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 .
Election/Restrictions
2. Applicant’s election without traverse of the species as recited in claims 35 and 38 in the reply filed on 12/1/2025 is acknowledged.
3. Claims 25-44 are pending in the application. Claims 34 and 39 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 25-33, 35-38 and 40-44 are currently under examination.
Claim Rejections - 35 USC § 112
4. 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.
5. Claims 32-33 are rejected 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 32, dependent from claim 31 which further depends from claim 25, recites the limitation “the first universal sequence” in line 4 and the limitation “the second universal sequence” in lines 5-6. There is insufficient antecedent basis for these limitations in the claim. Claim 33 depends from claim 32 and is thus rejected for the same reason.
Since claim 28 recites “a first universal sequence” (see line 2) and claim 30 recites “a second universal sequence” (see line 2), applicant may amend claim 30 to depend from claim 28 (instead of claim 25) and amend claim 31 to depend from claim 30 (instead of claim 25) to overcome this rejection.
Double Patenting
6. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
7. Claims 25-33, 35-38 and 40-44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 11,649,497. Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-23 of U.S. Patent No. 11,649,497 teach or render obvious all the features as recited in instant claims 25-33, 35-38 and 40-44. Specifically, claims 1-2 of U.S. Patent No. 11,649,497 disclose a method that has all the steps and elements required by the method of instant claim 25 and is more specific. In addition, the other features as recited in instant claims 26-33, 35-38 and 40-44 are also taught or rendered obvious by claims 1-23 of U.S. Patent No. 11,649,497.
Claim Rejections - 35 USC § 102
8. 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 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.
9. 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.
10. Claims 25-26, 28-33, 37-38 and 42-44 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Delley et al. (Sci. Rep. 2018, 8:2919).
Regarding claim 25
Delley et al. teach, throughout the whole document, a method for sample identification, comprising: contacting each of a plurality of samples with a sample indexing composition of a plurality of sample indexing compositions, respectively, wherein each of the plurality of samples comprises one or more cells each comprising one or more cellular component targets, wherein the sample indexing composition comprises a cellular component-binding reagent (e.g., polyadenylated aptamer) associated with a sample indexing oligonucleotide (e.g., sample indexing oligonucleotide comprising the nucleotide sequence of the aptamer as an “intrinsic tag” (see page 2, paragraph 2: “…aptamers are nucleic acids in which the nucleobase sequence provides an intrinsic tag that can be read out via DNA sequencing, obviating the need for additional tag conjugation.”) and the poly-A sequence at 3’-end of the aptamer), wherein the cellular component-binding reagent is capable of specifically binding to at least one of the one or more cellular component targets, wherein the sample indexing oligonucleotide comprises a sample indexing sequence (e.g., the “intrinsic tag” provided by the nucleotide sequence of each aptamer), and wherein sample indexing sequences of at least two sample indexing compositions of the plurality of sample indexing compositions comprise different sequences (see Figure 1; page 2, paragraphs 2-3); contacting the sample indexing oligonucleotides of the plurality of sample indexing compositions with a plurality of oligonucleotide barcodes (e.g., poly-thymine barcode sequences on each bead), wherein each oligonucleotide barcode comprises a first molecular label (e.g., barcode sequence) and a target-binding region (e.g., poly-thymine sequence) capable of hybridizing to the sample indexing oligonucleotide (e.g., the poly-A sequence of the sample indexing oligonucleotide) (see Figure 1; page 2, paragraphs 2-3); extending sample indexing oligonucleotides hybridized to the plurality of oligonucleotide barcodes to generate a plurality of extended sample indexing oligonucleotides each comprising a complement of the first molecular label (see Figure 1; page 2, paragraphs 2-3; page 5, 2nd paragraph from the bottom); denaturing the plurality of extended sample indexing oligonucleotides hybridized to the plurality of oligonucleotide barcodes (see Figure 1; page 2, paragraphs 2-3; page 3, paragraph 2; page 5, 2nd paragraph from the bottom); obtaining sequencing data of the plurality of extended sample indexing oligonucleotides, or products thereof (see Figures 1 and 3; page 2, paragraphs 2-3; page 3, last paragraph – page 4, paragraph 1; paragraph bridging pages 5-6); and identifying the sample origin of at least one cell of the plurality of cells based on the sample indexing sequence of at least one extended sample indexing oligonucleotide, or product thereof, of the plurality of extended sample indexing oligonucleotides, or products thereof, in the sequencing data (see Figures 1 and 3; page 2, paragraphs 2-3; page 3, last paragraph – page 4, paragraph 1; paragraph bridging pages 5-6).
