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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 6/18/2025 has been entered.
Applicants Amendment
Applicant’s amendment filed 6/18/2025 has been received and entered. Claims 1 and 3 have been amended and claims 2 (deleting reference to Hamming distance for numerical tag) and 4 (deleting limitation that decoding is a mathematical operation) have been cancelled, and claim 15 has been added.
Claim 1, 3, 5-15 are pending.
Election/Restriction
Applicant’s election without traverse of Group I, claims 1-6, in the reply filed on 6/2/2022 was acknowledged.
Claims 1, 3, 5-15 are pending.
Newly added claim 15 depends on claim 1 and is consistent with the previously examined invention. Claims 7-14 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1, 3, 5, 6, 15 drawn to a method of tagging a nucleic acid to create an ID number are currently under examination.
Priority
This application filed 4/20/2020 is a 371 National stage filing of PCT/EP2018/078810 filed 10/19/2018 and claims benefit to foreign application EP17197597.2 filed 10/20/2017 in the EP.
No comments on the summary of priority are provided in the instant response.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 2 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn.
Claim 2 has been cancelled.
Claims 1 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn.
The claim has been amended to indicate the ‘nucleic acid tag corresponds to a number ranging from 0 to 3’ is associated clearly with the bases A, G, T or C has addressed the basis of the rejection.
Claims 3 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn.
The claim has been amended to define more clearly the values associated with pk.
New rejections in light of amendments
Claim 15 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Specifically, newly added claim 15 sets forth that the ‘tag does not comprise a watermark sequence’ and in review of the specification it appears that there is adequate figurative support for a designed tag not to comprise a ‘watermark sequence’. For example, on page 10, the specification teaches:
“The main function of the watermark sequence in NS barcodes is to provide a well-known rail of synchronism when decoding barcodes in the presence of indels. As would be expected, removing the watermark sequence in NS barcodes negatively affects decoding performance (see Fig. 4), with increased values of the critical probability of undetected decoding errors for the same level of sequencing noise. To compensate the loss of decoding performance in NS barcodes when removing the watermark sequence, complementary information is needed at the decoder.
In the barcodes disclosed herein, soft decision decoders in the Euclidean space are used to compensate the absence of a watermark sequence that enables the scalable synthesis of barcodes.”
However, at issue is the relative nature of interpreting any sequence used as a tag as comprising or not comprising a ‘watermark’ and establishing a clear metes and bounds of the claims. More specifically, the specification teaches that the codebook can be effectively any sequence and is simply a linear predefined code. For example on page 14 the specification teaches:
“The barcodes built from predefined linear code C and codebook E(C- pairs) disclosed herein are decoded using a two-step decoding approach designed to handle symbol-wise confidence (soft) inputs, and to provide symbol-wise (soft) confidence outputs.”
Which appears to also be descriptive a watermark barcode, or any sequence and simply saying it is watermark, a tag with or without a watermark or something else. In review of the cited references and in view of the guidance of the specification, it appears that a given name to a sequence fails to define the metes and bounds of any given sequence and might at best define how a tag is interpreted. Given the guidance of the specification it appears that the same sequence can be considered a watermark or alternatively one from a codebook or alternatively part of a tag is a watermark and one part is from the codebook all for the same linear tag sequence, and fails to set forth a clear metes and bounds of tag (broadly provided for in claim 1), specifically a tag which does not include a ‘watermark’ as set forth in newly added claim 15.
More specifically providing requirements of the tag where one can distinguish any sequence as a watermark or not would address the basis of the rejection.
Claims 1, 3, 5, 6, 15 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Specifically, claim 1 has been amended to require the use of a ‘pre-defined codebook’ and in review of the specification there is no clear codebook provided as a pre-defined limitation, and vague and unclear as to what the codebook comprises or how it is defined in any way that meaningfully limits the claims in it’s use. Knowing how the codebook is defined, what would be comprised or excluded is critical in defining the metes and bounds of the nucleic acid tags required, also how ‘pre-defined’ somehow limits the nature of the codebook, since any describe sequence appears to provide a basis of defining something.
More clearly providing for what the codebook provides and how it is interpreted to set forth a clear metes and bounds for the nucleic acid sequences which are comprised or excluded from the claim and use as a tag would address the basis of the rejection.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 3, 5, 6 rejected under 35 U.S.C. 102a as being anticipated by Levy et al. (2015) is withdrawn.
Upon reconsideration of the amendments to the claims, it does not appear that Levy specifically recite for using numerical values 0-3 for each of A, T, G or C or a codebook as amended.
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.
Claims 1, 3, 5, 6 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Levy et al. (2015).
