DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Status of Application, Amendments, And/Or Claims
The Applicants amendments/remarks received 4/30/2026 are acknowledged. Claims 1, 8-10, 22-23 and 31 are amended; claims 11-20 are canceled; no claims are withdrawn; claims 1-10 and 21-31 are pending and have been examined on the merits.
Information Disclosure Statement
The information disclosure statement submitted on 4/30/2026 has been considered by the examiner.
Claim Rejections - 35 USC § 112
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 1-10 and 21-31 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 inventors, at the time the application was filed, had possession of the claimed invention.
The original disclosure does not disclose a method for detecting a methylated cytosine residue in mammalian nucleic acid, comprising contacting said mammalian nucleic acid molecule comprising said methylated cytosine residue with a TET family protein or catalytically active fragment thereof to generate a product nucleic acid comprising a modified methylated cytosine residue; derivatizing said modified methylated cytosine residue in said product nucleic acid with a glucose molecule or a glucose-derivative donor substrate; amplifying said product nucleic acid to generate an amplified product nucleic acid: and performing a sequencing reaction on said amplified product nucleic acid or a derivative thereof, to identify a presence of said methylated cytosine residue in said mammalian nucleic acid; hence, claims 1-10 and 21-31 constitute new matter and are rejected under 35 U.S.C. 112(a) for failing to comply with the written description requirement by constituting new matter.
Response to Arguments
Applicant's arguments filed 4/30/2026 have been fully considered but they are not persuasive. The argument of the Applicant’s Response on p. 8 regarding the rejection on the ground of nonstatutory double patenting is moot as the rejection has been withdrawn in view of the filing and approval of a terminal disclaimer over 12331346 on 4/30/2026.
Regarding the rejection of claims 1-10 and 21-31 under 35 U.S.C. 112(a) for constituting new matter, Applicant fails to demonstrate the disclosure of the claimed method in the instant disclosure or any priority document; thus, the rejection is maintained.
Applicant argues that the method of claim 1 is disclosed in provisional application 61/121844 (herein “’844”) and PCT application PCT/US09/58562 (herein “’562”) (Remarks, pp. 5-7). Applicant argues that ‘844 and/or ‘562 recite certain claim terms or steps or substeps (pp. 5-7); however, Applicant does not persuasively show that the instant disclosure or priority documents disclose a method comprising a) contacting a mammalian nucleic acid molecule comprising a methylated cytosine residue with a TET family protein or catalytically active fragment thereof to generate a product nucleic acid comprising a modified methylated cytosine residue, b) derivatizing said modified methylated cytosine residue in said product nucleic acid with a glucose molecule or a glucose-derivative donor substrate, c) amplifying said product nucleic acid to generate an amplified product nucleic acid, and d) performing a sequencing reaction on said amplified product nucleic acid or a derivative thereof, to identify a presence of said methylated cytosine residue in said mammalian nucleic acid.
Regarding step c), Applicant points to [000166] of ‘844 (p. 6) wherein polymerase chain reaction (PCR) is used to clone the coding sequence of protein for expression of the recombinant protein. This has absolutely nothing to do with the method of claim 1. The amplification is NOT an amplification of a mammalian nucleic acid molecule comprising a methylated cytosine residue which has been contacted with a TET family protein to convert methylated cytosine to a modified methylated cytosine residue followed by derivatization of the modified methylated cytosine residue with a glucose molecule. Rather, it is the unrelated process of cloning a cDNA for recombinant protein expression. If this is the best support for step c) in ‘844, then ‘844 clearly does not disclose the method of claim 1 and claims 1-10 and 21-31 clearly constitute new matter.
Applicant further points to [0155] and [0356] of ‘562 to allegedly provide support for step c) (p. 6). [0155] is drawn to sequencing or amplifying genomic regions comprising 5-hydroxymethylcytosine residues and [0356] is drawn to amplifying minigenes with a PCR mix comprising methylated or hydroxymethylated deoxycytidine residues followed by checking the PCR products on an agarose gel. Neither [0155] and [0356] of ‘562 disclose amplifying a mammalian nucleic acid molecule wherein methylated cytosine residues have been oxidized by a TET family member to modified methylated cytosine residues then the modified methylated cytosine residues were derivatized with a glucose derivative. Nor is [0155] and [0356] of ‘562 drawn to identifying a methylated cytosine residue in said mammalian nucleic acid. If this is the best support for step c) in ‘562, then ‘562 clearly does not disclose the method of claim 1 and claims 1-10 and 21-31 clearly constitute new matter.
Regarding step d), Applicant argues that [000103] of ‘844 discloses the sequencing step (pp. 6-7). [000103] of ‘844 discloses the bisulfite sequencing of genomic DNA wherein the genomic DNA is contacted with sodium hydrogen sulfate (bisulfite) which sulfonates unmethylated cytosine; the sulfonated unmethylated cytosine spontaneously deaminates to form sulfonated uracil; the pH of the composition is lowered to desulfonate the uracil; then the bisulfite-treated, acid-treated genomic DNA is amplified or sequenced. The instant method does not treat the nucleic acid with bisulfite nor acid and there is no disclosure of the conversion of unmethylated cytosine to uracil in the instant method. [000103] of ‘844 does not disclose that the genomic DNA has been treated with a TET family member to convert methylated cytosines to modified methylated cytosines; does not disclose that the modified methylated cytosines have been derivatized with a glucose derivative, nor discloses identifying methylated cytosines in TET-treated, glucose-derivatized nucleic acid. If this is the best support for step d) in ‘844, then ‘844 clearly does not disclose the method of claim 1 and claims 1-10 and 21-31 clearly constitute new matter.
