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 .
2. Please note that the examiner for this application has changed. Please address future correspondence to Robert T. Crow (Art Unit 1683) whose telephone number is (571) 272-1113.
Continued Examination Under 37 CFR 1.114
3. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 30 January 2026 has been entered.
Amendments and Status of the Claims
4. This action is in response to papers filed 30 January 2026 in which claims 124 and 130 were amended, no claims were canceled, and no new claims were added. All of the amendments have been thoroughly reviewed and entered.
Any previous objections and/or rejections not reiterated below are withdrawn in view of the amendments.
5. Claims 124-125, 128-131, 137-139, 148-151, 161, 193-194, and 197-198 are under prosecution.
Terminal Disclaimer
6. The terminal disclaimer filed on 27 August 2025 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of U.S. Patent No. 11,299,780 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Claim Interpretation
7. The claims listed below are subject to the following interpretation.
A. As noted in the previous Office Action, claim 124 (upon which claims 125, 128-131, 137-139, 148-151, 161, 193-194, and 197-198 depend) contains the recitation “the oligonucleotide pool comprises oligonucleotides that comprise a double-stranded portion and an overhang, or the oligonucleotide pool comprises oligonucleotides that comprise a double-stranded portion and an overhang and oligonucleotides that comprise a double- stranded portion and no overhang” (emphasis added). The inclusion of “or” indicates that the oligonucleotide pool may only comprise oligonucleotides that have a double-stranded portion and an overhang and would not contain oligonucleotides that do not have an overhang.
For purposes of prior art consideration, the claims encompass an oligonucleotide pool that is comprised of both oligonucleotides that do and do not have overhangs is not required.
B. The preambles of claims 193 and 194 each recite a “kit.” The specification, however, does not define this term, and so it is being interpreted to encompass any collection of reagents that includes all of the elements of the claims. Any further interpretation of the word is considered an “intended use” and does not impart any further structural limitation of on the claimed subject 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. Claims 124-125, 128, 130-131, 137-138, 131, 161, 193-194, and 197-198 are rejected under 35 U.S.C. 103 as being unpatentable over Watson (U.S. Patent Application Publication No. US 2013/0225418 A1, published 29 August 2013) m combination with Peter et al. (U.S. Patent Application Publication No. US 2009/0181375 A1, published 16 July 2009).
Regarding claim 124, Watson teaches a composition comprising a barcoded oligonucleotide pool (paragraph 0079) wherein the oligonucleotides comprise a double stranded portion and an overhang (e.g., Figure 5), wherein the overhangs are complementary to, and thus capable of, hybridizing to respective target nucleic acids (e.g., Figure 5 and paragraph 0149). Watson further teaches that oligonucleotides comprise a barcode region (i.e., the claimed complementary region identification polynucleotide) adjacent to the complementary region (e.g. Figure 2 and paragraph 0127), and that the barcodes are unique and are of any length (paragraph 0025). Watson further teaches the overhangs (i.e., sticky ends) are any length (paragraph 0149).
Figure 2 of Watson clearly shows overhangs having barcodes adjacent the two ends. Paragraph 0025 of Watson states that the barcode library is comprised of constructs containing sticky ends (i.e., overhangs) a unique N-mer (i.e., the barcode) and functional N-mers, which are sequence specific primers. Paragraph 0010 of Watson states that the N-mers are hybridized to the target nucleic acids. Thus, there is clearly overhangs at both ends (Figure 2) with a barcode that is adjacent to a sequence complementary to an overhang that binds the target.
Watson also teach the oligonucleotides have the added advantage of being useful for sequencing, digital PCR, and array hybridization (paragraph 0149). Thus, Watson teaches the known techniques discussed above.
Watson does not explicitly teach the length of the barcode is specific to the length of the complementary region.
However, Peter et al. teach barcoded oligonucleotides having overhangs, wherein the barcodes are not equal lengths, which allows the duplexes to have similar melting temperatures (paragraph 0067). Because melting temperature is related to the length of the oligonucleotide (paragraph 0026), it would have been obvious to have the total lengths of the oligonucleotides be the same. Thus, a longer target complementary region requires a shorter barcode, and vice versa, which results in the barcode length being specific for the length of the target complementary region. Peter et al. also each the oligonucleotides have the added advantage of allowing detection on one array (paragraph 0067). Thus, Peter et al. teach the known techniques discussed above.
