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 .
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-3, 13-16, and 18-20) in the reply filed on 11/7/2025 is acknowledged.
It is noted that claims 4-7, 10-17, and 24 have been newly canceled. Claims 51-61 have been added. Claims 1-3, 18-20, and 51-61 are pending and are examined on the merits herein.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 10/9/2024 and 11/20/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Objections
Claim 2 is objected to because of the following informalities: the word “residue” should be removed from line 3, and “the 5mC of the sample nucleotide” in line 2 should read “the 5mC residue of the sample nucleotide”. Appropriate correction is required.
Claim 3 is objected to because of the following informality: in line 2 “a thymine residue at a position of the 5mC of the” should read “a thymine reside at a position of the 5mC residue of the”. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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.
Claims 58-59 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.
Claim 58 depends on claim 52, and recites “the thiol compound” in line 2. This phrase lacks antecedent basis, as “a thiol compound” is not recited previously in the claim, nor in claims 1 or 52, from which this claim depends. The claim will be interpreted as though “the thiol compound comprises” was placed in the claim erroneously, and so will be read as though it states “wherein the radical initiator comprises a transition metal.” This interpretation is supported by the disclosures of radical initiators being used together with thiols in the instant specification (e.g. paras. 50-51 and 111-112).
Claim 59 is rejected due to its dependence on rejected claim 58.
Claim Interpretation
Claim 1 requires the use of “a 5-methylcytosine residue” to undergo reducing and deamination. Firstly, it is noted that claim 1 comprises the listed steps, and so the residue may undergo additional treatments, so long as those treatments do not interfere with the reducing and deamination reactions’ ability to act on “a 5-methylcytosine residue”. Additionally, the instant specification does not provide a specific definition for “a 5-methylcytosine residue”. Thus, the claim will be interpreted under the broadest reasonable interpretation of the term, and will include both modified and unmodified 5-methylcytosine residues.
Claim 3 states that the treated nucleotide sequence must contain a thymine residue at the location of the 5mC. However, the claim does not state when this thymine residue must be present on the treated nucleotide sequence (e.g. if it must be present during the creation of the initial treated nucleotide sequence, or if it may be added to the treated nucleotide sequence later or through further treatments/manipulations not explicitly stated in the claim). The treated nucleotide sequence is produced in step b) of claim 1, and so prior art will be considered to read on this limitation if said prior art teaches that thymine is present on an analogous treated nucleotide sequence at any point after its initial creation. Additionally, para. 9 of the instant specification notes that when DHU is created, “Subsequent amplification of the nucleotide sequence can convert DHU to thymine, enabling a C-to-T transition of 5mC.” Para. 40 also states that converting to a DHU residue then, “gives rise to a C to T change in any subsequent amplification and sequencing.” Figure 1 and para. 50 describe similar processes, where, “Figure 1 is a schematic showing the general methods for detecting 5mC, 5hmC and 5fC via a 5caC conversion and a DHU product. C-to-T transitions are induced at locations containing the 5caC modification…” Thus, prior art will specifically be considered to read on this limitation if the treated nucleotide sequence undergoes manipulations to turn DHU resides into T residues, as this is considered a C-T conversion of the initial sequence by the instant specification.
Claim 18 requires that the population of polynucleotides comprising the sample comprise genomic DNA. It is noted that this claim does not require that genomic DNA specifically be targeted by or the sample recited in the method of claim 1 – it simply requires that genomic DNA be present with the sample. Additionally, the instant specification does not recite a specific definition noting the form in which the genomic DNA must be provided. For example, para. 210 notes that genomic DNA used may be fragmented, while para. 208 states that whole genomic DNA can also be used. Therefore, any collection of a population of polynucleotides where the sequence(s) of at least one polynucleotide contain a genomic DNA sequence will be considered to meet the limitation of claim 18.
Similar to claim 18, claim 19 requires that the population of polynucleotide comprising the sample comprise RNA. The RNA does not have to be specifically targeted by or the sample recited in the method of claim 1 – the claim simply requires that the RNA be present with the sample. Additionally, the instant specification does not recite a specific definition noting the form in which the RNA must be provided. For example, para. 210 notes that RNA used may be fragmented, while para. 208 states that whole RNA can also be used. Therefore, any collection of a population of polynucleotides where the sequence(s) of at least one polynucleotide contain an RNA sequence will be considered to meet the limitation of claim 19.
