DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This action is in response to papers filed 8/19/2025.
Applicant’s election without traverse of Group I in the reply filed on 3/29/2024 is acknowledged.
Claims 1-2, 6, 8-9, 14-26 are pending. Claims 3-5, 7, 10-13, 27 have been cancelled. Claims 9, 14-26 are withdrawn based upon the election of Group I in the reply to restriction.
The following rejections are modified necessitated by amendment with response to arguments follows.
This action is FINAL.
Claim Rejections - 35 USC § 103
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.
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.
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.
Claim(s) 1-2 is/are rejected under 35 U.S.C. 103 as being unpatentable over Iafrate et al. (US Patent Application Publication 2015/0211061 July 30, 2015) in view of Myllykangas (PMC 2015 cited on IDS).
With regard to claim 1, the term “kit” isn’t given any patentable weight as it appears that the kit merely requires the collection of the structures that are set forth in claim 1. The kit comprises a flow cell with a substrate and a genotyping probe fluid.
With regard to the flow cell, Iafrate et al. teaches a flow cell substrate with multiple primers wherein the primer can contain a target sequence of an endonuclease (para 66). As such Iafrate et al. teaches a flow cell that has the same structures as is claimed.
With regard to the liquid carrier, Iafrate et al. teaches a reaction mixture (liquid) that comprises that includes target specific sequences that are single stranded (8-9). Iafrate et al. teaches that the nucleic acid molecule can be identical to a portion that has an index sequence (para 55). This target has a region of interest and as such suggest a probe sequence that is adjacent to the index sequence that represents nucleobase of interest.
However, Iafrate et al. does not teach a second primer sequence that is at least partially complementary to the second capture primer.
With regard to claim 1, Myllykangas et al. teaches structures wherein a second primer sequence is complementary to a capture primer (figure 1) Iafrate and Myllykangas does not teach the specific structures in the same order. It would be prima facie obvious to one of ordinary skill in the art at the time of the effective filing date to perform a rearrangement of known parts of a structure. The rearrangement of the structures would be routine optimization of known structures for an oligonucleotide that comprises the same structural components.
With regard to claim 2, Myllykangas et al. teaches primer probes that will bind to specific target (preparation of OS Seq primer probes and figure 1).
Myllykangas et al. teaches that the second capture primer has a cleavage site (figure 1 and amplification of microarray synthesized oligonucleotides).
Therefore it would be prima facie obvious to one of ordinary to modify the structure of Iafrate to rearrange known primer and probe components to detect target regions with the flow cell substrate using capture primers and a primer in the liquid reaction (as taught by Myllykangas et al). It would be a reasonable expectation of success of a design of primers, probe and targets that allow for detection of target regains in a sample based upon hybridization and detection of the substrate.
Response to Arguments
The reply traverses the rejection. A summary of the arguments is provided below with response to arguments following.
The reply asserts that the references do not teach the segments in the 3 to 5 order as claimed (p. 10-11). The reply asserts that the purpose of lafrate for enrichment and therefore the enzyme site for cleavage does not provide guidance to arrive at the sequence of the genotyping oligonucleotide (p. 12). The reply asserts that the purpose of Myllykangas is for amplifying a target sequence on a flow cell surface and not for cleaving to expose a particular nucleobase (p. 12-13).
These arguments have been reviewed but are not found persuasive.
As noted above the genotyping oligonucleoside of the combination of Iafrate and Myllykangas does not provide the same structure in the same order from 3’ to 5’ end, but appears to be a rearrangement of the known parts. The reply has not provided that the rearrange is more than mere routine optimization of parts of an oligonucleotide structures. Furthermore although Iafrate is directed to enrichment, the enzyme site of Iafrate is used for the same purpose as a stie where endonuclease can cleave. Further the claims are not drawn to methods of exposing a particular nucleobase, however, as noted above the combination of Myllykangas and Iafrate have the same structural components and would be capable of the same functionality.
Claim(s) 6, 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Iafrate et al. (US Patent Application Publication 2015/0211061 July 30, 2015) and Myllykangas (PMC 2015 cited on IDS) as applied to claims 1-2 and in view of Barany et al. (EP3567122 11/13/2019 previously recited on PTO892)
Iafrate et al. teaches a flow cell substrate with multiple primers wherein the prime can contain a target sequence of an endonuclease (para 66). As such Iafrate et al. teaches a flow cell that has the same structures as is claimed.
With regard to the liquid carrier, Iafrate et al. teaches a reaction mixture (liquid) that comprises that includes target specific sequences that are single stranded (8-9). Iafrate et al. teaches that the nucleic acid molecule can be identical to a portion that has an index sequence (para 55). This target has a region of interest and as such suggest a probe since that is adjacent to the index sequence that is represented to nucleobase of interest. Myllykangas et al. teaches structures wherein a second primer sequence is complementary to a capture primer (figure 1) wherein the probe sequence is attached to the sequence primer sequence.
Iafrate et al. and Myllykangas et al. do not teach that the capture primers are within depression and that the restriction endonuclease sites are Type IIS methyl sensitive restriction endonuclease.
With regard to claims 6, Barany et al. teaches a primer with a cleavage site (p 85 liens 50-55). Barany et al teaches a FokI site (4 based Type IIS) (para 288).
With regard to claim 8, Barany et al. teaches a substrate that comprises depressed regions (para 47) and primers can be attached (para 48).
Therefore it would be prima facie obvious to one of ordinary skill in the art at the time of the effective filing date to modify the structures of Iafrate et al and Myllykangas et al. to include a substrate with depressed regions and using the restriction enzyme site of Barany et al. The ordinary artisan would be motivated to use a substrate with depressed regions as taught by Barany et al. as this is a one of a finite number of substrates in which primers can be attached for detection determination. Further one of the finite number of restriction enzymes is taught by Barany et al. The ordinary artisan would have a reasonable expectation of success of using an enzyme to cleave.
Response to Arguments
The reply traverses the rejection. A summary of the arguments is provided below with response to arguments following.
The reply asserts that Barany cleavage sites allow crosslinking oligonucleotides to fall apart and get captured on a surface, but does not teach arranging the cleavage site to expose a particular nucleobase for genotyping (p. 13).
These arguments have been reviewed but have not been found persuasive.
The reply asserts that the reference does not teach complementary restriction enzyme sites that can be used to generate a double stranded bridge that provides a substrate for restriction enzyme cleavage, however, the structure of the claims do not require such a limitation. The structure requires a second capture primer having a restriction endonuclease site and a second restriction endonuclease site, these structures do not require the claimed complementary restriction enzyme sites that can be used to generate a double stranded bridge that provides a substrate for restriction enzyme cleavage. Barany et al. teaches a substrate that comprises depressed regions (para 47) and primers can be attached (para 48). Barany et al. teaches a primer with a cleavage site (p 85 liens 50-55). Barany et al teaches a FokI site (4 based Type IIS) (para 288). This structure is the same as claimed in claim 6 of an endonuclease sites are sensitive to a type IIS methyl sensitive restriction endonuclease.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 KATHERINE D SALMON whose telephone number is (571)272-3316. The examiner can normally be reached 9-530.
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/KATHERINE D SALMON/Primary Examiner, Art Unit 1682