DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. 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
2. Applicant’s election without traverse of Invention II in the reply filed on September 15, 2025 is acknowledged.
Claims 1-7 are currently pending.
Claims 1 and 7 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on September 15, 2025.
Priority
3. Acknowledgment is made of applicant's claim for foreign priority based on applications filed in China on February 16, 2022. It is noted, however, that the foreign priority date is the effective filing date of the claimed invention IF
-the foreign application supports the claimed invention under 112(a), AND
-the applicant has perfected the right of priority by providing
-a certified copy of the priority application, and
-a translation of the priority application (if not in English).
In the instant case Applicant has not perfected the right of priority by providing a translation of the priority application. The effective filing date of the Application is considered to be December 29, 2022 which is the filing date of US Application 18/148,062.
Claim Rejections - 35 USC § 101
4. 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.
5. Claims 2-6 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter. The claims are drawn to “An application of reagents for detecting biomarkers in a sample for preparing diagnostic tools of CARAS”. The claims appear to be directed to a process without setting forth any steps involved in the process. Claims that do not purport to claim a process, machine, manufacture, or composition of matter fail to comply with 101. See MPEP 2173.05(q).
6. Claims 2-6 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception without significantly more. The claims have been evaluated using the 2019 Revised Patent Subject Matter Eligibility Guidance (see Federal Register Vol. 84, No. 4 Monday, January 7, 2019).
Step 1: The claims are directed to the statutory category of a process.
Step 2A, prong one: Evaluate Whether the Claim Recites a Judicial Exception
The instant claims recite a law of nature. The claims are drawn to “An application of reagents for detecting biomarkers in a sample for preparing diagnostic tools of CARAS, the biomarkers comprising circ_0070934, MGAT3, miR-199a-5p”. The claims recite a correlation between circ_0070934, MGAT3, miR-199a-5p and CARAS (combined allergic rhinitis and asthma syndrome). This type of correlation is a consequence of natural processes, similar to the naturally occurring correlation found to be a law of nature by the Supreme Court in Mayo.
Step 2A, prong two: Evaluate Whether the Judicial Exception Is Integrated Into a Practical Application
The claims do NOT recite additional steps or elements that integrate the recited judicial exceptions into a practical application of the exception(s). For example, the claims do not practically apply the judicial exception by including one or more additional elements that the courts have stated integrate the exception into a practical application:
An additional element reflects an improvement in the functioning of a computer, or an improvement to other technology or technical field;
An additional element that applies or uses a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition;
An additional element implements a judicial exception with, or uses a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim;
An additional element effects a transformation or reduction of a particular article to a different state or thing; and
An additional element applies or uses the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological
environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception.
The claims do not recite any steps or elements in addition to the judicial exception. Thus the claims do not recite any steps or elements in addition to the judicial exception that integrate the judicial exception into a practical application.
Step 2B: Evaluate Whether the Claim Provides an Inventive Concept
The claims do not recite any steps or elements in addition to the judicial exception. Thus the claims do not recite any steps or elements in addition to the judicial exception that provide an inventive concept.
It is noted that the courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity.
Determining the level of a biomarker in blood by any means, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017);
Using polymerase chain reaction to amplify and detect DNA, Genetic Techs. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016); Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1377, 115 USPQ2d 1152, 1157 (Fed. Cir. 2015);
Detecting DNA or enzymes in a sample, Sequenom, 788 F.3d at 1377-78, 115 USPQ2d at 1157); Cleveland Clinic Foundation 859 F.3d at 1362, 123 USPQ2d at 1088 (Fed. Cir. 2017);
Analyzing DNA to provide sequence information or detect allelic variants, Genetic Techs., 818 F.3d at 1377; 118 USPQ2d at 1546;
Amplifying and sequencing nucleic acid sequences, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014)
For the reasons set forth above the claims are not directed to patent eligible subject matter.
Claim Rejections - 35 USC § 112(b)
7. 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 2-6 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.
Claims 2-6 are rejected because the claims are generally narrative and indefinite, failing to conform with current U.S. practice. They appear to be a literal translation into English from a foreign document and are replete with grammatical and idiomatic errors.
Claims 2-6 are drawn to “An application of reagents for detecting biomarkers in a sample for preparing diagnostic tools of CARAS”. Claims 2-6 are indefinite because they attempts to claim a process without setting forth any steps involved in the process. See MPEP 2173.05(q).
Claims 2-6 are indefinite over the recitation of “circ_0070934”. This recitation refers to a circular RNA molecule. In the instant case, the sequence of “circ_0070934” is not disclosed in the claim or the specification and one of ordinary skill in the art would not know the sequence of “circ_0070934”. While the specification discloses primers that amplify “circ_0070934” (SEQ ID NOs: 3-4), the complete sequence of “circ_0070934” is not provided. Therefore one of skill in the art would not be able to determine the metes and bounds of the claimed subject matter so as to avoid infringement.
Claim 3 is rejected over the recitation of the phrase “reagents for detecting expression levels of the biomarkers in the sample by sequencing technology, nucleic acid hybridization technology, nucleic acid amplification technology and protein immunization technology”. In the instant case sequencing technology, nucleic acid hybridization technology, nucleic acid amplification technology are known in the art as ways to detect expression. However the claims are confusing because it is unclear how protein immunization technology is used to detect expression. Further it is unclear if the claims require reagents for each of the recited technologies or if the claim only requires reagents for one of the recited technologies. Clarification is required.
