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 .
Election/Restrictions
Applicant’s election without traverse of Group D correspond to claim 73 section (IV) in the reply filed on 08/26/2026 is acknowledged. As a result, claims 74-84 are withdrawn from consideration. Claims 71-72 and 85-90 are generic for or contain the elected subject matter and are under examination. Claim 71 is the only independent claim.
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.
Claim 85 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.
Claim 85 recites the limitation "the second linker" and “the second oligonucleotide” in (i) and (iii), respectively. There is insufficient antecedent basis for this limitation in the claim. Claim 73(IV) recites only a first linker and claim 71 recites a “second polynucleotide”.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 71-73, 86-87, and 89-90 are rejected under 35 U.S.C. 102(a)(1)/102(a)(2) as being anticipated by Bent et al. (US 2020/0063191 A1, published Feb. 27, 2020).
In regards to claim 71, Bent teaches methods of generating barcoded beads by split-pool ligation, and teaches every step of claim 71 as shown in the simplified double-ligation scheme of Figure 9A and its description (see Bent [0159]).
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Regarding step (a), Bent teaches obtaining a population of beads in which a first subpopulation in a first partition (901) is ligated with a first molecule A1 and a second population in a second partition (902) is ligated with a first molecule A2, after which the subpopulations are pooled into a single container (904) (see Bent [0159], [0164] describing ligation of 96 different first molecule in separate wells followed by pooling). The first molecule are polynucleotides that comprises a barcode sequences (see Bent [0136]-[0137]), and A1 and A2 are different molecules carrying different sequences (see Bent [0007], [0012], [0159]).
Bent further teaches splitting the pooled mixture into a plurality of further partitions (906, 907) each of which receives beads carrying each of the different first molecules (see Bent [0159]), generating the claimed pool of second subpopulation of beads reading on step (b).
Bent further teaches ligating a second molecule (B1 in partition 906; B2 in partition 907) to the first molecule on the beads in each partition yielding beads carrying A1B1, A2B1, A1B2, A2B2 (see Bent [0159]). The second molecule comprises a second barcode sequence (see Bent [0138]), and B1 and B2 differ from one another (see Bent [0159]). Ligation of the second molecule to the first molecule extends the first polynucleotide with a second polynucleotide comprising a second index (see Bent [0016], [0034], [0138]). Bent teaches pooling the beads from partitions 906 and 907 into a single container (909), which yields the claimed population of secondary indexed beads (see Bent [0159]). Therefore, Bent teaches all of the limitations of claim 71.
In regards to claim 72, in Figure 10, Bent teaches splitting the pooled secondary population into a plurality of further partitions (1012-1015 in Fig. 10), ligating a different third molecule (C1, C2, C3) in each partition and pooling the resulting beads (see Bent [0162]-[0164]). Bent further teaches that the third molecule comprises a third barcode sequence and that these sequences are different between molecules (see Bent [0139], [0162]-[0164]).
In regards to claim 73 (IV), Bent teaches extending the first polynucleotide by ligation (see Bent [0016], [0033]-[0034], [0137]-[0138]), wherein the first molecule comprises single-stranded overhang sequences, which is the region to which the second molecule is joined (see Bent [0136]-[0138])
In regards to claim 86, Bent teaches “attaching the first polynucleotide to a plurality of first subpopulations of beads to obtain the first subpopulations of indexed beads, wherein the first polynucleotide comprises a different first index for each first subpopulation of beads; and(ii) combining the first subpopulations of indexed beads to obtain the population of primary indexed beads.” (see Bent Figs. 9 and 10, [0159]-[0164]).
In regards to claim 87 and 90, Bent teaches that the ligated beads from the first plate are pooled and mixed and then redistributed among the wells of a second plate as well as taking the secondary indexed beads and randomly distributing them among a further plate (see Bent [0164]).
In regards to claim 89, Bent teaches additional nucleic acids (i.e., barcodes) may be selectively ligated in a similar fashion, ligating 3rd, 4th etc.. barcodes in further subpopulations of beads (see Bent [0149], [0164]).
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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) 71-73, 85-87, and 89-90 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bent et al. (US 2020/0063191 A1, published Feb. 27, 2020) as applied to claims 71-73, 86-87, and 89-90, included here for reasons supra.
In regards to claim 85, Bent teaches that the first nucleic acid molecule, referred to as a “splint oligonucleotide” has a double stranded region and a single stranded region complementary to the starter sequence on the bead, and a single-stranded overhang (see Bent Fig. 13, [0136]-[0137]). The second molecule carries a complementary overhand that hybridizes to the first molecule’s overhang, after which, the two are ligated (see Bent [0138]). The region hybridizing to the bead-bound starter sequence reads on the region “capable of hybridizing to the first linker”, and its overhang reads on the region capable of hybridizing to the second linker. The second molecule hybridizes to that overhang and is then ligated (see Bent [0137]-[0138]).
Claim(s) 71-73, and 85-90 are rejected under 35 U.S.C. 103 as being unpatentable over Bent et al. (US 2020/0063191 A1, published Feb. 27, 2020) as applied to claims 71-73, 85-87, and 89-90, included here for reasons supra in further view of Macosko et al (US 2021/0123040 Al, published Apr. 29, 2021).
In regards to claim 88, Bent teaches the limitations of claim 71 as set forth above. Bent teaches preparing a plurality of combinatorially indexed beads by sequentially ligating different barcode containing polynucleotides to subpopulations of beads using split-and-pool process. Bent does not expressly teach distributing the plurality of combinatorially indexed beads on an array, and sequencing the combinatorially indexed beads on the array.
Macosko teaches distributing barcoded beads on a solid support to form an array of spatially distinguishable beads and determining the barcode sequences of the beads by sequencing the bead-associated barcodes while the beads are positioned on the array. Thus, Macosko teaches the use of and array as a spatial arrangement of barcoded beads in which the respective beads can be distinguished according to their locations and their associated barcodes.
It would have been prima facie obvious to one of ordinary skill in the art at the time of filing to distribute the combinatorially indexed beads of Bent on an array and sequence the combinatorial indexes of the beads as taught by Macosko. One of ordinary skill in the art would have been motivated to do so because positioning the barcoded beads at spatially distinguishable locations on a substrate and sequencing their associated barcodes provides a known means of determining the identify of the bead located at each respective position of the substrate. Applying this known bead array sequencing arrangement to the combinatorially indexed beads of Bent would therefore permit the combinatorial index of bead to identify its respective position on the array with a reasonable expectation of success.
Prior Art
The following prior art also teaches split pool synthesis of barcodes/tags on beads: US 9567646; US 11692214.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Matthew H Raymonda whose telephone number is (703)756-5807. The examiner can normally be reached Monday - Friday 10:00 am - 4:00 pm.
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/MATTHEW HAROLD RAYMONDA/Examiner, Art Unit 1684
/AARON A PRIEST/Primary Examiner, Art Unit 1681
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