DETAILED CORRESPONDENCE
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 .
This action is in response to the papers filed August 11, 2026. Currently, claims 14-15, 18-21, 23-33 are pending. Claims 29-33 have been withdrawn from consideration as directed to non-elected subject matter.
All arguments have been thoroughly reviewed but are deemed non-persuasive for the reasons which follow. This action is made FINAL.
Any objections and rejections not reiterated below are hereby withdrawn.
The 101 rejection has been withdrawn in view of the amendments to Claim 14 to include the limitations of previous Claim 16.
The 112B rejections have been withdrawn in view of the amendments to the claims.
The 102 rejections have been withdrawn in view of the amendments to the claims to require fluorescent labels and quenchers and the transitional phrase comprising.
Priority
This application is a 371 of PCT/CN2021/110526 filed August 4, 2021.
Election/Restrictions
Applicant's election without traverse of Group I, Claims 14-27 in the paper filed March 8, 2026 is acknowledged.
The requirement is still deemed proper and is therefore made FINAL.
Claim Rejections - 35 USC § 112- Second Paragraph
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.
Newly amended Claims 18-19, 23 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 pre-AIA the applicant regards as the invention.
Claims 18-19 and 23 are indefinite over the recitation wherein “the fluorescent labeling group” because Claim 14 requires different fluorescent labeling groups for the two different probes. Thus, it is unclear which fluorescent labeling group is being referred to or whether each of the fluorescent labeling groups are selected from the alternatives in Claim 18-19 and 23. The claims are not limited to a single “the fluorescent labeling group”. Clarification is required.
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.
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 14-15, 18-19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sarkar et al. (J. or Ethnopharmacology, Vol. 140, pages 443-446, 2012) in view of Meiler et al. (J. Exp. Med. Vol. 205, No. 12, pages 2887-2898, November 2008) and further in view of Rae et al. (Genbank Accession AF026261, January 7, 1998) and Untergasser et al. (Primer3Plus, an enhanced web interface to Primer3, Nucleic Acids Research, 2007, Vol. 35, 2007).
Sarkar teaches primers for the Human H1 mRNA and GAPDH (as an internal standard). With the assistance of Primer Express (Applied Biosystems, Foster City, CA, USA) the Human H1 mRNA sense primer (5′-CAGAGGATCAGATGTTAGGTGATAGC-3′), anti-sense primer (5′-AGCGGAGCCTCTTCCAAGTAA-3′) and probe (FAM-CTTCTCTCGACGGACTCAGATACCACC-TAMRA) were chosen.
Meiler et al. teaches real time PCR of HR1. Meiler teaches the PCR primers and probes were designed based on sequence from GenBank including NM_001098213. The primers and probe are:
HR1 forward, 5′-TCTCGAACGGACTCAGATACCA-3′;
HR1 reverse, 5′-CCTGTGTTAGACCCACTCCTCAA-3′;
HR1 probe, FAM-ACAGAGACAGCACCAGGCAAAGGCAA-TAMRA;
The composition included using SYBR-PCR Master Mix and TaqMan RT reagents with random hexamers. The TaqMan RT kit comprises buffer, Taq enzymes, reverse transcriptase etc (limitations of Claim 27).
Sarkar nor Meiler specifically teach the primers and probes comprising SEQ ID NO: 1-6 for HRH1 and GAPDH.
However, Rae teaches the histamine receptor H1 polynucleotide. Rae teaches a 1464 bp sequences that comprises SEQ ID NO: 1, 2, and 3 of the instant application.
SEQ ID NO: 1 is position 1067-1087; SEQ ID NO: 2 is 1131-1150 and SEQ ID NO: 3 is 1104-1124.
A skilled artisan at the time of filing would have designed primers and probes to known sequences (such as the sequences disclosed in the above references) with a high expectation of success. An alignment of primers 1, 2 and probe 3 are aligned to the sequence and aligned to Sarkar and Meiler. It is clear that the primers overlap the primers known in the art.
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To design such primers constituted routine and conventional optimization at the time of filing. See In re Aller, 220 F.2d 454, at 456 (CCAP 1955) (“where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.”). Sarkar and Meiler teach the primers were designed with the assistance of primer express, a commercially available program for designing primers. Further, numerous references describe how to design and optimize primers and probes for PCR applications. For example, Untergasser teaches how to design primers and probes from known sequences using known online primer/probe design programs for use in PCR assays. Untergasser teaches how to use Primer3Plus online program to design primers and probes to known sequences (Untergasser at pgs. W71-74). In other words, Untergasser provides specific guidance and parameters to optimize primer, probe and PCR assay design to yield optimal results; thus, designing PCR assays for particular applications constitutes well-known routine optimization. Selection of specific oligonucleotides for specific Tm represents routine optimization with regard to sequence, length and composition of the oligonucleotide. Such optimization parameters are explicitly recognized in Untergasser. As noted in In re Aller, 105 USPQ 233 at 235, where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. Routine optimization is not considered inventive and no evidence has been presented that the primer selection performed was other than routine, that the products resulting from the optimization have any unexpected properties, or that the results should be considered unexpected in any way as compared to the closest prior art.
Thus, the instant sequences are clearly a functional homologue of the above similar primers based on the known HRH1 sequence. This is supported by In Re Deuel, 34 USPQ 2d 1210 (Fed. Cir. 1995), in which the Court of Appeals for the Federal Circuit stated that (emphasis added).