Claims 4 and 5 are rejected because the recite “primer pairs, probes or antisense nucleotides specifically combined with genes of the biomarkers; and antibodies, interacting proteins, ligands, nanoparticles or aptamers specifically bound to proteins or peptide fragments of the biomarkers”. These claims are confusing for numerous reasons. First it is unclear what it means to be “specifically combined with genes of the biomarkers”. Does this mean that the recited primer pairs, probes or antisense nucleotides have the capability of hybridizing to genes of the biomarkers or that they are actually hybridized? Further it is noted that genes are segments of DNA. Therefore it is unclear if the reagents are used to detect the DNA molecules that encode the biomarkers or the biomarkers themselves? At least two of the biomarkers are RNA molecules (circ_0070934 and miR-199a-5p). Further it is unclear what it means to be “specifically bound to proteins or peptide fragments of the biomarkers”. Does this mean that the recited antibodies, interacting proteins, ligands, nanoparticles or aptamers have the capability of binding to the proteins/peptides or that they are actually bound to them? Further it is noted that at least two of the biomarkers do not even encode for proteins/peptides (circ_0070934 and miR-199a-5p). Clarification is required.
Claim 5 states that “the primer pair specifically bound to MGAT3 comprises sequences as shown in SEQ ID NO: 1-2; the primer pair specifically bound to miR-199a-5p comprises a sequence as shown in SEQ ID NO: 5; and the primer pair specifically bound to circ_0070934 comprises sequences as shown in SEQ ID NO: 3-4”. This language is considered indefinite because it is unclear what “sequence(s) as shown in” means. For example it is unclear if the primer pair is only required to have fragments of the sequences found within SEQ ID NOs: 1 and 2 or if they are required to have the full length sequences. If it is the later it is unclear if this language is open ended or closed. For example if the primer was meant to be limited to the nucleotides of SEQ ID NO: 1 then this rejection can be overcome by amending the claims to recite i.e., “a first primer consisting of the nucleotide sequence of SEQ ID NO: 1". If the primer was meant require the nucleotides of SEQ ID NO: 1 plus any number of additional nucleotides on either side, then this rejection can be overcome by amending the claims to recite i.e., “a first primer comprising the nucleotide sequence of SEQ ID NO: 1". Clarification is required.
Claim 6 recites “wherein the sample comprises biopsy, curettage, blood, urine, saliva, cell culture, mucous membrane samples, feces, intestinal lavage, joint fluid, cerebrospinal fluid, bile samples, respiratory secretions and bronchoalveolar lavage fluid samples”. The claim is confusing because it is unclear if the claim requires a sample with all of the listed samples types mixed together (in view of the recitation of “and”) or if the claim only requires one of the recited sample types. Clarification is required.
Claim Rejections - 35 USC § 102
8. 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.
9. Claims 2, 3, and 6 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yick (Eur Respir J 2013 Vol 42 pages 662-670).
Yick teaches that they examined the difference in transcriptomic profiles between asthma and controls. This cross-sectional study compared four steroid-free atopic asthma patients and five healthy nonatopic controls. Total RNA from four biopsies per subject was prepared for RNA-Seq (abstract). Yick teaches that four endobronchial biopsies per subject were collected and frozen after overnight incubation in RNAlater (Qiagen, Venlo, The Netherlands). TRIzol (Invitrogen, Carlsbad, CA, USA) was used to isolate RNA. Amplified cDNA was prepared with the Ovation RNA-Seq System (NuGEN, San Carlos, CA, USA) and cDNA libraries were constructed using SPRIworks Fragment Library System II (Beckman-Coulter, Brea, CA, USA). Emulsion-based clonal amplification was performed using the GS FLX Titanium emPCR Kit Lib-L (Roche, Penzberg, Germany) to prepare enriched DNA library beads for sequencing on the GS FLX+ System (454; Roche) (pages 663-664 and Fig 1). Yick teaches that sequencing reads where distributed throughout the whole transcriptome (page 669). Thus Yick teaches an application of reagents (the kits) for detecting gene expression by RNA-Seq in a sample. It is a property of the method of Yick that it would detect biomarkers comprising circ0070934, MGAT3, and miR-199a-5p since it sequences the entire transcriptome. Yick teaches a method that relies on sequencing technology. Yick teaches biopsy samples.
10. Claims 2-6 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yujie (Journal of Nanjing Medical University Natural Sciences September 2022, 42(9):1279-1286).
Yujie teaches that thirty-eight patients with CARAS and 43 healthy controls were collected, and the level of MGAT3 protein in plasma was detected by ELISA, and the expression level of circ_0070934/miR-199a-5p/MGAT3 in peripheral blood was detected by qRT-PCR. Yujie teaches that ELISA results showed that the concentration of MGAT3 in CARAS patients was significantly lower than that in the control group (P =0.035). qRT-PCR results showed that the expression of circ_ 0070934 (P = 0.001) and MGAT3 (P < 0.001) was down-regulated compared with that of the control group, while the expression level of miR-199a-5p was up-regulated (P =0.013) (abstract). Yujie teaches that the human MGAT3ELISA kit (Shanghai Kexing Biotechnology Co., Ltd.) detected the content of MGAT3 in serum samples of CARAS patients and control groups. Yujie teaches performing qRT-PCR to detect circ_0070934/miR-199a-5p/MGAT3. The primer sequence is as follows:
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These are the same primers shown in SEQ ID NOs: 1-5. Thus Yick teaches an application of reagents (antibody and primers) for detecting expression of circ0070934, MGAT3, and miR-199a-5p in a blood sample by nucleic acid technology.
11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMANDA HANEY whose telephone number is (571)272-8668. The examiner can normally be reached Monday-Friday, 8:15am-4:45pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Shen can be reached at 571-272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/AMANDA HANEY/Primary Examiner, Art Unit 1682