Claim Rejections - 35 USC § 103
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.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claims 1-3, 18, 51, and 61 are rejected under 35 U.S.C. 103 as being unpatentable over Arensdorf et al. (WO 2019/160994 A1).
Arensdorf teaches reaction mixtures, kits, and methods associated with epigenetic analysis of DNA (Abstract). In the method described in paras. 19-25, a sample with 5-hydroxymethylcytosine residues and unmodified 5-methylcytosines is provided, and the 5-hydroxymethylcytosine residues are then removed. The remaining unmodified 5-methylcytosines are then oxidized (creating modified oxidized 5-methylcytosine residues), and these oxidized residues are then contacted with organic borane to effectively reduce and deaminate said residues. This creates dihydrouracil residues that are then amplified and sequenced to determine a 5-methylation pattern. This 5-methylation pattern would identify the 5-methylcytosines in the sample sequences, and would therefore read on step (d) of instant claim 1. Thus, even though the methods of Arensdorf teach steps in addition to those provided by the instant claim, the instant claim is stated to only comprise the listed steps, and may therefore also include additional steps. See MPEP 2111.03 I. Additionally, it is noted that this rejection utilizes the interpretations provided by the “Claim Interpretation” section above, where the 5-methylcytosines may be modified 5-methylcytosines (in this case, the modified 5-methylcytosines are oxidized).
Thus, claim 1 is prima facie obvious over Arensdorf.
Regarding claims 2 and 51, Arensdorf teaches an example of their method in para. 106, starting with an oxidized 5-methylcytosine (5-carboxymethylcytosine). Figure 4 shows the exact chemical changes that occur during reduction and deamination of this molecule, and during reduction, the bond between the C5-C6 carbons is specifically reduced. During deamination, the C4 carbon specifically is shown to lose its -NH2 amino group. As 5-carboxymethylcytosine is one of the oxidized 5-methylcytosines specifically stated to be used in the method of paras. 19-25 described above in the rejection of instant claim 1, this embodiment thus encompasses the reduction described in instant claim 2 and the deamination described in instant claim 51.
Regarding claim 3, generally, the methods of Arensdorf take an oxidated 5-methylcytosine residue and convert it to a dihydrouracil residue (DHU; Abstract and para. 125, for example, see also Figures 4 and 5). However, in the specific sequencing methods developed by Arensdorf that are shown to work with 5-methylcytosine (TAPS and TAPS with βGT, see Table 1), after oxidation, reduction, and deamination of the 5-methylcytosine, the residue (along with its associated sequence) undergoes PCR, where the DHU is read as T (Figure 8). Additionally, Figure 11 refers to a single-tube method involving nucleotide treatment and conversion, where DHU is read as T (para. 129). In accordance with the “Claim Interpretation” section above, these teachings read on those of instant claim 3. As the embodiment of Arensdorf described above in the rejection of claim 1 involves the creation of DHU and further amplification and sequencing (see paras. 23-24), this embodiment thus also reads on instant claim 3.
Regarding claim 18, Arensdorf teaches in para. 60 that nucleic acid samples of their invention may include DNA targets that encompass genomic DNA. In the embodiment described above in the rejection of claim 1, cell-free DNA is used. As cell-free DNA contains fragmented genomic DNA sequences, this embodiment would encompass the limitations of instant claim 18 in accordance with the interpretation established in the “Claim Interpretation” section above.
Regarding claim 61, Arensdorf teaches methods of next-generation sequencing (para.76). Though the reference does not specify that the sequencing performed in the embodiment described above in paras. 19-25 in the rejection of claim 1 must be next-generation sequencing, Arensdorf notes that next-generation sequencing methods are high-throughput, allow for parallelized analysis of multiple sequences, and are commercially available (para. 76). Thus, when choosing a method to complete the sequencing required by the overall method described by Arensdorf above, the ordinary artisan would be motivated to choose a next-generation sequencing method due to the benefits of such methods as described by Arensdorf, and would have a reasonable expectation of success in doing so due to the commercial availability of such methods.
Claims 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Arensdorf et al. (WO 2019/160994 A1) in view of Savelyeva et al. (BioMed Research International, 2017).
Regarding claim 19, though the method of paras. 19-25 of Arensdorf recited above in the rejection of claim 1 utilizes cell-free DNA, para. 87 of Arensdorf states that cell-free DNA can be obtained by centrifuging whole blood to remove all cells, and then isolating the DNA from the remaining plasma. Additionally, the reference states that cell-free DNA refers to DNA in the peripheral blood of a patient (para. 87).
