para. 58). Gormley further teaches solid supports upon which varying amounts of transposome complexes are immobilized (see, e.g., para. 58). Still further, Gormley teaches forming the immobilized transposome complexes by extending first and second primers also immobilized on the substrate of the flow cell (see, e.g., Fig. 5d and paras. 22 and 98). When the above teachings of Gormley are considered together, the ordinary artisan would have recognized that, depending on the amount of transposome complexes formed on the substrate of the flow cell, excess first and second primers that are not part of a transposome complex would also be present (i.e., immobilized) on the flow cell substrate. In other words, the teachings of Gormley do not suggest that every first and second primer immobilized on the flow cell substrate becomes part of a transposome complex, particularly when a lower density of transposome complexes is desired. Therefore, the reference necessarily suggests a flow cell in which the depressions on the substrate contain immobilized first and second primers in addition to first and second transposome complexes.
Finally, it would have been prima facie obvious to modify some of the first and/or second immobilized transposome complexes such that the non-transferred strands do not contain a 5’ phosphate. As noted above, Gormley teaches that the length of the fragments generated by tagmentation “can be varied by changing the density of the transposome complexes on the surface” (para. 58; see also para. 107). Gormley expands on this teaching in paragraph 100, stating, “Fragment size is a function of the ratio of transposomes to the amount and size of DNA and to the duration of the reaction.” Paragraph 100 of Gormley additionally notes that small fragments with lengths shorter than the combined paired-read lengths are undesirable and require removal prior to downstream amplification and sequencing. Taken together, these teachings of Gormley indicate that it can be desirable for the tagmentation reaction to produce longer fragments (i.e., by cleaving less frequently/or efficiently). Thus, Gormley provides motivation to decrease the efficiency of tagmentation (e.g., by decreasing the density of transposome complexes on the surface as discussed in paras. 58 and 107).
Then, since Klenchin taught that tagmentation efficiency markedly decreases when the non-transferred strand in a transposome complex lacks a 5’ phosphate (abstract and the first subsection of the Results section on pp. 5857-5858), the ordinary artisan would have been motivated to incorporate this modification into at least some of the immobilized transposome complexes of Gormley to obtain an additional or alternative means of reducing tagmentation efficiency and obtaining larger fragments for downstream analysis. The ordinary artisan would have had a reasonable expectation of success since the modified transposome complexes studied by Klenchin contain the same transposase (Tn5) used in the methods of Gormley (see, e.g., paras. 12, 44-45, and 64 of Gormley and the first subsection of the Results section on pp. 5857-5858 of Klenchin). Still further, attention is directed to MPEP 2144.07, which notes that, in the absence of unexpected results, it is prima facie obvious to select a known material or method based on its suitability for the intended purpose. In this case, the teachings of Klenchin indicate that excluding a 5’ phosphate from the non-transferred strand in a trasposome complex results in reduced tagmentation efficiency, and no evidence of unexpected results has been presented. This is sufficient to establish a prima facie case of obviousness.
Lastly, as to the new requirement in claim 1 for 20-60% of the total amount of first and second transposome complexes to be modified, it is noted that it is prima facie obvious to optimize results-effective variables in the absence of unexpected results (MPEP 2144.05 II). In this case, the ordinary artisan would have recognized from the teachings of Gormley in at least paras. 58, 100, and 107 that transposase efficiency is a results-effective variable since it influences the length of the nucleic acid fragments to be amplified and sequenced. Therefore, when incorporating the modified transposome complexes suggested by Klenchin into the flow cells of Gormley, the ordinary artisan would have recognized that the amount of modified transposome complexes should be optimized to obtain the desired reduction in transposome efficiency and corresponding increase in fragment length. And, since no evidence of unexpected results has been presented with respect to the claimed percentages, they are prima facie obvious over Gormley in view of Klenchin.
Thus, the flow cell of claim 1 is prima facie obvious.
Conclusion
11. No claims are currently allowable.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Angela Bertagna whose telephone number is (571)272-8291. The examiner can normally be reached 8-5, M-F.
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/ANGELA M. BERTAGNA/Primary Examiner, Art Unit 1681
1 These references were cited in the last Office action.
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