Claim 1 has been amended to set forth the that each of the bases A, G, T or C represents 0-3 and are obtained from a ‘pre-defined codebook’ but still appears to provide for any combination that could be designed for a given length. Given the breadth of the claim and guidance of the specification, the tags are different and provide a ‘code’ which can be associated with an ID number. Claim 3 has been amended but still encompasses a tag is 8.
The three active steps of claim 1 require that a nucleic acid sequence is attached to another to provide the attached nucleic acid represents the ID number and then amplification and sequencing the nucleic acid to obtain a read for analysis. Claim 15 has been added to indicate that the tag is not a watermark, but in view of the 112 issues raised above, it is unclear how any tag sequence would be excluded as long as each of the bases can interpreted to represent an ID number for a given tag. The addition of using a codebook, where apparently the sequences and represented ID number is provided is also acknowledged. In review of the specification, the limitations of the tag appear to be descriptive of what the tag sequence could represent, but do not appear to change, affect or limit the ATG or C of a given sequence tag in any specific way. In review of the dependent claims and the specification, it appears that the nucleic acid tag attached to another nucleic acid molecule (claim 5) can also be modified by a detectable label but does not appear to affect or limit the nucleic acid sequence provided in the wherein clause in a way to differentiate the tag from any random sequence or any designed barcode sequence or UMI attached to a nucleic acid of interest. In view of the claim amendments, the scope of the claims do appear to have distinguished any specific design requirements, and thus broadly provides for any sequence or barcode sequence as a tag. Levy does not indicate a ‘codebook’ but the artisan would readily appreciate and know that a tag would have to be informative for use, and that guidance for the association of a given sequence with a given ID would be required and is considered obvious.
As In review of the teachings of Levy et al., there is clearly steps to attach and use barcodes to track alterations in yeast sequences. More specifically, Levy et al. generated yeast lineages by inserting a 20-nucleotide barcode sequences at a single location in the genome noting Figure 1B and supplemental data in SM 1.3. The tagged yeast cultures are allowed to replicate and the barcode is amplified and after selection the genomes are subject to whole genome sequencing for analysis. It is acknowledged that Levy et al. do not specifically state that the barcodes are decoded, but these appear to be descriptive of the nucleic acid barcodes and do not appear to distinguish with any specificity the use of tagging with any barcode and thus is anticipated by Levy et al. Further, Levy et al teach that the 20mer tags were random, however it is clear that each provide informative information and are used to attribute and ID to each of the associated yeast sequences and thus the sample being analyzed.
Response to Applicants 102 Arguments
Applicant provides a summary of Levy et al and argue the claims as amended are distinguished from Levy who use barcode tagging without indicating a finite size or they are composed of tags and not random like that provided by Levy et al.
In response, while there are 112 issues with the amended claims, it is generally agreed that the specific terms of the claims are not provided by Levy et al and the 102 rejection was withdrawn. However, in view of the evidence of record, the teaching of the specification and Levy et al and the art as a whole for the knowledge of the skilled artisan for expectation of success and interpretation of what type of tag is used and how it can be associated with an ID number, the amendments have been evaluated and appear to indicate how one can interpret any given tag sequence and not specifically define any specific design requirements of the tag in a physical way. Claim 15 has been included, because while watermark is not taught by Levy et al., it is not clear what this limitation includes or excludes and does not appear to exclude the tags of Levy et al because the tags are not indicated to be watermarks and thus a plain reading of Levy et al supports that claim 15 is also anticipated by the tags provided in Levy. The claims as amended do not appear to provide any specific requirement, in particular since description of a Hamming relationship suggests that it is simple a measure of difference between regions, and thus would encompass any sequence tag which is 8 or more.
Conclusion
No claim is allowed.
In prosecution additional art of record as evidenced by Bystrykh et al., Buschmann et al. and Church et al. demonstrates that the design and method of attaching barcodes to a sequence for further analysis was known. Each of Bystrykh et al., Buschmann et al. and Church et al. provide for the design and use of barcodes. Each Bystrykh et al., Buschmann et al. and Church et al. provide for 0, 1 and 2 for instruction for what a given sequence could represent and the means to use and decode a sequence. Each Bystrykh et al., Buschmann et al. and Church et al. provide for a variety of methodologies and considerations in the design sequences that provide a means to detect and correct for errors would have been an element of the design and use of a tag sequence.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Joseph T Woitach whose telephone number is (571)272-0739. The examiner can normally be reached Mon-Fri; 8:00-4:00.
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/Joseph Woitach/Primary Examiner, Art Unit 1687