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 .
Claim Rejections - 35 USC § 112
2. Claims 106-119 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.
A. Claim 106 recites the phrase “coupling the first capture domain of the oligonucleotide attached to the first site to the second capture domain of the capture probe adhered to the first site…” It is not clear, given the language of the claim and the client’s specification, how this language is intended to limit the instant method. The claim language reads as though the first capture domain of the oligonucleotide is coupled to the second capture domain of the capture probe that is already adhered to the first site (e.g., by some sort of adhesive as described in applicant’s specification on pg. 137), or is the capture probe adhered to the first site via the coupling itself (i.e., hybridization of the capture probes)? The scope of this limitation is unclear and therefore the claim is indefinite.
B. Claims 107-119 are rejected for being dependent on a previously rejected claim.
Double Patenting
3. 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 106 and 110-118 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. US 12497654. Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to the interactions of nucleotides between array features on a substrate.
Regarding claim 106, the claims 1 and 16 of the issued patent teach a method for determining the location of a feature in a spatial array, comprising:
A. A plurality of oligonucleotides on the substrate (i.e., the first set of features), wherein the oligonucleotides comprise a first spatial barcode and a capture domain.
B. A plurality of features on the substrate (i.e., the second set of features) comprising a third oligonucleotide, wherein the third oligonucleotides comprise a second spatial barcode and a second capture domain.
C. Determining a nucleotide sequence of the first spatial barcode, thereby determining the location of the oligonucleotide on the substrate.
D. Coupling (i.e., attaching) the first capture domain of the first oligonucleotide to the second capture domain of the second oligonucleotide, thereby producing a second capture probe (i.e., the second oligonucleotide) comprising the first spatial barcode of the first oligonucleotide and the second spatial barcode of the second oligonucleotide.
E. Determining the sequences of the first and second spatial barcodes, or complements thereof.
F. Associating the second spatial barcode of the second oligonucleotide with the first spatial barcode of the first oligonucleotide, thereby determining the location of the second feature on the spatial array.
The issued patent does not teach all of the limitations of instant claim 106 in a single claim. However, it would have been obvious to one having ordinary skill in the art to have modified the patent claims to combine these disclosed elements because they are all disclosed in the claims of the issued patent as preferred embodiments of the invention.
Regarding claim 110 of the instant application, claims 6, 7 and 10 of the issued patent teach performing an extension reaction or a splint mediated ligation reaction between the first and second oligonucleotides. “Coupling” or “attaching” during either of these techniques inherently comprises hybridization.
Regarding claim 111 of the instant application, claims 9, 111 and 112 of the issued patent teach determining all of the sequence of the nucleic acid product or complement thereof by sequencing.
Regarding claim 112 of the instant application, claim 12 of the issued patent teaches determining all of the sequence of the nucleic acid product or a complement thereof using sequencing by ligation. The sequencing by ligation technique inherently comprises the sequencing template comprising a constant sequence for initiating a sequencing reaction.
Regarding claim 113 of the instant application, claim 12 of the issued patent teaches determining all of the sequence of the nucleic acid product or a complement thereof using sequencing by ligation. The sequencing by ligation technique inherently comprises hybridizing a sequencing anchor to a constant sequence prior to hybridizing a sequencing probe to the sequence for initiating a sequencing reaction.
Regarding claim 114 of the instant application, claims 9, 111, 112 of the issued patent teach determining all of the sequence of the nucleic acid product or complement thereof by sequencing.
Regarding claim 115 of the instant application, claim 12 of the issued patent teaches determining all of the sequence of the nucleic acid product or a complement thereof using sequencing by ligation. The sequencing by ligation technique inherently comprises the sequencing template comprising a constant sequence for initiating a sequencing reaction.
Regarding claim 116 of the instant application, claim 12 of the issued patent teaches determining all of the sequence of the nucleic acid product or a complement thereof using sequencing by ligation. The sequencing by ligation technique inherently comprises hybridizing a sequencing anchor to a constant sequence prior to hybridizing a sequencing probe to the sequence for initiating a sequencing reaction.
Regarding claim 117 of the instant application, claim 8 of the issued patent teaches that the second oligonucleotide is cleaved from the second feature (i.e., comprises a cleavage domain).
Regarding claim 118 of the instant application, claim 8 of the issued patent teaches performing an extension reaction with the first oligonucleotide and the second oligonucleotide.
Claims 107-109 and 119 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. US 12497654 in view of Zhou (US Patent Application No. US 20160303534 A1, published 2016-10-20) and So (International Patent Application No. WO 2017019456 A2, published 2017-02-02).
The limitations of claims 107-109 and 119 are not disclosed in the issued patent.