Normally, a prima facie case of obviousness is based upon structural similarity, i.e., an established structural relationship between a prior art compound and the claimed compound. Structural relationships may provide the requisite motivation or suggestion to modify known compounds to obtain new compounds. The claimed sequences were structural homologs of the sequences disclosed in the prior art, and concerning which a biochemist of ordinary skill would attempt to obtain alternate compounds with improved properties. Therefore, the claimed sequences are prima facie obvious over the cited references in the absence of secondary considerations.
The ordinary artisan would have had a reasonable expectation of success that such primers generated using known sequences as taught by Sarkar and Meiler to detect the same HRH1 because the claimed probes are functional equivalents of the sequences. The ordinary artisan would have been motivated to generate a number of said primers to the same HRH1 sequence to provide flexibility and optimize experimentation (see Untergasser). Selection of specific oligonucleotides for specific Tm represents routine optimization with regard to sequence, length and composition of the oligonucleotide. Such optimization parameters are explicitly recognized in Untergasser. As noted in In re Aller, 105 USPQ 233 at 235, where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. Routine optimization is not considered inventive and no evidence has been presented that the primer selection performed was other than routine, that the products resulting from the optimization have any unexpected properties, or that the results should be considered unexpected in any way as compared to the closest prior art.
In sum, the claimed primers are prima facie obvious because there was clear motivation to design PCR primers to detect the same HRH4 sequence; and designing and optimizing such primers constitutes a well-known, routine and conventional technique which would yield the claimed primers with a reasonable expectation of success.
Applicants should submit secondary evidence of non-obviousness in line with MPEP §§ 716.01-716.02 (e.g. unexpected results evidence).
With respect to Claim 16-19, the probes of Sarkar and Meiler each comprise FAM and TAMARA. It would have been prima facie obvious to have differentially labeled the probes to allow for differential detection.
Response to Arguments
The response traverses the rejection. The response asserts the references cited do not teach the claimed invention. This argument has been considered but is not convincing for the reasons set forth in the rejection above. The response does not point to any particular limitations that are not rendered obvious by the cited references.
The response argues secondary consideration and points to Example 1, Figure 6, Table 6 of the application. This argument has been reviewed but is not persuasive. The response does not demonstrate the showing in the specification is a comparison to the closest prior art (716.02(e)). As noted in the rejection above, the primers of Meiler and Sarkar are directed to the same region as the claimed primers/probe. The primers of SEQ ID NO: 7-9 are not the closest prior art. Primer 7 is upstream of SEQ ID NO:1 about 120bp.
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The primers of Meiler and Sarkar are overlapping or immediately upstream. Thus, the comparison in the specification is not the closest prior art.
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Furthermore, the claims are directed to comprising SEQ ID NO: 1-3. The results in the specification are directed to primers consisting of SEQ ID NO: 1-3. The results argued by the response to show secondary considerations are not commensurate in scope with the claimed invention (see MPEP 716.02(d)).
The response argues improper hindsight was used to formulate the rejection. This argument has been reviewed but is deemed non persuasive. As provided in MPEP 2145 "[a]ny judgment on obviousness is in a sense necessarily a reconstruction based on hindsight reasoning, but so long as it takes into account only knowledge which was within the level of ordinary skill in the art at the time the claimed invention was made and does not include knowledge gleaned only from applicant’s disclosure, such a reconstruction is proper." In reMcLaughlin, 443 F.2d 1392, 1395, 170 USPQ 209, 212 (CCPA 1971). See MPEP § 2141 and § 2143 for guidance regarding establishment of a prima facie case of obviousness.
Thus for the reasons above and those already of record, the rejection is maintained.
Claims 20-21, 23-28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sarkar et al. (J. or Ethnopharmacology, Vol. 140, pages 443-446, 2012) in view of Meiler et al. (J. Exp. Med. Vol. 205, No. 12, pages 2887-2898, November 2008) and further in view of Rae et al. (Genbank Accession AF026261, January 7, 1998) and Untergasser et al. (Primer3Plus, an enhanced web interface to Primer3, Nucleic Acids Research, 2007, Vol. 35, 2007) and further in view of Asuragen (WO 2016/138376, September 1, 2016).
Neither Sarkar, Meiler, Rae nor Untergasser teaches combining the claimed probes and primers into a kit comprising ROX, enzymes, PCR reaction solutions and standards.
However, Zeigler teaches a kits comprising primers, probes, ROX, standard core reagents, Taq, buffer mastermix, diluent (para 97).
Therefore, it would have been prima facie obvious prior to the effective filing date of the claimed invention to have packaged primers, probes in kits with the necessary reagents to detect nucleic acids. The art is replete with kits comprising primers, probes, PCR reaction solutions, enzyme solutions, standards, ROX and nuclease-free water. The ordinary artisan would have been motivated to have added PCR solutions, enzyme solutions, ROX, standards in a kit with the HRH1 and GAPDH probes and primers to allow the ordinary artisan a convenient kit.
Response to Arguments
The response traverses the rejection. The response asserts rejection is overcome for the reasons provided above. This argument has been considered as discussed above.
Thus for the reasons above and those already of record, the rejection is maintained.
Conclusion
No claims allowable.
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.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Nguyen et al. (Molecular Pharmacology, Vol. 59, No. 3, pages 427-433, 2001) teaches characterization of the H4 receptors. Figure 1 provides an alignment of the histamine receptors H1-H4. Nguyen teaches amplifying three overlapping fragments (A, B, and C) and provides the primers.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEANINE ANNE GOLDBERG whose telephone number is (571)272-0743. The examiner can normally be reached Monday-Friday 6am-3:30pm.
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, Wu-Cheng (Winston) Shen can be reached on (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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/JEANINE A GOLDBERG/Primary Examiner, Art Unit 1682
September 29, 2026