However, the reference does not specifically state that the sample used to obtain the cell-free DNA contains RNA.
Savelyeva teaches that human peripheral blood contains RNA in both cells and as cell-free molecules (Abstract and page 1, column 1, para. 1). The reference states that blood plasma in particular contains mRNAs and non-coding RNAs (page 2, column 1, para. 1), and that the cell-free ribonucleoproteins in blood plasma can contain ribosomal RNAs and transfer RNAs (page 2, column 1, para. 3).
Though it is not clear that a whole blood sample is used to isolate the cell-free DNA used in the teachings of Arensdorf described above in the rejection of claim 1, it would be prima facie obvious to the ordinary artisan prior to the effective filing date of the claimed invention that such a sample could be used. Arensdorf teaches that cell-free DNA can be extracted from whole blood samples from patients with diseases, and particularly can derive from tumors (para. 119). Thus, the ordinary artisan would be motivated to use whole blood samples from patients for use in the method of Arensdorf, as any analysis of said samples may provide information about a disease state or tumor progression, which can affect patients’ prognoses and treatment plans. These whole blood samples are also relatively easy to obtain non-invasively from a patient, furthering their usefulness and providing a reasonable expectation of success in obtaining them. As Savelyeva teaches, whole blood samples have mRNAs, rRNAs, tRNAs, and non-coding RNAs, and so by utilizing whole blood samples, the limitations of instant claims 19 and 20 would be met.
Thus, claims 19 and 20 are prima facie obvious over Arensdorf in view of Savelyeva.
Claims 52 and 58 are rejected under 35 U.S.C. 103 as being unpatentable over Arensdorf et al. (WO 2019/160994 A1), as evidenced by Okamoto et al. (US 2018/0251815 A1).
Arensdorf teaches the method of claim 1, as described above. In para. 102, the reference teaches that oxidation of 5mC may occur via the use of a combination of peroxotungstate and a copper (II) perchlorate/2,2,6,6-tetramethylpiperidine-l-oxyl (TEMPO) combination.
Okamoto teaches oxidizing agents for 5-hydromethylcytosine that include the use of radical molecules (Abstract). The reference specifically notes that TEMPO is considered a nitroxyl radical molecule (para. 58).
In the embodiment of paras. 19-25 of Arensdorf described above in the rejection of claim 1, the specific means for oxidizing are not described, and so it would be prima facie obvious for the ordinary artisan to use an oxidizing method described by Arensdorf in the method of Arensdorf, as such methods have already been demonstrated to work within the general invention of Arensdorf (and would be encompassed by the general oxidizing described in paras. 19-25). The use of peroxotungstate and TEMPO in particular is noted to work with cell-free DNA samples, which are also recited in the embodiment of paras. 19-25, furthering providing a reasonable expectation of success.
Thus, claims 52 and 58 are prima facie obvious over Arensdorf as evidenced by Okamoto.
Claims 53-57 are rejected under 35 U.S.C. 103 as being unpatentable over Arensdorf et al. (WO 2019/160994 A1), as evidenced by Okamoto et al. (US 2018/0251815 A1), and in view of Liutkevičiūtė et al. (Angew. Chem. Int. Ed., 2011).
Regarding claims 53 and 55-57, Arensdorf as evidenced by Okamoto teaches the method of claim 52, as described above. However, the reference does not teach the specific addition of thiol compounds. It is noted that the reference does mention that S atoms may be added to nitrogen heterocycles, but this is not the same as a thiol group (para. 103).
Liutkevičiūtė examines the behavior of 5hmC residues within DNA sequences (page 2090, column 2, para. 2). The reference teaches that when 2-mercaptoethanol is added to 5hmC, a new product is produced at the expense of 5hmc (page 2090, column 2, para. 2 and Figure 1).
Prior to the effective filing date of the claimed invention, it would have been prima facie obvious for one of ordinary skill in the art to add 2-mercaptoethanol as taught in Liutkevičiūtė to the embodiment of Arensdorf as evidenced by Okamoto described above in the rejection of claim 52 in order to transform any remaining 5hmCs left in solution, so that 5mCs may be solely focused on. In the embodiment of paras. 19-25 of Arensdorf described above, 5hmCs are removed before 5mCs are oxidized. However, 5hmC can be affected by TEMPO, as shown in Okamoto, and so any 5hmC erroneously left in a reaction mixture may interfere with results if one only wishes to analyze 5mC. Thus, if 2-mercaptoethanol is added during treatment of 5mC, it would ensure that any erroneous 5hmC (left due to incomplete tagging or removal) would likely be transformed, and therefore, even if the transformed product is affected by later reaction components, it would not result in the production of DHU. As Liutkevičiūtė teaches that 2-mercaptoethanol can easily be added to solution, there would be a reasonable expectation of success.
