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 with traverse of the invention of Group 2 (methods comprising detecting a serum circRNA) in the reply filed on 06/01/2026 is acknowledged. The traversal is on the ground(s) that there is not a search burden to examine the non-elected products in addition to the elected methods. This is not found persuasive because the instant application is a 371 national stage application of a PCT, and thus the relevant issue is unity of invention, which is lacking as detailed in the requirement of 04/01/2026.
The requirement is still deemed proper and is therefore made FINAL.
Applicant’s additional election (species election) of the combination of hsa_circ_0003568 and hsa_circ_0000945, and the combination of primers that is SEQ ID NO: 3-6, reply filed on 06/01/2026 is acknowledged. In light of the Examiner’s search of the elected combinations, the species election requirement set forth between the elected circular RNA combination and the particular circular RNA that is hsa_circ_0000945 is withdrawn, and the species election requirement set forth between the elected primer combination and the particular primer that is SEQ ID NO: 5, are withdrawn. The examined claims thus include the embodiments of the combinations of the two recited circular RNAs and the four primers, and the particular circular RNA that is hsa_circ_0000945 and the particular primer that is SEQ ID NO: 5.
Claims 1, 2, and 6-10 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 06/01/2026.
Claim Rejections - 35 USC § 112 - Indefiniteness
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 3-5 and 11-12 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 3-5 and 11-12 are unclear over recitation of the limitation “the reagent is in a preparation of an auxiliary diagnosis reagent for examining craniosynostosis” because it is unclear what is required for any reagent to be part of “an auxiliary diagnosis reagent”. Neither the claims, the disclosure of the instant application, nor the related art provide any particular elements that must be included, or specifically may be excluded, from any collection of products or reagents such that collection is “an auxiliary diagnosis reagent for examining craniosynostosis”. In the instant case the claims are examined in so far as any reagents that can perform the recited “detecting” are considered “an auxiliary diagnosis reagent for examining craniosynostosis”.
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.
Claims 3, 4, 11 and 12 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea and a natural phenomenon without significantly more.
The claim(s) recite(s) “a serum circRNA marker associated with craniosynostosis”, “serum circRNA marker associated with craniosynostosis”, and a “diagnosis reagent for examining craniosynostosis”. Where the claims are directed to an recognition of an association between the marker and craniosynostosis, the claims are directed to an abstract idea that is a mental process (i.e.: the evaluation of data or information about a marker to reach a conclusion about a phenotype, which can be performed in the human mind) (MPEP 2106.04(a)(2)(III)). Additionally, where the claims recite an asserted association between hsa_circ_0003568, hsa_circ_0000945, and craniosynostosis, the claims are directed to a natural phenomenon (MPEP 2106.04(b)) which is the association of the presence of naturally occurring biomolecules with a phenotype.
This judicial exception is not integrated into a practical application because there are no particular practical steps that are taken or performed as a result of the detecting of a circular RNA marker (MPEP 2106.04(d)). The claims end with the detection of the naturally occurring RNA.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the steps of the claims are well-understood, routine and conventional activity related to the analysis of circular RNAs, and are recited at a high level of generality in the rejected claims. The claims are broadly directed to the detection of hsa_circ_0003568 and hsa_circ_0000945. The rejected claims require no particular specific reagents, and in this regard it is noted that the prior art teaches that comprehensive analysis of circular RNA content in serum samples using RNA-seq, the Agilent Human CircRNA Array (V2.0), and RT-qPCR was well-understood, routine and conventional activity prior to the effective filing date of the instant claims; e.g.: Xie et al (2020) and Huang et al (2019).
Claim Rejections - 35 USC § 102
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.
Claim(s) 3, 4 and 12 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mellios (US PG Pub 2021/0079474 A1; Mar. 18, 2021).
Mellios teaches methods for detection circular RNA biomarkers. Relevant to the rejected claims, Mellios teaches that samples for circRNA biomarker detection may be serum (e.g.: para 0076), and that biomarkers may be detected using primer-based detection methods including amplification with primers and qRT-PCR (e.g.: para 0081-0082). Mellios teaches that hsa_circ_0000945 (comprising chr19:48248829-48248993) is a biomarker for schizophrenia (SCZ) (e.g.: para 0058-0063; Table 2 on p.29).
Claim Rejections - 35 USC § 103
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.