In conclusion, claims 1-10 and 21-31 clearly constitute new matter which is not disclosed in the instant disclosure or any priority document; hence, the rejection of claims 1-10 and 21-31 under 35 U.S.C. 112(a) for failing to comply with the written description requirement by constituting new matter is maintained.
Claim Rejections - 35 USC § 112
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 1-10 and 21-31 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 1 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. The omitted steps are: detecting a methylated cytosine residue. Claim 1, thus, also dependent claims 2-9 and 21-31, is drawn to a method for detecting a methylated cytosine residue in mammalian nucleic acid; however, it is completely unclear how methylated cytosine residues are detected in the claimed method. The claim recites modifying methylated cytosine residues with at least a catalytically active fragment of a TET family member; derivatizing the modified methylated cytosine residue with glucose or analog; amplifying the derivatized nucleic acid and sequencing the amplified product; however, the claim does not in any way describe how the method steps lead to the detection of a methylated cytosine residue in the nucleic acid. Therefore, claims 1-10 and 21-31 are rejected under 35 U.S.C. 112(b) as being indefinite.
Response to Arguments
Regarding the rejection of claims 1-10 and 21-31 for indefiniteness because it is unclear how the method identifies methylated cytosine residues, Applicant argues that the claim is no longer indefinite because “A method for detecting a methylated cytosine residue in mammalian nucleic acid, comprising” has been amended to “A method comprising”. This is unpersuasive because removing the preamble does not disclose how the claimed method actually identifies methylated cytosine residues. Neither the instant disclosure nor instant claims in any way describe how the method steps lead to the detection of a methylated cytosine residue in the nucleic acid; hence, the rejection of claims 1-10 and 21-31 under 35 U.S.C. 112(b) as being indefinite is maintained.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-7, 10, 21, 23, 25 and 30-31 are rejected under 35 U.S.C. 102(a)(1)/102(a)(2) as being anticipated by Banila et al., US 2024/0336951 (cite A, attached PTO-892).
Banila teaches a method (Examples 3-4, [0230-278]) for detecting methylated cytosine residues in mammalian nucleic acid, comprising isolating mammalian genomic DNA from human epidermal samples [0230-240], contacting said mammalian DNA comprising said methylated cytosine residue with a TET family protein or catalytically active fragment thereof to generate a product DNA [0241-244], derivatizing said modified methylated cytosine residue in said product DNA with a UDP-glucose by contacting said product DNA with a β-glucosyltransferase (BGT) [0244]; contacting the product DNA with a deaminase; amplifying said product nucleic acid by polymerase chain reaction (PCR) to generate an amplified product nucleic acid [0244]; and performing a sequencing reaction on said amplified product nucleic acid or a derivative thereof [0244]; wherein unmodified cytosine (C) residues are deaminated to uracil (U) which is converted to thymidine (T) during PCR amplification, while oxidized cytosine residues (5-formyl cytosine and 5-carboxyl cytosine) and glycosylated cytosine residues (derivatized from 5hmC residues by BGT) are converted to C during PCR amplification; hence, in the sequencing reaction unmethylated C is identified as T and methylated C is identified as C; thus, the methylated cytosine residues can be identified by comparison with reference sequences of the DNA sequence; anticipating claims 1, 10, 21, 23, 25 and 30-31.
Banila discloses that the TET enzyme can be TET1, TET2, TET3 or a functional derivative thereof [0005] anticipating claims 2-7.
Response to Arguments
Regarding the rejection of claims 1-7, 10, 21, 23, 25, 30, and 31 under pre-AIA 35 U.S.C. § 102(a) over Banila and the rejection of claims 1-10, 21, 23, 25, 30, and 31 under 35 U.S.C. § 103 over Banila (Remarks, pp. 7-8), Applicant argues that Banila is not prior art. This is incorrect as the instant claims are not disclosed in the instant disclosure nor any priority document. Hence, the effective filing date is the filing date of the instant claims. Applicant correctly points out that the rejection should not be pre-AIA if the effective filing date is the filing date of the instant application, 8/4/2025 (p. 7); hence, the rejection is now under 35 U.S.C. 102(a)(1)/102(a)(2). As stated on p. 8 above, 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 pre-AIA to 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.
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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) 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 under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 1-10, 21, 23, 25 and 30-31 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Banila.
The discussion of Banila regarding claims 1-7, 10, 21, 23, 25 and 30-31 set forth in the rejection above is incorporated herein.
Banila discloses that the sequencing can be whole genome sequencing [0007] or array hybridization [0172]; hence, a person of ordinary skill in the art at the time of filing would have found it obvious for the method to comprise whole genome sequencing or array hybridization; therefore, claims 8 and 9 are prima facie obvious.
Response to Arguments
Regarding the rejection of claims 1-7, 10, 21, 23, 25, 30, and 31 under pre-AIA 35 U.S.C. § 102(a) over Banila and the rejection of claims 1-10, 21, 23, 25, 30, and 31 under 35 U.S.C. § 103 over Banila (Remarks, pp. 7-8), Applicant argues that Banila is not prior art. This is incorrect as the instant claims are not disclosed in the instant disclosure nor any priority document.
Double Patenting
The rejection of claims 1-10 and 21-31 on the ground of nonstatutory double patenting over claims 1 and 11-26 of U.S. Patent No. 12331346 as set forth at pp. 9-13 of the previous Office Action, is withdrawn in view of the filing and approval of a terminal disclaimer over 12331346 on 4/30/2026.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Trent R Clarke whose telephone number is (571)272-2904. The examiner can normally be reached M-F 10-7 MST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melenie Gordon can be reached at 571-272-8037. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TRENT R CLARKE/ Examiner, Art Unit 1651
/DAVID W BERKE-SCHLESSEL/ Primary Examiner, Art Unit 1651
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