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 .
Claim Status
Currently, claims 1-3, 5-30 are pending in the instant application. Claim 4 has been canceled and claims 10-25 and 30 is withdrawn. This action is written in response to applicant' s correspondence submitted 02/23/2026. All the amendments and arguments have been thoroughly reviewed but were found insufficient to place the instantly examined claims in condition for allowance. The following rejections are either newly presented, as necessitated by amendment, or are reiterated from the previous office action. Any rejections not reiterated in this action have been withdrawn as necessitated by applicant' s amendments to the claims. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action. This action is FINAL.
Claims 1-3, 5-9, 26-29 are under examination. The elected species of SEQ ID NO 15 and SEQ ID NO 16 is free of the art. Search and examination has been extended to the next species, SEQ ID NO 1 and SEQ ID NO 2.
Withdrawn Rejections
The rejection of claims 1-4, 5-6, 28, and 29 under 35 USC 101 is withdrawn in view of the amendment to the claims.
The rejection of claims 1,4, 7-9, 26-29 under 35 U.S.C. 102(a)(1) as being anticipated by Jongruja (2010, cited on IDS) is withdrawn in view of the amendment to the claims.
The rejection of claims 1-4, 7-8, 26, and 28-29 under 35 U.S.C. 102(a)(1) as being anticipated by Nowotny (2008, cited on IDS) is withdrawn in view of the amendment to the claims.
The rejection of claims 1-2, 4, 7-8, 26, and 28-29 under 35 U.S.C. 102(a)(1) as being anticipated by Stopar (2019, cited on IDS) is withdrawn in view of the amendment to the claims.
The rejection of claim 5-6 are rejected under 35 U.S.C. 103 as being unpatentable over Stopar (2019, cited on IDS) in view of Meldal (F1000 Research 2016, 5, pp. 1-11) is withdrawn in view of the amendment to the claims.
Maintained Rejections
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 7 is rejected under 35 U.S.C. 101 because the claimed invention is directed to law of nature without significantly more.
The claims are directed to a law of nature. The claims are drawn to a composition of matter and encompass a natural phenomenon. Specifically the claims are drawn to a composition that comprises a naturally occurring nucleic acid sequence. Claim 7-9 and 26-27 are naturally occurring nucleic acid sequences. Claim 7 encompass a composition comprising a nucleic acid sequence encoding an epiprinter or a fragment thereof, which encompasses fragments that are naturally occurring. SEQ ID NO 16 is identical to a portion of the Rnase H1 sequence from Thermotoga maritima. Because the claims encompass a composition comprising known naturally occurring amino acids and nucleic acids of Rnase H1 from Thermotoga maritima, the claims encompass a law of nature. Such isolated nucleic acid molecules and protein sequences that are identical to fragments of naturally occurring nucleic acid are naturally occurring sequences.
There is no indication in the specification that the HBDs and nucleic acids encoding HBDs claimed here have any structural or functional characteristics that differ from the naturally occurring nucleic acids or proteins. Additionally the claims reciting a composition comprising an epitape molecule does not result in a structure that is markedly different than the naturally occurring nucleic acid sequence or amino acid sequence because the composition and epitape conveys the same nucleic acid sequence and amino acid sequence.
There is no indication that the composition, isolated nucleic acid or HBD binding domain results in changing the structure, function or other properties of the naturally occurring protein or nucleic acid. According the enzymes and nucleic acids are a product of nature exception and the claim is directed to at least one exception. This judicial exception is not integrated into a practical application because the claims recite a composition or a fragment of an epitape molecules that are naturally occurring and the epitape molecules encompass naturally occurring sequences. Many cited prior art references in this record demonstrate HBD domain, and nucleic acid encoding HBD domains are naturally occurring sequences.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims as a whole are not considered to recite any additional elements that amount to significantly more than the naturally occurring nucleotide sequences and protein sequences. Besides the nucleic acids and protein sequence, the claims recite a composition in the preamble and epitape molecule with a reactive moiety. The recitation of reactive moiety encompasses naturally occurring amino acids. At the time the invention was made compositions comprising nucleic acid sequences and protein sequences was well-established, routine and conventional. Additionally where a composition is recited at such a high level of generality it does not meaningfully limit the claim. The recitation of composition or epitape do not structurally change the nucleic acid sequence or protein sequence and is not significantly more than the naturally occurring sequence. Thus the claims as a whole does not amount to significantly more than each “product of nature” by itself and the claims do not qualify as eligible subject matter.
Accordingly, it is determined that the instant claims are not directed to patent eligible subject matter.
