FINAL ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This action is responsive to the Amendment/Response to Office Action filed 06 May 2026. Claims 5-6, 8-9, and 13-20 have been amended and claims 7 and 11-12 have been canceled. All prior rejections of claims 7 and 11-12 are moot in view of the cancelation of those claims. Claims 1-4 remain withdrawn (see also paragraphs 5-6 below), and claims 5-6, 8-9, and 13-20 remain under consideration herein. Applicant’s amendments and arguments have been thoroughly reviewed, and have overcome the following objections/rejection set forth in the prior Office action:
The objection to claim 10, in view of Applicant’s amendment correcting a typographical error;
The prior rejections of claims under 35 USC 112(b)/second paragraph in view of Applicant’s amendments (although it is noted that the amended claims are indefinite for the reasons given below);
The rejections under 35 USC 112(d)/fourth paragraph, in view of Applicant’s amendment rendering claim 5 an independent claim, and amendment of claims 13-15 to depend from claim 5;
The rejection of claim 5 and claims dependent therefrom under 35 USC 102(a)(1) and 35 USC 102(a)(2) as being anticipated by Hoon et al in view of Applicant’s amendment of claim 5 to require that the claimed nucleic acid probe comprise “a 3’ end and/or a 5’ end that is covalently linked to at least one detectable label”; and
The rejection of claims 5, 10, and 13-15 under 35 USC 101 in view of Applicant’s amendments to claim 5 (such that a 3’ and/or 5’ end of the claimed probe must be covalently linked to at least one detectable label);
Claims 5-6, 8-10, and 13-20 remain rejected for the reasons given below, which include new grounds of rejection necessitated by Applicant’s amendments. Any rejections and/or objections not reiterated in this action have been withdrawn. This action is FINAL.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Election/Restrictions
Applicant's election with traverse of Group II in the reply filed on 06 January 2026 is again acknowledged.
Claims 1-4 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 09 January 2026.
Claim Interpretation
Regarding amended claims 6 and 17, it is noted that the language “wherein the 3’ and the 5’ ends are covalently linked to a total of at least three detectable labels” has been interpreted as requiring that the combined total number of labels linked to the 3’ and 5’ ends is at least three (i.e., the claim does not require that at least three labels be attached to each end of the probe).
Claim Rejections - 35 USC § 112(b)/second paragraph
THE FOLLOWING INCLUDES NEW GROUNDS OF REJECTION NECESSITATED BY APPLICANT’S AMENDMENTS:
Claims 5-6, 8-10, and 13-20 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.
Claims 5-6, 8-10, and 13-15 are indefinite over the recitation in amended independent claim 5 of the limitation “A nucleic acid probe hybridized to cell-free DNA (cfDNA), wherein the nucleic acid probe comprises…..and the cfDNA is not amplified prior to hybridizing with the nucleic acid probe”, because it is unclear how the cfDNA recited in the claim – which is not part of the claimed invention based on the present wording of the claims – further limits the characteristics of the claimed probe. In particular, it is noted that the claim as written is directed to “A nucleic acid probe”, not, e.g., a composition comprising or consisting of a “nucleic acid probe hybridized to cell-free DNA (cfDNA)….”, such that the cfDNA is not itself a requirement of the product claimed; thus, interpretation of the claim requires an understanding of how the form of the probe is or is not modified by this claim language. As the inherent sequence/ structure of such a probe would be unaltered by hybridization, some persons of skill in the art would interpret the references in the claim to cfDNA as being completely non-limiting of what is claimed; however, this language may also be interpreted as an attempt to require some type of more particular structure for the claimed probe (but lacking clear limitations on what that structure might be), and/or an attempt to limit the environment of the probe (which also creates confusion regarding what the actual limitations of the claimed product are). Accordingly, further clarification is needed. Given this lack of clarity, it is noted that for purposes of further examination, claim 5 has been interpreted as simply requiring a nucleic acid probe meeting the length and sequence/structure requirement specified in the claim, and “a 3’ end and/or 5’ end that is covalently linked to at least one detectable label” (as this is one reasonable interpretation of the present claim language).
