DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 December 2, 2025 has been entered.
Applicant’s amendment filed on December 2, 2025 is acknowledged and has been entered. Claim 3, 10-11 and 14 has been canceled. Claim 1 has been amended. Claims 1-2, 4-9, 12-13 and 15-16 are pending.
Claims 1-2, 4-9, 12-13 and 15-16 are discussed in this Office action.
All of the amendments and arguments have been thoroughly reviewed and considered but are not found persuasive for the reasons discussed below. Any rejection not reiterated in this action has been withdrawn as being obviated by the amendment of the claims. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
This action is made NON-FINAL.
Response to Arguments
Applicant’s arguments, see p 6-9, filed December 2, 2025, with respect to the obviousness rejection under 103 over Mitra in view of Pieprzyk have been fully considered and are persuasive. The grounds of rejection has been withdrawn.
Response to Arguments – Double Patenting rejections maintained
Applicant's arguments filed December 2, 2025 have been fully considered but they are not persuasive.
Applicant requested the double patenting rejection be held in abeyance until claim language was deemed otherwise allowable. The rejections are maintained because while the art rejection falls away for the reasons noted at the conclusion below, the claimed subject matter remains unpatentable in view of the claims as rejected under double patenting.
Previous Grounds of Rejection
Priority
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 61448547, 61462972, 61426208, 61398159, 61395850, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. While each of these priority documents include support for multiplex, universal adaptors or universal amplification and mutation detection, none of these priority documents include sufficient (or any) support for the inclusion of barcodes or barcode primers, or the inclusion of cancer or tumor or that polymorphic loci are associated with tumor or cancer. Therefore, as the priority documents of US Patent 8825412 and 61516996, for example, provide support, the claims are afforded an earliest priority of April 12, 2011.
Double Patenting
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.
Claim 1-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-16 of U.S. Patent No. 11,519,035 (‘035 patent). Although the claims at issue are not identical, they are not patentably distinct from each other because while the patents are not identical, they are drawn to very similar subject matter. The instant claims require tagging adaptors on to cell free DNA with universal tails, followed by amplification, introducing a barcode and sequencing tag and then sequencing the products. The final step of the method includes high throughput sequencing.
The claims differ in that the claims of the ‘035 patent include blood while the instant claims do not encompass blood samples. The claim limitations in dependent claims are nearly identical. Compare claim 1 of the instant claims to claim 1 of the ‘035 patent, for example. Compare instant claims 4-6 to claims 3-5 of ‘035 patent.
Therefore, while the claims are not the same, they are also not patentably distinct.
Claim 1-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 8-9, 12 and 18 of U.S. Patent No. 10,262,755 (‘755 patent). Although the claims at issue are not identical, they are not patentably distinct from each other because while the patents are not identical, they are drawn to very similar subject matter. The instant claims require tagging adaptors on to cell free DNA with universal tails, followed by amplification, introducing a barcode and sequencing tag and then sequencing the products. The final step of the method includes high throughput sequencing.
The claims differ in that the claims of the ‘755 patent focus on aneuploidy while the instant claims are focused on amplification within a streamline of steps of modification, preparation and amplification as described. The claim limitations in dependent claims are nearly identical. Compare claim 1 of the instant claims to claim 1 and 18 of the ‘755 patent, for example.
Therefore, while the claims are not the same, they are also not patentably distinct.
Claim 1-7 and 15-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 6-9, 22 of U.S. Patent No. 10,731,220 (‘220 patent). Although the claims at issue are not identical, they are not patentably distinct from each other because while the patents are not identical, they are drawn to very similar subject matter. The instant claims require tagging adaptors on to cell free DNA with universal tails, followed by amplification, introducing a barcode and sequencing tag and then sequencing the products. The final step of the method includes high throughput sequencing.
The claims differ in that the instant claims include a step of multiplexed amplification that is a higher level than the claims of the ‘220 patent. A higher level of multiplex, though, is encompassed by claims 6-9 of ‘220. The ‘220 patent includes universal and barcode sequences, amplification and high throughput sequencing. The ligation step is included in claim 3 of ‘220 and the multiplex sequencing is recited in claims 6-9 of ‘220.
Therefore, while the claims are not the same they are also not patentably distinct.