It is also noted that the courts have found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II. Thus, tuning the length of the barcode to the target length to achieve similar melting points also merely represents optimization of the lengths of the two segments to achieve the desired melting temperature.
Applicant is advised that MPEP 716.01(c) makes clear that “[t]he arguments of counsel cannot take the place of evidence in the record” (In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965)). Thus, Applicant should not merely rely upon counsel’s arguments in place of evidence in the record.
It would therefore have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of Watson and Peter et al. to arrive at the instantly claimed composition with a reasonable expectation of success. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in a composition having the added advantages of being useful for sequencing, digital PCR, and array hybridization as explicitly taught by Watson (paragraph 0149) and allowing detection on one array as explicitly taught by Watson (paragraph 0067). In addition, it would have been obvious to the ordinary artisan that the known techniques of the cited prior art could have been combined with predictable results because the known techniques of the cited prior art predictably result in oligonucleotides useful for array and PCR based assays.
Regarding claim 125, the composition of claim 124 is discussed above. Watson teaches a 5’ overhang (e.g., Figure 3). In addition, it is noted that sticky end must be either at the 5’ or 3’ end.
Regarding claim 128, the composition of claim 124 is discussed above. Watson teaches the composition is a droplet libray (Figure 3 and paragraph 0013); thus, the composition is a liquid composition.
Regarding claim 130, the composition of claim 124 is discussed above. Watson teaches the overhangs hybridize to targets (paragraph 0149).
Regarding claim 131, the composition of claim 124 is discussed above. Watson teaches the oligonucleotides comprise an overhang at one end or an overhang at both ends; that the overhang independently comprises a 5’ overhang or a 3’ overhang; and that the overhang comprises the complementarity region (Figure 3, “single sticky end oligo barcodes” vs “double sticky end oligo barcodes”).
Regarding claim 137, the composition of claim 131 is discussed above. Watson teaches the barcode comprises a unique priming sequence in which the primer can either be forward (specific to the 5’ overhang oligos) or reverse (specific to the 3’ overhang oligos; Figures 4 and 5). Additionally, each sticky-end has a specific overhang sequence with an associated barcode sequence; thus, the barcodes identify the overhang as 5’ or 3’.
Regarding claim 138, the composition of claim 131 is discussed above. Watson teaches double-stranded oligos with overhangs on one or both ends, which necessarily means that the oligos consist of a first strand with a polynucleotide sequence complementary to a polynucleotide sequence in a second strand (Figure 3); thus, the oligonucleotides consist essentially of two strands.
Regarding claim 161, the composition of claim 131 is discussed above. Watson teaches that the oligonucleotides can comprise a portion other than the complementarity region and the complementarity region identification polynucleotide, in the form of a universal priming site (paragraph 0130) or priming sites for sequencing (paragraph 0149).
Regarding claim 193, the composition of claim 124 is discussed above. Watson teaches the oligonucleotides are in droplets (paragraph 0018), the droplets are pooled (paragraph 0078), and the droplets are in a storage vessel (paragraph 0112). Page 41 of the instant specification states that kits include any of the compositions described therein. Thus, the vessel is a kit, and the claim has been given the broadest reasonable interpretation consistent with the teachings of the specification regarding a “kit” (In re Hyatt, 211 F.3d1367, 1372, 54 USPQ2d 1664, 1667 (Fed. Cir. 2000) (see MPEP 2111).
It is noted that the courts have found that “the content of the printed matter will not distinguish the claimed product from the prior art (In re Ngai, 367 F.3d 1336, 1339, 70 USPQ2d 1862, 1864 (Fed. Cir. 2004)).” See MPEP 2112.01 III. Therefore, because the courts have stated that the inclusion of instructions with an old product is obvious, the instant claim is obvious.