Claims 16-20 are indefinite over the recitation in amended independent claim 16 of the limitation “A nucleic acid probe hybridized to a nucleic acid from a biofluidic sample, wherein the nucleic acid probe comprises…..and the nucleic acid from the biofluid sample is not amplified prior to hybridizing with the nucleic acid probe”, because it is unclear how the “nucleic acid from a biofluidic sample” recited in the claim – which is not part of the claimed invention based on the present wording of the claims – further limits the characteristics of the claimed probe. In particular, it is noted that the claim as written is directed to “A nucleic acid probe”, not, e.g., a composition comprising or consisting of a “nucleic acid probe hybridized to” another nucleic acid, such that the “nucleic acid from a biofluidic sample” is not itself a requirement of the product claimed; thus, interpretation of the claim requires an understanding of how the form of the probe is or is not modified by this claim language. As the inherent sequence/ structure of such a probe would be unaltered by hybridization, some persons of skill in the art would interpret the references in the claim to the “nucleic acid from a biofluidic sample” as being completely non-limiting of what is claimed; however, this language may also be interpreted as an attempt to require some type of more particular structure for the claimed probe (but lacking clear limitations on what that structure might be), and/or an attempt to limit the environment of the probe (which also creates confusion regarding what the actual limitations of the claimed product are). Accordingly, further clarification is needed. Given this lack of clarity, it is noted that for purposes of further examination, claim 16 has been interpreted as simply requiring a nucleic acid probe comprising SEQ ID NO: 2 covalently linked to a detectable label (as this is one reasonable interpretation of the present claim language).
Claim Rejections - 35 USC § 103
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.
THE FOLLOWING INCLUDES NEW GROUNDS OF REJECTION NECESSITATED BY APPLICANT’S AMENDMENTS:
Claim(s) 5, 9-10, and 13-15 are rejected under 35 U.S.C. 103 as being unpatentable over Hoon et al (John Wayne Cancer Institute, WO 2006/128192 A2 [30 Nov 2006]; cited in IDS) in view of the Plant-Microbe Genomics Facility (PMGF) at The Ohio State University (hereinafter “OSU”) (“Procedures and Recommendations for Quantitative PCR”, version 1.2 [April 2003]; previously cited).
It is reiterated that independent 5 as amended has been interpreted as requiring
a nucleic acid probe meeting the length and sequence/structure requirement specified in the claim – i.e., a probe comprising “at least 20-180 contiguous nucleotides complementary to SEQ ID NO: 1” - and “a 3’ end and/or 5’ end that is covalently linked to at least one detectable label”.
Hoon et al teach methods comprising detection of “free circulating” DNA (a.k.a. cell-free DNA) in body fluids, which methods include targeting Alu sequences in the cfDNA to determine the amount thereof (see entire reference, particularly the Summary at page 1-4). Instant SEQ ID NO: 1 shares 100% identity with the consensus human Alu sequence of Hoon et al, as depicted below (see also Figures 1, 6A and 11A of Hoon et al):
Query Match 100.0%; Score 290; Length 290;
Best Local Similarity 100.0%;
Matches 290; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGCGGA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 GGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGCGGA 60
Qy 61 TCACCTGAGGTCAGGAGTTCGAGACCAGCCTGGCCAACATGGTGAAACCCCGTCTCTACT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 TCACCTGAGGTCAGGAGTTCGAGACCAGCCTGGCCAACATGGTGAAACCCCGTCTCTACT 120
Qy 121 AAAAATACAAAAATTAGCCGGGCGTGGTGGCGCGCGCCTGTAATCCCAGCTACTCGGGAG 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 AAAAATACAAAAATTAGCCGGGCGTGGTGGCGCGCGCCTGTAATCCCAGCTACTCGGGAG 180
Qy 181 GCTGAGGCAGGAGAATCGCTTGAACCCGGGAGGCGGAGGTTGCAGTGAGCCGAGATCGCG 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GCTGAGGCAGGAGAATCGCTTGAACCCGGGAGGCGGAGGTTGCAGTGAGCCGAGATCGCG 240
Qy 241 CCACTGCACTCCAGCCTGGGCGACAGAGCGAGACTCCGTCTCAAAAAAAA 290
||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 CCACTGCACTCCAGCCTGGGCGACAGAGCGAGACTCCGTCTCAAAAAAAA 290