It is noted that 2-mercaptoethanol has the formula HSCH2CH2OH, and so contains a thiol group attached to an alkyl group, as well as a hydroxyl group.
Thus, claims 53 and 55-57 are prima facie obvious over Arensdorf, as evidenced by Okamoto, and in view of Liutkevičiūtė.
Regarding claim 54, Liutkevičiūtė also teaches the addition of dithiothreitol to 5hmC (Figure 1b). This produced a similar effect to the use of 2-mercaptoethanol, where less 5hmC was found compared to controls. In the case of dithiothreitol, it also appears that no additional modified C nucleotides were produced, which is also similar to the effect of 2-mercaptoethanol.
Thus, prior to the effective filing date of the claimed invention, it would have been prima facie obvious for one of ordinary skill in the art to add dithiothreitol as taught in Liutkevičiūtė to the embodiment of Arensdorf as evidenced by Okamoto described above in the rejection of claim 52 in order to transform any remaining 5hmCs left in solution, so that 5mCs may be solely focused on. In the embodiment of paras. 19-25 of Arensdorf described above, 5hmCs are removed before 5mCs are oxidized. However, 5hmC can be affected by TEMPO, as shown in Okamoto, and so any 5hmC erroneously left in a reaction mixture may interfere with results if one only wishes to analyze 5mC. Thus, if dithiothreitol is added during treatment of 5mC, it would ensure that any erroneous 5hmC (left due to incomplete tagging or removal) would likely be transformed, and therefore, even if the transformed product is affected by later reaction components, it would not result in the production of DHU. As Liutkevičiūtė teaches that dithiothreitol can be added to solution, there would be a reasonable expectation of success.
Thus, claim 54 is prima facie obvious over Arensdorf, as evidenced by Okamoto, and in view of Liutkevičiūtė.
Claim 59 is rejected under 35 U.S.C. 103 as being unpatentable over Arensdorf et al. (WO 2019/160994 A1), as evidenced by Okamoto et al. (US 2018/0251815 A1), and in view of Zhang (WO 2019/067699 A1).
Arensdorf as evidenced by Okamoto teaches the method of claim 58, as described above. Arensdorf also generally teaches that oxidation of the 5mC residues may generally be carried out using a chemical oxidizing agent, with no particular limit on the type of agent (para. 123).
Zhang teaches methods for measuring compounds and diagnosing and monitoring disease (Abstract). To prepare certain compounds, Zhang teaches that radical initiators may be used with iridium complexes (page 33, para. 5 and page 49, para. 2).
Prior to the effective filing date of the claimed invention, it would have been prima facie obvious for one of ordinary skill in the art to substitute the transition metal compound described by Arensdorf as evidenced by Okamoto with that of Zhang. MPEP 2143 I (B) states, “The rationale to support a conclusion that the claim would have been obvious is that the substitution of one known element for another yields predictable results to one of ordinary skill in the art.” Zhang teaches that iridium complexes may be used with radical initiators, particularly to catalyze reactions (page 33, para. 5 and page 49, para. 2). Thus, using an iridium complex with the radical initiator described above in Arensdorf as evidenced by Okamoto would still be capable of catalyzing reactions, and so could be used for the oxidation reaction described by Arensdorf. As the product generated by the oxidation of 5mC is predictable (see Figure 8 of Arensdorf for example), the results of this substitution would also be predictable.
Thus, claim 59 is prima facie obvious over Arensdorf, as evidenced by Okamoto, and in view of Zhang.
Claim 60 is rejected under 35 U.S.C. 103 as being unpatentable over Arensdorf et al. (WO 2019/160994 A1) in view of Yu et al. (Cell, 2012).
Regarding claim 60, Arensdorf teaches the method of claim 1, as described above. The reference also teaches that the molecules of their invention may be modified with bisulfite (para. 152), and generally teaches the use of bisulfite sequencing (see Table 1 for example). However, the reference does not teach using bisulfite in the embodiment described above in the rejection of claim 1.
