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. OBJECTIONS 2. The specification is objected to because of the following informality: the continuation information must be updated to indicate abandonment of the parent ‘813 application. 3. Applicant is reminded of the proper content of an abstract of the disclosure. A patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains . The abstract should not refer to purported merits or speculative applications of the invention and should not compare the invention with the prior art. If the patent is of a basic nature, the entire technical disclosure may be new in the art, and the abstract should be directed to the entire disclosure. If the patent is in the nature of an improvement in an old apparatus, process, product, or composition, the abstract should include the technical disclosure of the improvement. The abstract should also mention by way of example any preferred modifications or alternatives. Where applicable, the abstract should include the following: (1) if a machine or apparatus, its organization and operation; (2) if an article, its method of making; (3) if a chemical compound, its identity and use; (4) if a mixture, its ingredients; (5) if a process, the steps . Extensive mechanical and design details of an apparatus should not be included in the abstract. The abstract should be in narrative form and generally limited to a single paragraph within the range of 50 to 150 words in length. See MPEP § 608.01(b) for guidelines for the preparation of patent abstracts. NON-PRIOR ART REJECTIONS 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 appl icant regards as his invention. Claim 4 is 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. This claim is indefinite because the language ‘comprising at a plurality of amplicons within the specific target locus,’ near the beginning of part (ii) is an incomplete phrase, and thus it cannot be determined what is encompassed. Correction is required. 5. The following is a quotation of the first paragraph of 35 U.S.C. 112(a): (a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention. The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112: The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention. Claims 5-7 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, as failing to comply with the written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Independent claim 5 recites, toward the beginning of part ( i ), and near the end of part (ii), ‘primer groups ’ . No support has been found in the specification for this language; thus, the claims comprise new matter. If this rejection is traversed, it is requested that support in the specification be pointed to with particularity, as in page, paragraph, or line numbers. 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. Claim s 2-3 are rejected on the ground of nonstatutory double patenting a s being unpatentable over claim s 1 and 3 of U.S. Patent No. 10,316,359 . Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims and the pending claims are related as genus-obvious species . That is, the pending claims add the additional limitation that ‘the 3’ complementary sequence is unique and non-repetitive with respect to the nucleic acid substrate’, and one of ordinary skill in the art considering the patented claims would have been motivated to use such a 3’ complementary sequence in the patented methods because this would have merely followed from straightforward, logical scientific reasoning . As one of ordinary skill was well aware, such unique, non-repetitive target sequences avoid the problem of non-specific binding to multiple undesirable sequences, which compromises the usefulness of results . It would have been prima facie obvious to one of ordinary skill in the art considering the patented methods to carry out the pending methods. 8. Claim s 4-7 are rejected on the ground of nonstatutory double patenting a s being unpatentable over claim s 1 and 3 of U.S. Patent No. 10,316,359 in view of Gardner et al. (2014) . The patented claims and the pending claims are related as genus-obvious species . That is, the pending claims add additional limitations regarding sequencing a next generation sequencing library and ligating sequencing adaptors to amplicons, which was conventional in the art of sequencing. Gardner teaches the application of multiplex amplification to generating next generation sequencing libraries for deep sequencing. See especially ‘MHV Results’ and ‘Conclusions’ on page 7. O ne of ordinary skill in the art considering the patented claims would have been motivated to use the resulting amplicons in next generation sequencing applications because Gardner taught using multiplex amplicons to generate sequencing libraries to generate sequencing information. It would have been prima facie obvious to one of ordinary skill in the art considering the patented methods and Gardner to carry out the pending methods. 9. Claims 2-3 are rejected on the ground of nonstatutory double patenting a s being unpatentable over claim 14 of U.S. Patent No. 11,203,781 . Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims and the pending claims are related as genus-obvious species . That is, the pending claims add the additional limitation that ‘the 3’ complementary sequence is unique and non-repetitive with respect to the nucleic acid substrate’, and one of ordinary skill in the art considering the patented claims would have been motivated to use such a 3’ complementary sequence in the patented methods because this would have merely followed from straightforward, logical scientific reasoning . As one of ordinary skill was well aware, such unique, non-repetitive target sequences avoid the problem of non-specific binding to multiple undesirable sequences, which compromises the usefulness of results . It would have been prima facie obvious to one of ordinary skill in the art considering the patented methods to carry out the pending methods. 10. Claims 4-7 are rejected on the ground of nonstatutory double patenting a s being unpatentable over claims 6-7 of U.S. Patent No. 11,203,781 . Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims and the pending claims are related as species -genus . That is, the steps and limitations within the pending claims are also within the steps and limitations of the patented claims, and the patented claims require the additional limitations that the target locus is a gene known to have clinical relevance in oncology. Thus, the patented claims are a species within the broader pending claims. PRIOR ART REJECTION 11. 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. 12. 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. 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. 13. Claim s 2-7 are rejected under 35 U.S.C. 103 as being unpatentable over Gardner et al. (2014) in view of Lao et al. (US 2009/029 1475). Regarding independent claims 2, 4, and 5, Gardner teaches methods of multiplex PCR amplification, and that because primers of overlapping regions can also produce amplicons shorter than the desired amplicon, it is advantageous to include a step of removing short amplicons before sequencing. See pages 1-7, especially pages 4 and 6-7. Gardner does not teach removing undesirable short amplicons from a multiplex PCR reaction by using self-hybridizing primer sequences. Lao discloses the use of self-hybridizing primer sequences to selectively amplify longer amplicons over shorter amplicons, based on shorter amplicons forming secondary structure via self-hybridization, thus preventing undesirable amplification. See paragraphs 0003, 0069, 0116, and 0166. One of ordinary skill in the art would have been motivated to modify the method of Gardner by selecting against short amplicons using self-hybridizing primer sequences resulting in short amplicons which form secondary structure, because such a means for selecting against short amplicons was disclosed by Lao. It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to carry out the claimed methods. Regarding claim 3, 3’ complementary sequence of between 16 and 30 bases in length would have been determined merely by routine optimization of known-important reaction parameters, which as well established in U.S. patent practice does not support unobviousness (M.P.E.P. 2144.05). Regarding claims 4-7, Gardner teaches using multiplex amplification to produce a sequencing library and performing sequencing with said library, and this process conventionally involved ligation of 3’ and 5’ sequencing adaptors to library amplicons to facilitate sequencing reactions. Further regarding claim 7, sequence coverage of greater than 20% of a mean per base would have been achieved merely through routine optimization. CONCLUSION 14. No claims are free of the prior art. 15 . Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT KENNETH R HORLICK whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-0784 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT Mon. - Thurs. 8:30 - 6:30 . Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, FILLIN "SPE Name?" \* MERGEFORMAT Gary Benzion can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT 571-272-0782 . The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. 03/03/26 /KENNETH R HORLICK/ Primary Examiner, Art Unit 1681