With particular regard to nucleic acid probes encompassed by claim 5, Hoon et al disclose methods comprising obtaining any body fluid sample (see, e.g., page 3 at line 19; page 11 at line 15), and detecting and quantitating the cfDNA therein via the use of microarrays, “probes by blotting”, etc., with a preferred method being qPCR, particularly employing fluorogenic probes detectably labeled with a fluorophore and quencher (see entire reference, particularly, e.g., pages 11-12). Among the preferred nucleic acid amplification products taught by Hoon et al are ALU247 and ALU115 PCR products (see, e.g., pages 15-17, the Examples, and Figures 6A and 11A), which products are produced via amplification using primer pairs depicted on pages 22 (regarding the 115 base pair amplicon ALU115) and 29 (regarding both the 115 base pair amplicon ALU115 and the 247 base pair amplicon ALU247). The reverse ALU115 primer disclosed by Hoon et al is 20 nucleotides in length and complementary to instant SEQ ID NO: 1, and thus meets the length and sequence/structure requirements of the claimed probe of instant claim 5; additionally both PCR products disclosed by Hoon et al inherently include nucleic acid probes complementary to instant SEQ ID NO: 1, and thus also meet the length and sequence/structure requirements of claims 5 and 13 (with the ALU115 product also including a complement meeting the length requirement of claim 13 (but too long in length to meet the requirements of claims 10, 14, and 15).
Hoon et al, while teaching a preferred method of qPCR, particularly employing fluorogenic probes detectably labeled with a fluorophore and quencher (see entire reference, particularly, e.g., page 12), as well as primers meeting the length requirements of claim 5 (as noted above), fail to explicitly teach probes labeled “wherein the 3’ or the 5’ ends are covalently linked to a detectable label”, as required by amended independent claim 5 (as well as claim 9, which recites a linked “fluorescent molecule”). Additionally, Hoon et al do not teach Alu amplification products meeting the length requirements of claims 10, 14, and 15 (which products would inherently include a type of probe meeting the requirements of these claims), and do not otherwise teach probes meeting the length requirements of claim 10, 14, and 15.
OSU provides detailed guidance regarding the performance of quantitative PCR (i.e., the preferred methodology of Hoon et al noted above) to achieve quantitation of a target sequence of interest (see entire reference, particularly pages 1-4). OSU teaches that in qPCR as recited by Hoon et al - which is taught by Hoon et al as employing a fluorogenic probe that “is an oligonucleotide with both a reporter fluorescent dye and a quencher dye attached” in a method in which during “the extension phase of PCR….the probe anneals downstream from one of the primer sites and is cleaved by the 5’ nuclease of Taq DNA polymerases” resulting in separation of reporter dye from quencher (Hoon et al p. 12) – the probes “have a dye at each end of the oligonucleotide” (i.e., a dye at the 5’ end and at the 3’ end) (see in particular pages 2-3 of OSU). OSU further teach that in such qPCR the target amplicon size is 75-150 bases (see pages 3-4).
In view of the teachings of OSU, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have employed in qPCR as taught by Hoon et al a fluorogenic probe in which the fluorophore and quencher were covalently linked to the 5’ and 3’ ends of the probe. Given the lack of specific guidance provided by Hoon et al, an ordinary artisan would have looked to the teachings of the prior art – such as OSU - for additional guidance needed to successfully implement the methods of Hoon et al, and as a result of modifying Hoon et al in view of OSU, would have prepared probes labeled in the manner required by the claims. An ordinary artisan would have taken this approach simply for the advantage of efficiency and convenience in implementing the teachings of Hoon et al (as compared to experimenting to identify appropriate types/manner of labeling, etc.) Additionally, given the detailed guidance provided by OSU, an ordinary artisan would have had a reasonable expectation of success in preparing such labeled probes. With further regard to claim 9, it is noted that both Hoon et al and OSU teach the use of fluorescent molecules as labels in such methods.