Regarding claim 194, the kit of claim 193 is discussed above. Watson teaches the droplets are amplified using either a liasge chan reaction or a ligase detection reaction (paragraph 0096). Peter et al. also teach DNA ligase (paragaph 0054). Thus, it would have been obviou to include a DNA ligase.
Regarding claims 197-198, the composition of claim 124 is discussed above. Watson teaches the oligonucleotides of the barcode library include constructs having a functional N-mer and a unique N-mer” and “a functional N-mer is a sticky end.”, paragraph [0140]) and a particular 5’ or 3’ directionality (each sticky-end having a specific overhang sequence with an associated barcode sequence would necessarily mean that the barcode would identify the overhang as 5’ or 3’). Peter et al. teach the barcodes are not equal lengths, which allows the duplexes to have similar melting temperatures (paragraph 0067), thereby resulting in the barcode length being specific for the length of the target complementary region as discussed above.
10. Claims 128-129 and 193-194 are rejected under 35 U.S.C. 103 as being unpatentable over Watson (U.S. Patent Application Publication No. US 2013/0225418 A1, published 29 August 2013) in combination with Peter et al. (U.S. Patent Application Publication No. US 2009/0181375 A1, published 16 July 2009) as applied to claim 124 above, and further in combination with Levy et al. (U.S. Patent Application Publication No. US 2010/0311602 A1, published 9 December 2010).
It is noted that while claims 128 and 193-194 have been rejected as described above, the claims are also obvious using the interpretation outlined below.
Regarding claims 128-129 and 193-194, the composition of claim 124 is discussed above in Section 9.
Neither Watson nor Peter et al. teach a lyophilized composition.
However, Levy et al. teach providing reagents necessary for sequencing, including adaptor mixes, enzymes, and primers, in lyophilized form (i.e., claim 129) or liquids (i.e., claim 128), as well as DNA ligase (paragraph 0053) and kits with instructions (i.e., claims 193-194), which have the added advantage of providing the reagents in a stable form (paragraph 0191). Thus Levy et al. teach the known techniques discussed above.
It is reiterated that the courts have found that the content of the printed matter will not distinguish the claimed product from the prior art. Therefore, because the courts have stated that the inclusion of instructions with an old product is obvious, claims 193-194 are obvious.
It would therefore have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of Levy et al. with Watson and Peter et al. to arrive at the instantly claimed compositions with a reasonable expectation of success. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in compositions having the added advantage of providing reagents in stabilized form as explicitly taught by Levy et al. (paragraph 0191). In addition, it would have been obvious to the ordinary artisan that the known techniques of Levy et al. could have been combined with the cited prior art with predictable results because the known techniques of Levy et al. predictably result in stabilized reagents.
11. Claims 139, 148-151 and 193-194 are rejected under 35 U.S.C. 103 as being unpatentable over Watson (U.S. Patent Application Publication No. US 2013/0225418 A1, published 29 August 2013) in combination with Peter et al.. (U.S. Patent Application Publication No. US 2009/0181375 A1, published 16 July 2009) as applied to claims 124 and 131 above, and further in combination with Eshoo et al.. (U.S. Patent Application Publication No. US 2015/0004604 A1, published 1 January 2015).
It is noted that while claims 193-194 have been rejected as described above, the claims are also obvious using the interpretation outlined below.
Regarding claims 139, 148-151, and 193-194, the composition of claims 124 and 131 are discussed above in Section 9.
Whuile Watson teaches hairpins (i.e., stem loops; paragraph 0059), neither Wantson nor Peter et al. teach the oligonucleotides form hairpins (i.e., claim 139).
However, Eshoo et al. teach adapters that are single-stranded oligonucleotides which form hairpin structures with overhangs (i.e., claim 139; Figure 2); thus, the oligonucleotides consist essentially of one strands. Eshoo et al. also teach polynucleotide sequence overhangs that are 1, 2, or 3 nucleotides long (i.e., claims 148-150; paragraph 0029), and that the oligonucleotide adapters can contain overhangs with random sequences (i.e., claim 151; paragraph 0007).