Regarding claim 26
The method according to Delley et al., further comprising separating the plurality of extended sample indexing oligonucleotides from the plurality of oligonucleotide barcodes to generate a plurality of separated extended sample indexing oligonucleotides (see Figure 1; page 2, paragraphs 2-3; page 3, paragraph 2; page 5, 2nd paragraph from the bottom).
Regarding claim 28
The method according to Delley et al., wherein each oligonucleotide barcode comprises a first universal sequence (e.g., part of the poly-thymine sequence can serve as a universal sequence), and wherein the plurality of extended sample indexing oligonucleotides comprise a complement of the first universal sequence (see Figure 1; page 2, paragraphs 2-3).
Regarding claim 29
The method according to Delley et al., wherein sample indexing sequences of at least 10, 100, or 1000 sample indexing compositions of the plurality of sample indexing compositions comprise different sequences (see page 2, paragraphs 2-3; page 4, paragraph 3).
Regarding claim 30
The method according to Delley et al., wherein the sample indexing oligonucleotide comprises a second universal sequence (e.g., known flanking sequence. See page 3, paragraph 2: “…aptamers are constructed with known flanking sequences, which we use for amplification and handle attachment.”).
Regarding claim 31
The method according to Delley et al., wherein identifying the sample origin of the at least one cell comprises identifying the presence or absence of the sample indexing sequence of at least one extended sample indexing oligonucleotide, or product thereof, in the sequencing data (see Figures 1 and 3; page 2, paragraphs 2-3; page 3, last paragraph – page 4, paragraph 1; paragraph bridging pages 5-6).
Regarding claim 32
The method according to Delley et al., wherein identifying the presence or absence of the sample indexing sequence comprises: amplifying the at least one extended sample indexing oligonucleotides, or products thereof, using a primer capable of hybridizing to the first universal sequence, or a complement thereof, and a primer capable of hybridizing to the second universal sequence, or a complement thereof, to generate a plurality of amplified extended sample indexing oligonucleotides; obtaining sequencing data of the plurality of amplified extended sample indexing oligonucleotides, or products thereof; and identifying the sample origin of the cell based on the sample indexing sequence of an amplified extended sample indexing oligonucleotide, or product thereof, of the plurality of amplified extended sample indexing oligonucleotides, or products thereof, that correspond to the at least one extended sample indexing oligonucleotide, or product thereof, in the sequencing data (see page 3, paragraphs 2-3; page 5, 2nd paragraph from the bottom).
Regarding claim 33
The method according to Delley et al., wherein amplifying the at least one extended sample indexing oligonucleotides, or products thereof, comprises attaching sequencing adaptors (e.g., sequencing handles) to the plurality of extended sample indexing oligonucleotides, or products thereof (see page 3, paragraph 2).
Regarding claims 37-38
The method according to Delley et al., comprising removing unbound sample indexing compositions of the plurality of sample indexing compositions, wherein removing the unbound sample indexing compositions comprises washing the one or more cells from each of the plurality of samples with a washing buffer (see Figure 1; page 2, last paragraph).
Regarding claims 42-43
The method according to Delley et al., wherein the target-binding region comprises a poly(dT) sequence (e.g., poly-thymine sequence), and wherein the sample indexing oligonucleotide comprises a poly(dA) region (e.g., poly-A sequence at the 3’-end) (see Figure 1; page 2, paragraphs 2-3); wherein the sample indexing oligonucleotide comprises an alignment sequence adjacent to the poly(dA) region (e.g., the sequence segment adjacent to the poly-A sequence of the aptamer may serve as an alignment sequence).