With further regard to claims 10, 14, and 15, it also would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have - when performing/implementing a qPCR targeting the Alu sequence disclosed by Hoon et al in the manner suggested by the teachings of Hoon et al in view of OSU, as indicated above – designed primers and a probe for amplification and detection of an amplicon 75-150 base pairs in length, simply because this is the preferred amplicon size taught by OSU for such methods (see again page 3 bridging to page 4). Again, one of ordinary skill in the art would have recognized a benefit in the efficiency and convenience provided by following specific prior art teachings regarding implementation of qPCR regarding a target of interest, and would have had a reasonable expectation of success in implementing such a modification given the detailed guidance provided by OSU. The teachings of Hoon et al in view of OSU suggest any of a range of different amplicons 75-150 base pairs in length – meeting the length requirements of claims 10, 14, and 15 – any of which would have contained a nucleic acid functional as a probe complementary to instant SEQ ID NO: 1, and thus meeting the requirements of the claims. While each of claims 10, 14, and 15 recites a narrower range of lengths falling within the range suggested by the cited art (with claim 10 reciting a specific length within this range), it is noted that - as discussed in MPEP 2144.05(I) – where a claimed range overlaps or lies inside a range disclosed by the prior art, a prima facie case of obviousness exists. Thus, absent, e.g., a showing of unexpected results, the probes of the claims are obvious over the teachings of Hoon et al in view of OSU (see MPEP 2144.05(III)).
It is noted that the Reply of 06 May 2026 provides a combined traversal of all rejections under 35 USC 103; these arguments are addressed below following all 103 rejections.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Hoon et al in view of OSU as applied to claims 5, 9-10, and 13-15, above, and further in view of Ryazantsev et al (Analyst 139:2867 [2014]; previously cited).
The teachings of Hoon et al and OSU are set forth above. While Hoon et al in view of OSU suggest ‘fluorogenic” probes labeled 5’ and 3’, neither Hoon et al nor OSU teaches probes “covalently linked to at least three detectable moieties”, as required by claim 6. Ryazantsev et al teach an alternative types of fluorogenic probes usable in qPCR, molecular beacons, and teach a variety of different labeling schemes suitable for qPCR (see entire reference, particularly the Abstract, Table 1, and Figure 2). Among the alternatives taught by Ryazantsev et al are probes including three total detectable moieties at the 3’ and 5’ ends (meeting the requirements of claim 6); see, e.g., MB13 and MB14 as depicted in Fig 2 (and see also Table 1). Ryazantsev et al teach that MB14 “has a very high signal/background ratio in fluorescent melting” and “allows maximizing the fluorogenic effect in real-time PCR” (see “Conclusion”, page 2872, left column). In view of the teachings of Ryazantsev et al, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the methods suggested by Hoon et al in view of OSU so as to have prepared and employed a probe labeled in the manner taught by Ryazantsev et al, and thereby to have prepared a probe meeting the requirements of claim 6. An ordinary artisan would have been motivated to have made such a modification for the benefits taught by Ryazantsev et al of superior signal/background ratio and “maximizing the fluorogenic effect” when performing qPCR. Further, an ordinary artisan would have had a reasonable expectation of success in making such a modification given the teachings and guidance provided by Hoon et al, OSU, and (with particular regard to a labeling scheme as required by the claim) Ryazantsev et al.
It is again noted that the Reply of 06 May 2026 provides a combined traversal of all rejections under 35 USC 103; these arguments are addressed below following all 103 rejections.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Hoon et al in view of OSU as applied to claims 5, 9-10, and 13-15, above, and further in view of Reischl et al (Molecular Biotechnology 3:55 [1995]; previously cited).