Response to Arguments
The response traverses the rejection on page 11-13 of the remarks mailed 02/23/2026. The response asserts that amino acids of SEQ I DNO 2, 8, 14, 16, and 19 and nucleotide sequences comprising at least 168 consecutive nucleotides of SEQ ID NO 1, 5, 6, 7, 9, 10, 11, 12, 13, 15, 17 and 18 are not naturally occurring sequences. This response has been reviewed but not found persuasive. The claim is not limited to the sequences of SEQ ID NO 1, 5, 6, 7, 9, 10-13, 15, and 17-18 or at least 168 consecutive nucleotides. The claims recite a composition comprising a nucleotide sequence encoding the epiprinter molecule of claim 1 or a fragment thereof. The recitation of fragment thereof does not limit the length of the nucleotide sequence and the nucleic acid sequence of HBD is naturally occurring. Therefore the claims are directed to naturally occurring sequences and are not patent eligible subject matter.
New Grounds of Rejection
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 5-6 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 5 recites the reactive moiety is an alkyl azide group and claim 6 recites a side group of an amino-acid residue included in a linker sequence between two HBDs. The recitation of an alkyl azide group and included in a linker sequence between two HBDs renders the claims indefinite. Claim 5 and 6 depend from claim 1. Claim 1 recites at least one reactive moiety and requires amino acid sequence of SEQ ID NO 2 and 16, consistent with the elected invention. However SEQ ID NO 2 does not comprise a linker sequence or 2 HBDs and therefore it is unclear what the reactive moiety of SEQ ID NO 2 comprises, does this limitation require additional sequence or moiety beyond what is encompassed by SEQ ID NO 2, is the reactive moiety a separate component of the composition. Additionally it is unclear what the reactive moiety is within SEQ ID NO 16 as SEQ ID NO 16 does not encompass a reactive moiety only amino acid residues. While amino acid resides can be considered a reactive moiety it is unclear which amino acid would be considered the reactive moiety and which amino acid would comprise an alkyl azide group. The metes and bounds of the claims are indefinite and one of ordinary skill in the art would not be reasonably apprised of infringing on the claimed invention.
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.
Claims 7 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Nelson (Nature 1999, Vol 399, pp 323-329).
Nelson teaches the Thermotoga maritima MS8 genomic sequence. This sequence comprises a fragment of SEQ ID NO 1 and SEQ ID NO 16, which is a fragment of a sequence that encodes an amino acid sequence of SEQ ID NO 2 and SEQ ID NO 15 (see alignment)
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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.
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.
Claim 1, 7-9, 26-29 are rejected under 35 U.S.C. 103 as being unpatentable over Jongruja (2010, cited on IDS) in view of Nowotny (cited on IDS).
Jongruja teaches the amino acid sequence of Tma-Rnase H1 (see figure 1). The amino acid sequence of Tma-Rnase H1 from 1-63 is identical to SEQ ID NO 2 from position 21 to 75. Jongruja does not teach an amino acid sequence that comprises position 1-20 of SEQ ID NO 2. Jongruja teaches the genomic sequence of Tma-Rnase H1, MSB8 (see plasmid construction) and teaches the Tma Rnase H1, Tema-CN and Tma-ND was constructed using pET25B. Jongruja does not teach the use of a plasmid that comprises a histidine tag and a thrombin cleavage site for constructing the Tma-Rnase H1.
However it was well known in the art to use plasmid construction that includes a histidine tag and thrombin cleavage site for ease of cloning and producing a protein. Nowotny teaches DNA constructs and protein purification of Rnase H. Nowotny teaches the Rnase H was cloned into pET15b which contains a N terminal his tag followed by a thrombin cleavage site (see experimental procedures, pg. 1014)
Therefore it would have been prima obvious to one of ordinary skill in the art at the time the invention was made to clone the HBD domain of Tma-Rnase H1 as taught by Jongruja by inserting the sequence into a pet15B vector as taught by Nowton. The DNA construct and resulting protein, as described by Nowton would comprise the HBD domain of Tmase-Rnase H1 with a thrombin cleavage site and his tag sequence which renders obvious SEQ ID NO 2. Additionally the DNA construct would render obvious SEQ ID NO 1. The ordinary artisan would have been a motivated to use the pet15B plasmid as taught by Notowny with the Tma-Rnase H1 sequence as taught by Jongruja with reasonable expectation of success because Notowny teaches plasmid construct and protein purification of RNase H and Jongruja teaches plasmid construct and protein purification of Tma-Rnase H1 and the ordinary artisan would have had motivation to include his tag and thrombin cleavage site to allow for ease of purification of the Rnase H1.