Regarding claim 44
The method according to Delley et al., wherein a sample of the plurality of samples comprises a plurality of cells, a plurality of single cells, a tissue, a tumor sample, or any combination thereof (see Abstract; Figure 1; page 2, paragraphs 2-3).
11. Claims 25-33, 35-38 and 40-44 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Stoeckius et al. (WO 2018/144813 A1).
Regarding claim 25
Stoeckius et al. teach, throughout the whole document, a method for sample identification, comprising: contacting each of a plurality of samples with a sample indexing composition (e.g., a composition comprising an antibody-oligonucleotide construct) of a plurality of sample indexing compositions, respectively, wherein each of the plurality of samples comprises one or more cells each comprising one or more cellular component targets, wherein the sample indexing composition comprises a cellular component-binding reagent (e.g., antibody) associated with a sample indexing oligonucleotide, wherein the cellular component-binding reagent is capable of specifically binding to at least one of the one or more cellular component targets, wherein the sample indexing oligonucleotide comprises a sample indexing sequence (e.g., antibody barcode which also serves as an indexing sequence for an corresponding sample to which the antibody specifically binds) and a poly(A) sequence, and wherein sample indexing sequences of at least two sample indexing compositions of the plurality of sample indexing compositions comprise different sequences (see Figures 1A-1C; page 5, line 20 – page 6, line 7; paragraph bridging pages 47-48; page 49, line 11 – page 50, line 29; Example 3); contacting the sample indexing oligonucleotides of the plurality of sample indexing compositions with a plurality of oligonucleotide barcodes (e.g., barcoded capture oligonucleotides conjugated to beads), wherein each oligonucleotide barcode comprises a first molecular label (e.g., cell barcode and/or UMI) and a target-binding region (e.g., poly(T) sequence) capable of hybridizing to the sample indexing oligonucleotide (e.g., poly(A) sequence of the sample indexing oligonucleotide) (see Figures 1A-1C; page 5, line 20 – page 6, line 7; paragraph bridging pages 47-48; page 49, line 11 – page 50, line 29; Example 3); extending sample indexing oligonucleotides hybridized to the plurality of oligonucleotide barcodes to generate a plurality of extended sample indexing oligonucleotides each comprising a complement of the first molecular label (see Figures 1A-1C; page 5, line 20 – page 6, line 7; paragraph bridging pages 47-48; page 49, line 11 – page 50, line 29; Example 3); denaturing the plurality of extended sample indexing oligonucleotides hybridized to the plurality of oligonucleotide barcodes (see page 5, line 20 – page 6, line 7; paragraph bridging pages 47-48; page 49, line 11 – page 50, line 29; paragraph bridging pages 105-106; Example 3); obtaining sequencing data of the plurality of extended sample indexing oligonucleotides, or products thereof (see page 43, lines 1-5; page 44, lines 12-19; paragraph bridging pages 46-47; page 49, lines 7-10; page 50, lines 22-27; Example 3); and identifying the sample origin of at least one cell of the plurality of cells based on the sample indexing sequence of at least one extended sample indexing oligonucleotide, or product thereof, of the plurality of extended sample indexing oligonucleotides, or products thereof, in the sequencing data (see page 43, lines 1-5; page 44, lines 12-19; paragraph bridging pages 46-47; page 49, lines 7-10; page 50, lines 22-27; Example 3).
Regarding claim 26
The method according to Stoeckius et al., further comprising separating the plurality of extended sample indexing oligonucleotides from the plurality of oligonucleotide barcodes to generate a plurality of separated extended sample indexing oligonucleotides (see page 5, line 20 – page 6, line 7; paragraph bridging pages 47-48; page 49, line 11 – page 50, line 29; paragraph bridging pages 105-106; Example 3).
Regarding claim 27
The method according to Stoeckius et al., wherein separating the plurality of extended sample indexing oligonucleotides from the plurality of oligonucleotide barcodes comprises magnetic removal, centrifugation, filtration, chromatography, precipitation, or any combination thereof (see paragraph bridging pages 105-106).
Regarding claim 28
The method according to Stoeckius et al., wherein each oligonucleotide barcode comprises a first universal sequence (e.g., PCR handle), and wherein the plurality of extended sample indexing oligonucleotides comprise a complement of the first universal sequence (see Figures 1A-1C; Example 3).