The teachings of Hoon et al and OSU are set forth above. While Hoon et al in view of OSU suggest the use of probes labeled 5’ and 3’ in qPCR, neither Hoon et al nor OSU teaches probes in which a detectable moiety is biotin, as required by claim 8.
Reischl et al provide an overview of qPCR (see entire reference), including teachings related to various known and usable labeling procedures (see in particular section 3.1 at pages 60-61). Reischl et al teach that while radioactive labels were initially commonly employed in PCR, “a variety of highly sensitive nonradioactive indicator systems” were developed due to the difficulties presented in handling radioactive labels (page 60, right column). Among the alternative label types taught by Reischl et al is biotin (page 60, right column), and Reischl et al teach that biotin may be incorporated into PCR products in multiple different ways, including via the end labeling (page 60, right column). Reischl et al also teach that PCR products may be “double labeled” with biotin and other labels, with the presence of biotin allowing capture via streptavidin (see section 3.2.3 “Solid-Phase Assays”, pages 62-63). In view of the teachings of Reischl et al, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the methods suggested by Hoon et al in view of OSU so as to have prepared and employed a probe end-labeled with biotin (including in combination with other labels, as required by the claims). An ordinary artisan would have been motivated to have made such a modification for the benefit of facilitating capture/detection of nucleic acids/amplicons via streptavidin, as taught by Reischl et al. Additionally and/or alternative, an ordinary artisan would have recognized such a modification as the simple substitution of one known, prior art label type for another, facilitating the predictable result of detecting a qPCR product (via any preferred method of qPCR; while it is noted that the claims recite a ”nucleic acid probe”, primers as taught by the cited art are also types of probes that function in both amplification and detection of target sequences of interest). Further, an ordinary artisan would have had a reasonable expectation of success in making such a modification given the teachings and guidance provided by Hoon et al, OSU, and (with particular regard to a labeling scheme as required by the claim) Reischl et al.
The Reply of 06 May 2026 traverses the prior rejections of claims under 35 USC 103 on the following grounds.
The Reply summarizes the requirements of a proper obviousness rejection (Reply page 8), and argues that the amendment of independent claim 5 to require a “nucleic acid probe hybridized to cell-free DNA (cfDNA), wherein…the cfDNA is not amplified prior to hybridizing with the nucleic acid probe” is sufficient to overcome all rejections under 35 USC 103, particularly urging that “Hoon does not disclose cfDNA hybridizing with a nucleic acid probe without prior amplification”, and that none of the cited references or combinations thereof “disclose or suggest all the features recited in amended claim 5” (Reply pages 8 bridging to page 9).
These arguments have been thoroughly considered but are not persuasive. As discussed above, amended claim 5 is indefinite, and the claim as written only clearly requires the “nucleic acid probe”; the manner in which the cfDNA of the claim relates to (and potentially alters) the claimed probe is not clear. Thus, the recited cfDNA (which is not clearly required by the present claim language) and its features/characteristics cannot be relied upon in the manner argued by Applicant. 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).
Double Patenting
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
THE FOLLOWING INCLUDES NEW GROUNDS OF REJECTION NECESSITATED BY APPLICANT’S AMENDMENTS:
Claims 16 and 20 are rejected under 35 U.S.C. 101 as claiming the same invention as that of claims 1 and 5, respectively, of prior U.S. Patent No. 11,926,868 (cited in IDS). This is a statutory double patenting rejection.
It is reiterated that the claims are indefinite for the reasons given above, and that claim 16 has been interpreted as simply requiring a nucleic acid probe comprising SEQ ID NO: 2 covalently linked to a detectable label. Dependent claim 20 further requires that “the detectable label is a fluorescent molecule”. Further, the terms “detectable label” and “detectable moiety” have been interpreted as equivalent to one another.