Claim 1-7 and 15-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 3-10 and 22 of U.S. Patent No. 10,538,814 (‘814 patent). Although the claims at issue are not identical, they are not patentably distinct from each other because while the patents are not identical, they are drawn to very similar subject matter. The instant claims require tagging adaptors on to cell free DNA with universal tails, followed by amplification, introducing a barcode and sequencing tag and then sequencing the products. The final step of the method includes high throughput sequencing.
The claims differ in that the instant claims include a step of multiplexed amplification that is a higher level than the claims of the ‘814 patent. A higher level of multiplex, though, is encompassed by claims 5-8 of ‘814. The ‘814 patent includes universal and barcode sequences, amplification and high throughput sequencing. The ligation step is included in claim 3 of ‘814 and the multiplex sequencing is recited in claims 5-8 of ‘814.
Therefore, while the claims are not the same they are also not patentably distinct.
Claim 1-2 and 6 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 3-8, 22 of U.S. Patent No. 10,557,172 (‘172 patent). Although the claims at issue are not identical, they are not patentably distinct from each other because while the patents are not identical, they are drawn to very similar subject matter. The instant claims require tagging adaptors on to cell free DNA with universal tails, followed by amplification, introducing a barcode and sequencing tag and then sequencing the products. The final step of the method includes high throughput sequencing.
The claims differ in that the instant claims include a step of multiplexed amplification that is a higher level than the claims of the ‘172 patent. A higher level of multiplex, though, is encompassed by claims 5-8 of ‘814. The ‘172 patent includes universal and barcode sequences, amplification and high throughput sequencing. The ligation step is included in claim 3 of ‘172 and the multiplex sequencing is recited in claims 5-8 of ‘172. Therefore, while the claims are not the same they are also not patentably distinct.
Therefore, while the claims are not the same they are also not patentably distinct.
New Grounds of Rejection
Information Disclosure Statement
The information disclosure statement (IDS) submitted on December 2, 2025 was filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Conclusion
The claims are free of the art in view of Applicant’s arguments over Mitra in view of Pieprzyk. In particular, Applicant’s argument "the patch PCR disclosed by Mitra is not applicable to multiplexed amplification of cell-free DNA molecules extracted from a plasma sample, which are fragmented and do not have defined ends" (p 6 of remarks) and the arguments regarding the related post-filing mention by a co-inventor of Mitra that "the methods disclosed in United States Patent Application Publication No.: 20100129874 are only applicable if the end of at least two nucleic acid sequences to which patches can be annealed are known. Thus, these methods are not applicable to capturing DNA fragments and circulating cell free DNA - i.e., situations in which the defining ends of the nucleic acid target sequences are unknown.") (p 7 of remarks, where the Mitra patent was previously published as 20100129874) were persuasive to overcome the rejection of record.
Further, while there are similar references cited on the IDS filed December 2, 2025 such as Deciu et al. (US 20130338933 A1; December 2013), which teach features of the method, as claimed, Deciu is not available as prior art due to the earliest priority date as noted above. There are additional references such as Sparks et al. (US Patent 10,308,981; June 2019) and Van Eijk (US 20130137587; May 2013) which teach aspects of the method but do not teach or suggest all aspects of the method as claimed and none of the prior art would properly combine with either Sparks or Van Eijk to teach or suggest all aspects of the method, as claimed. While Sparks teaches a coupling of multiplex analysis followed by universal amplification of plural loci, Sparks does not teach or suggest a target specific multiplex amplification step prior to, or followed by the universal amplification step. Instead, Sparks teaches generation of a plurality of ligation products through locus specific bridging oligonucleotides across a plurality of loci, followed by universal amplification. Van Eijk teaches universal amplification steps but does not teach a sample that includes cell free nucleic acids and does not teach multiplex amplification. There are no references, including Pieprzyk, which teach or suggest a method that includes a multiplex amplification step followed by a universal amplification reaction in cell free DNA samples, as claimed. Therefore, the claims are free of the art but stand rejected for other reasons.
Conclusion
No claims are allowed. All claims stand rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEPHANIE KANE MUMMERT whose telephone number is (571)272-8503. The examiner can normally be reached M-F 9:00-5:30.
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/STEPHANIE K MUMMERT/Primary Examiner, Art Unit 1637