Yu teaches the use of TET-assisted bisulfite sequencing (TAB-Seq), which when combined with traditional bisulfite sequencing is capable of distinguishing 5-hydroxylmethylcytosine from 5-methylcytosine (Abstract). The basic methodology for TAB-Seq is laid out in Figure 1A – where 5mC and 5hmC exist together in a sample, the 5hmC resides can be protected by glucosylation,. Then, the sequence can undergo oxidation with TET and bisulfite treatment, and the resulting 5hmC resides appear as C, while the 5mC appear as T. Yu teaches that this method provides single-base resolution and can, “examine previously reported 5hmC-enriched loci and successfully identified genuine 5hmC sites,” (page 1377, column 1, para. 1 to column 2, para. 1).
Arensdorf admits the problems associated with distinguishing between 5mC and 5hmC in bisulfite sequencing (para. 5). The reference also states that TET can be used to oxidize the 5-methylcytosine of paras. 19-25 (see para. 30, and also paras. 102 and 123 and Figure 11 for other examples). In Table 1, Arensdorf shows sequencing methods that can distinguish between 5mC and 5hmC, including oxidative bisulfite sequencing, and methods for sequencing involving the blocking of 5hmC residues, such as TAPS with βGT (para. 126). Thus, the method described by Yu is an alternative way of accomplishing this distinction between 5mC and 5hmC that allows for both residues to simultaneously exist within a sequence (eliminating the need for the removal of 5hmC, as is done in the embodiment described in paras. 19-25 of Arensdorf), while combining elements from the different sequencing techniques of Arensdorf (e.g. the use of bisulfite and TET). By not needing to remove 5mhC from the sample mixture before manipulating the sequences/residues, this overall simplifies the method and makes it less prone to error/noise, as an errant 5hmC in the reaction mixture will not affect the analysis of results, as 5hmCs are specifically dealt with in such sequencing. The use of the sequencing of Yu, which involves specific bisulfite treatment after the use of TET, can be considered a substitution of the sequencing methods described by Arensdorf with those of Yu. MPEP 2143 I (B) states, “The rationale to support a conclusion that the claim would have been obvious is that the substitution of one known element for another yields predictable results to one of ordinary skill in the art.” The results of using TAB-Seq with a sequence containing 5hmC and 5mC would be predictable, as said results are described by Yu. These results are also similar to the results described by paras. 125-126 and Table 1 of Arensdorf, providing a reasonable expectation of success and confidence that the method would work as intended.
Thus, claim 60 is prima facie obvious over Arensdorf in view of Yu.
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 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 15 of copending Application No. 18/534,106 (reference application) in view of Arensdorf et al. (WO 2019/160994 A1).
Although the claims at issue are not identical, they are not patentably distinct from each other. Claim 15 of the ‘106 application depends on claim 1, and recites that step (iii) may include reduction and deamination processes. In claim 1, a 5-methylcytosine may be examined, where the 5-methylcytosine is within a sample within a larger population of polynucleotides, as in instant claim 1. Claim 1 (and thus, claim 15) of the ‘106 application also involves an oxidation reaction, but as noted above in the “Claim Interpretation” section, such an additional reaction is not prohibited by the instant claims, as it results in a modified oxidized 5-methylcytosine residue. Step (iv) of claim 1 (and thus, claim 15) of the ‘106 application also involves identifying the treated results within the population. Thus, claim 15 of the ‘106 application encompasses all the steps of instant claim 1, with the exception of the sequencing recited in step c) of instant claim 1. However, it would be obvious that sequencing could be used in the identification step of (iv) of claims 1 and 15 of the ‘106 application, particularly as such sequencing is recited in claim 16 of the ‘106 application. Additionally, Arensdorf teaches a method similar to that of claim 15 of the ‘106 application, where a 5’-methylcytosine may be oxidized, reduced, and deaminated (e.g. paras. 9 and 19-25). Arensdorf explicitly teaches sequencing methods in order to identify the treated residues (para. 24). Arensdorf teaches that this sequencing can detect methylation patterns (para. 25), and would therefore be a clear way to distinguish treated 5-methylcytosine residues from unmethylated residues in a sequence. Arensdorf also teaches that high-throughput, next-generation sequencing methods are well-known in the art and are commercially available (para. 76), providing additional motivation and a reasonable expectation of success at utilizing such methods.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are currently allowable.
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/FRANCESCA FILIPPA GIAMMONA/Examiner, Art Unit 1681