‘868 claim 1 is drawn to a “nucleic acid probe for detecting an Alu nucleic acid sequence in a nucleic acid from a biofluidic sample, comprising the nucleic acid sequence of SEQ ID NO: 2 covalently linked to a detectable moiety”, while its dependent claim 5 further requires that “the detectable moiety is a fluorescent molecule”. It is noted that SEQ ID NO: 2 of the ’868 patent (which issued from the parent application of the instant application) is identical to instant SEQ ID NO: 2, such that the instant claims and the ‘868 claims are directed to nucleic acid probes identical in structure to one another (and this applies both with regard to instant claim 16 as compared to ‘868 claim 1, and instant claim 20 as compared to ‘868 claim 5). While the instant claims and the ‘868 claims contain differences in wording, these differences do not clearly and necessarily impart any further structural requirements on the claimed products, which are defined via the recitation of specific sequences (SEQ ID NO: 2) and a required covalently linked detectable label/moiety (which is the case of the dependent claims must be a “fluorescent molecule”). Thus, instant claims 16 and 20 claim the same invention as ‘868 claims 1 and 5, respectively.
The Reply of 06 May 2026 traverses the rejection on the grounds that the amendment of claim 16 to recite “in part, a nucleic acid probe hybridized to a nucleic acid from a biofluidic sample” renders the instant claims “directed to a different invention”. However, this argument is nonpersuasive because the instant claims remain rejected to a “nucleic acid probe”, and the new claim language does not clearly differentiate the invention of the instant claims from that of the ‘868 claims.
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.
THE FOLLOWING INCLUDES NEW GROUNDS OF REJECTION NECESSITATED BY APPLICANT’S AMENDMENTS:
Claims 16-20 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 11,926,868 (cited in IDS). Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons. (Please see also the statutory double patenting rejection above that applies to instant claims 16 and 20; those claims are also included herein as they are also not patentably distinct from the other claims of the ‘868 patent).
Regarding instant claims 16-20, claim 16 (from which claims 17-20 depend) has been interpreted (as discussed above) as being directed to a nucleic acid probe comprising SEQ ID NO: 2 covalently linked to a detectable label. ‘868 claim 1 is drawn to a “nucleic acid probe for detecting an Alu nucleic acid sequence in a nucleic acid from a biofluidic sample, comprising the nucleic acid sequence of SEQ ID NO: 2 covalently linked to a detectable moiety”, while its dependent claim 5 further requires that “the detectable moiety is a fluorescent molecule”. It is again noted that SEQ ID NO: 2 of the ’868 patent (which issued from the parent application of the instant application) is identical to instant SEQ ID NO: 2. Thus, the sequence/structure of the nucleic acid of the instant claims is identical to that of the ‘868 claims, with the instant claims merely reciting different labeling schemes as compared to the ‘868 claims (such that the claimed inventions are not identical, other than instant claim 16 and ‘868 claim 1, and instant claim 20 and ‘868 claim 5). Given that the ‘868 claims recite both 3’ and 5’ labeling with a “detectable moiety” as well as multiple such moieties, and further recite the same preferred such moieties as the instant claims (biotin and a “fluorescent molecule), the instant claims are not patentably distinct from the ‘868 claims. In some cases the ‘868 claims anticipate the instant claims (for example, ‘868 claims 2-3 are preferred embodiment embraced by instant claim 18, with ‘858 claims 4 and 6 also anticipating instant claims 18-19), and those claims that are not anticipated by the ‘868 claims are clearly obvious over the ‘868 claims (as those claims recite probes covalently linked to one or more of the same preferred types of detectable moieties).
Claims 5, 8, 10, 13-16, and 18-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 11,124,824 (cited in IDS). Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
As discussed above, independent claim 5 as amended has been interpreted as requiring a nucleic acid probe meeting the length and sequence/structure requirement specified in the claim and “a 3’ end and/or 5’ end that is covalently linked to at least one detectable label”, while independent claim 16 has been interpreted as being directed to a nucleic acid probe comprising SEQ ID NO: 2 covalently linked to a detectable label.