Claims 2-3 are rejected under 35 U.S.C. 103 as being unpatentable over Jongruja (2010, cited on IDS) in view of Notowny as applied to claim 1 above, and further in view of Stopar (2019, cited on IDS).
Jongruja in view of Notowny render obvious an amino acid sequence comprising SEQ ID NO 2. Jongruja in view of Notowny does not teach a composition comprising two or three HBDs.
However Stopar teaches a multimeric form of a cloned sequence of HBD from Rnase H1 that contains two copies of HBD connected by a 10 residue linker. Stopar teaches the dimeric form has a higher affinity than a monomeric HBD for a 20bp hybrid.
Therefore it would have been prima facie obvious to one of ordinary skill in the art to modify the HBD domain taught by Jongruja in view of Nowotony and include two or three HBD domains as taught by Stopar to allow for a composition that has higher affinity for a RNA-DNA heteroduplexes. The ordinary artisan would have been motivated with a reasonable expectation of success to modify the HBD taught by Jongrujg in view of Notowny with addition HDBs in a composition as taught by Stopar because Stopar teaches linking Tma-Rnase H1 HDB with two HBDs to allow for higher affinity to duplexes.
Duplicate Claim Warning
Applicant is advised that should claims 1 be found allowable, claim 29 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. Should claims 7-9 be found allowable, claim 26-28 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. It is noted that the recitation of composition does not include any additional limitations to the claimed amino acid sequence or nucleic acid sequence and as such are duplicates to the isolated nucleic acid and amino acid. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Conclusion
No claims are allowable. It is noted that there is no corrected power of attorney in the case, which would be required for interview or discussion of allowable subject matter.
However an amendment to the claims to recite the following would place the claims in condition for allowance:
Cancel claims 2-3, 10-15, 17-25
1. A kit comprising a RNA:DNA hybrid binding protein, referred to as an epiprinter molecule, comprising at least one RNA:DNA hybridization hybrid-binding domain (HBD) and at least one reactive moiety, wherein the epiprinter molecule comprises the amino acid sequence selected from the group consisting of SEQ ID NO:8, SEQ ID NO:14, SEQ ID NO:16, and SEQ ID NO:19 and instructions for use.
2-6. cancel
7. A kit comprising a nucleic acid sequence encoding an epiprinter molecule and instructions for use, wherein the nucleic acid sequence is selected from the group consisting of SEQ ID NO:7, SEQ ID NO:13, SEQ ID NO:15, and SEQ ID NO:18
8-9. cancel
16. A system for detection a molecule of interest comprising at least one epiprinter molecule of claim 1, at least one epitape molecule, wherein the epitape molecule comprises a nucleotide sequence complementary to a nucleotide sequence of the target of interest, and a nanopore detection system comprising a first reservoir containing an electrically conductive aqueous solution; an electrode disposed within the first reservoir in electrical contact with the electrically conductive aqueous solution; a second reservoir containing an electrically conductive aqueous solution; another electrode disposed within the second reservoir and in electrical contact with the electrically conductive aqueous solution; and a membrane separating the two reservoirs, the membrane having a pore through which the epiprinter and nucleic acid sequence can pass.
26. An isolated nucleic acid molecule comprising a nucleotide sequence encoding an RNA:DNA hybrid binding molecule comprising at least one RNA:DNA hybrid binding domain, wherein the nucleic acid molecule comprises the sequence selected from the group consisting of SEQ ID NO:7, SEQ ID NO:13, SEQ ID NO:15, and SEQ ID NO:18 and instructions for use.
27. cancel
28. cancel
29. (Currently amended) A RNA:DNA hybrid binding molecule comprising at least one RNA:DNA hybrid binding domain, wherein the molecule comprises the amino acid sequence selected from the group consisting of SEQ ID NO:8, SEQ ID NO:14, SEQ ID NO:16 and SEQ ID NO:19.
30. A method of binding at least one RNA:DNA hybrid binding molecule to a target sequence, the method comprising contacting a sample comprising a target sequence with an RNA:DNA hybrid binding molecule of claim 29 and binding the target sequence to the RNA:DNA hybrid binding molecule.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAE L BAUSCH whose telephone number is (571)272-2912. The examiner can normally be reached M-F 9a-4p.
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, Fereydoun Sajjadi can be reached at 571-272-3311. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SARAE L BAUSCH/Primary Examiner, Art Unit 1699
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