Claim(s) 3, 4, 5 and 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mellios (US PG Pub 2021/0079474 A1; Mar. 18, 2021) in view of Human Genome Assembly GRCh37 (02/27/2009) as evidenced by the provided sequence alignment.
Mellios teaches methods for detection circular RNA biomarkers. Relevant to the rejected claims, Mellios teaches that samples for circRNA biomarker detection may be serum (e.g.: para 0076), and that biomarkers may be detected using primer-based detection methods including amplification with primers and qRT-PCR (e.g.: para 0081-0082). Mellios teaches that hsa_circ_0000945 (comprising chr19:48248829-48248993) is a biomarker for schizophrenia (SCZ) (e.g.: para 0058-0063; Table 2 on p.29). Thus Mellios anticipates the detection of hsa_circ_0000945 using primer based methods, and discloses that hsa_circ_0000945 comprises chr19:48248829-48248993.
Mellios does not explicitly disclose the particular nucleotide sequence of hsa_circ_0000945 (i.e.: chr19:48248829-48248993), however the relevant chromosome sequence was known in the prior art and is provided in the Human Genome Assembly GRCh37.
The GRCh37 is a prior art disclosure of the human genome, which includes positions 48248829-48248993 of chromosome 19 which are identical to SEQ ID NO: 2 of the instant application and include the sequence set forth SEQ ID NO: 5 (i.e.: the forward primer) of the instant application (noted by the overlining arrow):
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It would have been prima facie obvious to someone with ordinary skill in the relevant art before the effective filing date of the rejected claims to have used a primer having the sequence of SEQ ID NO: 5 for the detection of hsa_circ_0000945 using the methods of Mellios. The skilled artisan would have been motivated to use a primer for circRNA detection based on the expressed teachings of Mellios that qRT-PCRs require the use of primers which are specifically designed to hybridize to and amplify a sequence of interest (e.g.: para 0082) and that primers are used to amplify the splice junction region of a circular RNA (e.g: para 0086). The skilled artisan would have a reasonable expectation of success in using a primer including SEQ ID NO: 5 based on the presence of the required sequence in the prior art disclosure of the GRCh37 assembly.
Claim(s) 3, 4, 11 and 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mellios (US PG Pub 2021/0079474 A1; Mar. 18, 2021) in view of Xie et al (2020)
Mellios teaches methods for detection circular RNA biomarkers. Relevant to the rejected claims, Mellios teaches that samples for circRNA biomarker detection may be serum (e.g.: para 0076), and that biomarkers may be detected using primer-based detection methods including amplification with primers and qRT-PCR (e.g.: para 0081-0082). Mellios teaches that hsa_circ_0000945 (comprising chr19:48248829-48248993) is a biomarker for schizophrenia (SCZ) (e.g.: para 0058-0063; Table 2 on p.29). Thus Mellios anticipates the detection of hsa_circ_0000945 using primer based methods, and discloses that hsa_circ_0000945 comprises chr19:48248829-48248993.
Mellios does not explicitly disclose the extraction serum RNA from serum, however the steps of obtaining serum and isolating RNA from serum for circular RNA analysis were known in the prior art and art taught by Xie et al..
Xie et al teaches the analysis of circular RNAs found in serum of human subjects and teaches steps related to obtaining the RNAs including the isolation of serum from blood samples and the extraction of RNA from the serum (e.g.: p.9 – Clinical samples; p.10 – Serum and preparation).
It would have been prima facie obvious to someone with ordinary skill in the relevant art before the effective filing date of the rejected claims to have collected serum from blood samples and isolate RNA from the serum (as taught by Xie et al) to obtain a sample for the detection of hsa_circ_0000945 using the methods of Mellios. The skilled artisan would have been motivated to use, and would have a reasonable expectation of success in using, the methods of Xie et al based on the expressed teachings of Xie et al that such methods provide samples from which circular RNA targets can be analyzed, and based on the expressed teachings of Mellios that circRNA biomarkers can be analyzed in serum samples.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEPHEN THOMAS KAPUSHOC whose telephone number is (571)272-3312. The examiner can normally be reached M-F, 8am-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Anne Gussow can be reached at 571-272-6047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Stephen Kapushoc
Primary Examiner
Art Unit 1683
/STEPHEN T KAPUSHOC/Primary Examiner, Art Unit 1683
Prosecution Insights