The ‘824 patent claims methods in which probes meeting the requirements of the present claims are either employed (such that the products of the instant claims are anticipated by the ‘824 claims), or clearly suggested by the products employed in the methods of the ‘824 claims. More particularly, probes meeting the requirements of claims 5, 8, 10, and 13-15, are recited in, e.g., ‘824 claims 1-2, 11-15, and 18 (with claim 15 specifying a biotin label as required by claim 8). With regard to claim 16 and claims dependent therefrom (claims 18-19), while the ‘824 claims do not recite a probe comprising SEQ ID NO: 2, the ‘824 claims do recite probes “complementary to at least 50 contiguous nucleotides of SEQ ID NO: 2” (see claim 2), which would have suggested to one of ordinary skill in the art Alu probes including SEQ ID NO: 2; such an artisan
would have readily recognized that either strand of such a (specifically recited, preferred) nucleic acid could be successfully employed as a probe. Further, labeling as specified in claims 18-19 is suggested by, e.g., ‘824 claims 1 and 12-15. Thus, the instant claims are not patentably distinct from the ‘824 claims.
Claims 6, 9, 17, and 20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 11,124,824 in view of Hoon et al.
As discussed above, instant claim 5 (from which claims 6 and 9 depend) and instant claim 16 (from which 17 and 20 depend) are not patentably distinct from the ‘824 claims. The ‘824 claims recite probes covalently linked to a detectable label at the 3’ or 5’ end, and do not encompass probes including multiple labels (as required by claims 6 and 17), or probes including a fluorescent molecule (as required by claims 9 and 20).
Hoon et al teach methods comprising detection of “free circulating” DNA (a.k.a. cell-free DNA) in body fluids, which methods – like those of the ‘824 claims - include targeting Alu sequences in the cfDNA (see entire reference, particularly the Summary at page 1-4). More particularly, Hoon et al disclose methods comprising obtaining any body fluid sample (including a urine sample; see, e.g., page 3 at line 19; page 11 at line 15), and detecting and quantitating the cfDNA therein, with a preferred method being qPCR employing fluorogenic probes detectably labeled with a fluorophore and quencher (see entire reference, particularly, e.g., pages 11-12).
In view of the teachings of Hoon et al, it would have been prima facie obvious to one of ordinary skill in the art as of the effective filing date of the claimed invention to have labeled probes as set forth in the ‘824 claims in the manner taught by Hoon et al, i.e., to have included multiple labels/moieties including “a fluorescent molecule”. An ordinary artisan would have been motivated to have made such a modification for the benefit of preparing alternative probes labeled for successful use in the preferred methods taught by Hoon et al. With further regard to claim 6 and 17, and particularly given that Hoon et al disclose that multiple moieties on a single probe are employed in some types of detection methods/assays, while the claims in view of Hoon et al do not explicitly suggest the use of “at least three detectable moieties”, an ordinary artisan would have considered the addition of further moieties as routine optimization, and would have been motivated to have included additional moieties as needed depending upon the manner in which a probe was to be used. Thus, claims 6, 9, 17, and 20 are not patentably distinct from the ‘824 claims in view of Hoon et al.
Claims 5-6, 8-10, and 13-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 11,505,822 (cited in IDS). Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
Regarding claims 5-6, 8-10, and 13-15, the ‘822 claims anticipate the instant claims. More particularly, the ‘822 claims recite mixtures including Alu sequence targeting probes (particularly targeting at least 70 consecutive nucleotides of ‘822 SEQ ID NO: 1, which is identical to instant SEQ ID NO: 1), which probes are 3’ and/or 5’ labeled with detectable moieties that may include biotin (see, e.g., claim 3) or a fluorescent molecule (see, e.g., claims 2 and 6); the ‘822 claims also encompass probes attached to multiple moieties (see claims 8-11). Thus, the instant claims are not patentably distinct from the ‘823 claims.
Applicant’s request of 06 May 2026 (Reply at page 10) that the nonstatutory double patenting rejections be held in abeyance is noted; however, the amended claims remain rejected for the reasons given above.
Conclusion
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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/DIANA B JOHANNSEN/Primary Examiner, Art Unit 1682
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