Eshoo et al. further teach kits and ligase (i.e., claims 193-194; paragraph 0007), and that the methods and kits have the added advantage of allowing efficient ligation of products with overhangs of varied or unknown sequences (paragraph 0026). Thus, Eshoo et al. teach the known techniques discussed above.
It is reiterated that the courts have found that the content of the printed matter will not distinguish the claimed product from the prior art. Therefore, because the courts have stated that the inclusion of instructions with an old product is obvious, claims 193-194 are obvious.
It would therefore have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of Eshoo et al. with Watson and Peter et al. to arrive at the instantly claimed compositions with a reasonable expectation of success. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in compositions having the added advantage of allowing efficient ligation of products with overhangs of varied or unknown sequences as explicitly taught by Eshoo et al. (paragraph 00267). In addition, it would have been obvious to the ordinary artisan that the known techniques of Eshoo et al. could have been combined with the cited prior art with predictable results because the known techniques of Eshoo et al. predictably result in oligonucleotides useful for array and PCR based assays.
Response to Arguments
12. Applicant's arguments filed 30 January 2026 m(hereafter the “Remarks”) have been fully considered but they are not persuasive for the reasons discussed below.
A. Page 6 of the Remarks refer to the amendments the previous rejections under 35 U.S.C. 112(b) and (d), which have been withdrawn in view of the amendments.
B. While the claims are no longer anticipated in view of Watson, the arguments regarding Watson are considered below.
C. Applicant argues on pages 7-8 of the Remarks that Watson does not teach an overhang having a target complementary regions and a barcode regions adjacent thereto.
However, Figure 2 of Watson clearly shows overhangs having barcodes adjacent the two ends. Paragraph 0025 of Watson states that the barcode library is comprised of constructs containing sticky ends (i.e., overhangs) a unique N-mer (i.e., the barcode) and functional N-mers, which are sequence specific primers. Paragraph 0010 of Watson states that the N-mers are hybridized to the target nucleic acids. Thus, there is clearly overhangs at both ends (Figure 2) with a barcode that is adjacent to a sequence complementary to an overhang the target.
D. In response to Applicant's argument on page 8 of the Remarks that the references fail to show certain features of the invention, it is noted that the features upon which Applicant relies (i.e., a barcode in the overhang) are not recited in the rejected claim(s). 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).
Claim 124 specifically states that the oligonucleotides that comprise an overhang have a complementarity region capable of hybridizing to an overhang (which would be a sticky end) and “a region adjacent to…” The adjacent region is NOT required to be in the overhang.
E. Pages 8-9 of the Remarks reiterate the arguments of Watson, which are addressed above.
E. In response to Applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, the motivations to combine the references are clearly articulated above.
In addition, it is also noted that the Supreme Court ruling for KSR Int’l Co. v. Teleflex, Inc. (No 04-1350 (US 30 April 2007) forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness. See Ex parte Smith (USPQ2d, slip op. at 20 (Bd. Pat. App. & Interf. June 25, 2007).
F. Applicant argues that the proposed modification renders Watson unsatisfactory of for it’s intended purpose.
Applicant’s arguments appears to state that having more than one barcode region ligated in succession prohibits the primers from being produced.
However, any additional barcode regions in the oligonucleotide pool are encompassed by the open claim language “comprising” found in the instant claims.
In addition it is reiterated Figure 2 of Watson clearly shows overhangs having barcodes adjacent the two ends. Paragraph 0025 of Watson states that the barcode library is comprised of constructs containing sticky ends (i.e., overhangs) a unique N-mer (i.e., the barcode) and functional N-mers, which are sequence specific primers. Paragraph 0010 of Watson states that the N-mers are hybridized to the target nucleic acids. Thus, there is clearly overhangs at both ends (Figure 2) with a barcode that is adjacent to a sequence complementary to an overhang the target. The overhangs can still be ligated to targets and/or amplification can be performed.
Conclusion
13. No claim is allowed.
14. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Robert T. Crow whose telephone number is (571)272-1113. The examiner can normally be reached M-F 8:00-4:30.
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Robert T. Crow
Primary Examiner
Art Unit 1683
/Robert T. Crow/Primary Examiner, Art Unit 1683
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