Regarding claim 29
The method according to Stoeckius et al., wherein sample indexing sequences of at least 10, 100, or 1000 sample indexing compositions of the plurality of sample indexing compositions comprise different sequences (see page 17, paragraph 1).
Regarding claim 30
The method according to Stoeckius et al., wherein the sample indexing oligonucleotide comprises a second universal sequence (e.g., PCR handle. See Figure 1A).
Regarding claim 31
The method according to Stoeckius et al., wherein identifying the sample origin of the at least one cell comprises identifying the presence or absence of the sample indexing sequence of at least one extended sample indexing oligonucleotide, or product thereof, in the sequencing data (see page 43, lines 1-5; page 44, lines 12-19; paragraph bridging pages 46-47; page 49, lines 7-10; page 50, lines 22-27; Example 3).
Regarding claim 32
The method according to Stoeckius et al., wherein identifying the presence or absence of the sample indexing sequence comprises: amplifying the at least one extended sample indexing oligonucleotides, or products thereof, using a primer capable of hybridizing to the first universal sequence, or a complement thereof, and a primer capable of hybridizing to the second universal sequence, or a complement thereof, to generate a plurality of amplified extended sample indexing oligonucleotides; obtaining sequencing data of the plurality of amplified extended sample indexing oligonucleotides, or products thereof; and identifying the sample origin of the cell based on the sample indexing sequence of an amplified extended sample indexing oligonucleotide, or product thereof, of the plurality of amplified extended sample indexing oligonucleotides, or products thereof, that correspond to the at least one extended sample indexing oligonucleotide, or product thereof, in the sequencing data (see page 5, line 20 – page 6, line 20; paragraph bridging pages 44-45; paragraph bridging pages 47-48; page 49, line 11 – page 50, line 29; Example 3).
Regarding claim 33
The method according to Stoeckius et al., wherein amplifying the at least one extended sample indexing oligonucleotides, or products thereof, comprises attaching sequencing adaptors to the plurality of extended sample indexing oligonucleotides, or products thereof (see Example 3; Figure 1C).
Regarding claims 35-36
The method according to Stoeckius et al., wherein extending sample indexing oligonucleotides hybridized to the plurality of oligonucleotide barcodes comprises extending sample indexing oligonucleotides hybridized to the plurality of oligonucleotide barcodes using a DNA polymerase lacking at least one of 5' to 3' exonuclease activity and 3' to 5' exonuclease activity, wherein the DNA polymerase comprises a Klenow Fragment (see page 29, paragraph 1).
Regarding claims 37-38
The method according to Stoeckius et al., comprising removing unbound sample indexing compositions of the plurality of sample indexing compositions, wherein removing the unbound sample indexing compositions comprises washing the one or more cells from each of the plurality of samples with a washing buffer (see Figure 1C; Example 3).
Regarding claim 40
The method according to Stoeckius et al., wherein the sample indexing oligonucleotide is configured to be detachable from the cellular component-binding reagent (see page 4, lines 9-19; page 22, lines 1-2).
Regarding claim 41
The method according to Stoeckius et al., comprising dissociating the sample indexing oligonucleotide from the cellular component-binding reagent (see page 45, lines 3-4).
Regarding claims 42-43
The method according to Stoeckius et al., wherein the target-binding region comprises a poly(dT) sequence, and wherein the sample indexing oligonucleotide comprises a poly(dA) region (see Figures 1A-1C; page 5, line 20 – page 6, line 7; paragraph bridging pages 47-48; page 49, line 11 – page 50, line 29; Example 3), wherein the sample indexing oligonucleotide comprises an alignment sequence adjacent to the poly(dA) region (e.g., part of the antibody barcode sequence that is adjacent to the poly(dA) region may serve as an alignment sequence).
Regarding claim 44
The method according to Stoeckius et al., wherein a sample of the plurality of samples comprises a plurality of cells, a plurality of single cells, a tissue, a tumor sample, or any combination thereof (see paragraph bridging pages 22-23).
Conclusion
12. No claim is allowed.
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/KAIJIANG ZHANG/Primary Examiner, Art Unit 1684
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