However, Zhou does teach that the recipient surface is a bead as discussed above, and So teaches a patterned surface wherein the pattern is a random arrangement of features ([00103]) and that features are beads (00112]). A person having ordinary skill in the art would have understood that the generic recipient bead surface taught by Zhou could simply be substituted with the random arrangement of beads taught by So to arrive at the instantly claimed invention with a reasonable expectation of success. One having ordinary skill in the art would have recognized the advantages of using a bead array as the recipient surface, as bead surfaces are well known to provide a higher oligonucleotide packing density compared to planar surfaces (See Grigoryev) In addition, it would have been obvious to the ordinary artisan that the known techniques in the cited references could have been combined with predictable results. The method taught by Zhou modified in view of So would result in a transfer array (i.e., the substrate of the claim) hybridized to a recipient array (i.e., the random bead array of So). When the two arrays are hybridized within the method, the features of the random bead array are affixed via hybridization to the transfer surface. It is noted that this combination teaches a spatial array comprising a substrate, wherein the substrate comprises oligonucleotides on the substrate (corresponding to claim 106 step (a)(i)) and a recipient array that is a plurality of features randomly arranged on the substrate (corresponding to claim 106 step (a)(ii)).
Regarding claim 107, Zhou teaches that the recipient surface is a bead ([0123]) and So teaches an array of features on a substrate, where the features are beads ([00112]).
Regarding claim 108 and 109, Zhou teaches a second surface comprising primers (i.e., the second capture domain [0003]) and that primers are polyT DNA ([0124]). Zhou also teaches that these primers bind to template nucleic acids (i.e., first oligonucleotides on the template array [0005]). It is an inherent property of polyT DNA to be complementary to a region of polyA DNA.
Regarding claim 119, So teaches that each capture probe includes a unique spatial address sequence (i.e., a unique barcode; [0085]).
It would have been obvious to modify the claims of the issued patent to include these limitations. An ordinary artisan would have been motivated to make these modifications because Zhou’s teachings provide additional advantages in copying array features from one substrate to another, allowing for the repeatable generation of array surfaces on different substrates while correlating the location of features between each surface. So’s teachings provide additional advantage of describing the characteristics of bead arrays, which are known in the art to provide a higher oligonucleotide packing density compared to planar surfaces. In addition, it would have been obvious to one of ordinary skill in the art that the known techniques of the cited references could have been combined with the claims of the issued patent with predictable results, because all of the techniques relate to the synthesis of oligonucleotide arrays on various substrates.
Response to Arguments
4. With regard to the rejection of claims 106-119 under U.S.C. 103, applicant argues that the combination of Zhou, So and Grigoryev fail to teach the elements of the amended claim wherein a second capture probe is produced, comprising the first spatial barcode of the oligonucleotide and the second spatial barcode of the capture probe, wherein the first spatial barcode and the second spatial barcode comprise different sequences (see applicant’s remarks, pg. 6 ¶ 4).
While the combination of Zhou, So and Grigoryev do make obvious a plurality of features (e.g., beads) randomly affixed to a substrate, that the features comprise capture probes which comprise barcodes, and the substrate comprises barcoded oligonucleotides, applicant’s arguments set forth on 29 October 2025 that “Zhou does not contemplate an array in which the template oligonucleotide and its corresponding recipient oligonucleotide… have different barcodes,” and that the secondary references do not cure this deficiency, are persuasive (pg. 6-8 of applicant’s remarks).
Regarding the double patenting rejection, the response requests that the examiner hold the provisional rejection in abeyance until otherwise allowable subject matter is identified in the instant application. However, a complete response to a nonstatutory double patenting (NSDP) rejection is either a reply by applicant showing that the claims subject to the rejection are patentably distinct from the reference claims or the filing of a terminal disclaimer in accordance with 37 CFR 1.321 in the pending application(s) with a reply to the Office action (see MPEP § 1490 for a discussion of terminal disclaimers). Such a response is required even when the nonstatutory double patenting rejection is provisional. As filing a terminal disclaimer, or filing a showing that the claims subject to the rejection are patentably distinct from the reference application’s claims, is necessary for further consideration of the rejection of the claims, such a filing should not be held in abeyance. MPEP §804(I)(b)(1). For the reasons set forth above and those already of record, the provisional nonstatutory double patenting rejection in view of application 17612625 has been converted to a non-provisional rejection in view of United States Patent US 12497654, is modified to address the amended claims, and maintained.
The provisional NSDP rejection in view of application 17312615 has been withdrawn as the reference application has been abandoned.
Conclusion
5. Voelkerding et al. Next-Generation Sequencing: From basic research to Diagnostics, Clinical Chemistry, 55(4), 641-658, 2009-04-01 teach sequencing by ligation. See Figure 3 on page 646, primer n is a sequencing anchor and the interrogation probe is a sequencing probe.
6. No claims are allowed.
7. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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/BRIAN ELLIS YOUNG/ Examiner, Art Unit 1684
/JULIET C SWITZER/Primary Examiner, Art Unit 1682