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 .
DETAILED ACTION
This response is based upon papers filed 3/16/2026.
3. Applicant's election without traverse of Group I and the species of the combination of genes in table 1 (SEQ ID No. 1-398) and the combination of primers in table 2 (SEQ ID no 399-1194) in the reply filed on 8/23/2023 is acknowledged. It is noted that the election is deemed to be free of the art and 35 USC 112. Namely the interpretation that Claim 21 requires all of SEQ ID NO. 399-1194 would be in condition for allowance. Therefore the examiner will move to the next species. The next species that is searched is one primer pair and one gene from the list of genes.
4. Claims 21-32, 34-35 are pending. Claims 1-20, 33 are cancelled.
5. The following rejections are maintained with response to arguetmsn following.
6. This action is FINAL.
Withdrawn Rejection
The 35 USC 112b made in the previous office action is withdrawn based upon amendments to the claims.
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(s) 21-25,31-32,34 is/are rejected under 35 U.S.C. 103 as being unpatentable over Alarcon et al. (US Patent Publication 2015/0024952 Jan 22, 2015) in view of Dieffenbach (PCR methods and Applications (1993) volume 3, pages S30-S37), Roux et al(PCR Methods and Applications (1995) volume 4, pages s185-s194) and Stapleton et al (US Patent Application 2016/0152972 June 2, 2016).
With regard to claim 21, Alarcon et al. teaches a method of measuring mRNA expression of VEGFA and CD33 expression in a human and comparing the expression to a control to determine changes in expression (para 264). Alacon et al. teaches that RT PCR in a multiplex is used for expression detection (para 264). Alacon et al. teaches further measuring a housekeeping gene (para 136). As such, Alarcon et al. teaches detection of one of the genes associated with immune response activity. However, Alacon et al. does not teach the primer pairs of VEGFA and CD33 as recited in the claims.
With regard to claim 21, the instant specification detection that uracil DNA glycosylase (UDG or UNG) can be consider a non-native nucleotide that is cleaved (para 138). Alacrcon et al. teaches that the multiplex design is made with UDG (para 500), but does not teach that these are on the primer pairs.
With regard to claim 22, Alarcon teaches that these genes are associated with tumor markers (para 264).
With regard to claims 23-24, Alarcon et al. teaches a method of measuring mRNA expression of VEGFA and CD33 expression (para 264).
With regard to claim 25, as Alarcon et al. teaches measuring expression of the genes of CD33 and VEGFA these genes would encompass the target sequences of the recited sequences directed to these genes.
With regard to claim 31, Alacon et al. teaches that the biological sample can comprise tumor (11).
With regard to claim 32, Alacon et al. teaches that the sample and the control can be from the same individual (para 124).
With regard to claim 34, Alacon et al. teaches that the expression level is normalized against a housekeeping gene (para 124).
However, Alacon et al. does not teach the primer pairs of VEGFA as recited in the claims.
With regard to claim 21, although Alacon et al. does not teach a pair of primers and the target sequences, the prior art teaches that these would be well known, Dieffenbach and Roux et al. teach constraints to designing oligonucleotides. Dieffenbach teaches parameters and principles of promoter design include primer length, terminal nucleotide, GC content, melting temperature, PCR product length, and placement of target sequence (s30-s34). Dieffenbach teaches PCR software was known (s35).
Roux teaches optimization of PCR by the presence of enhancing agents, Mg2+, annealing temperature, primer design, cycle number, hot start PCR (s185-s194).
With regard to claim 21, the art teaches that UDG can be added to the ends of primers for a cleavable site. Stapleton et al teaches that in multiplex RT PCR primers can be designed with an uracil on the ends and cleaved (para 10 and 104. 326 and 331).
Designing oligonucleotides to hybridize to specific targets, which are equivalents to those taught in the art is routine experimentation. The prior art teaches the parameters and objectives involved in the selection of oligonucleotides that function as primers, see Dieffenbach and Roux. The prior art is replete with guidance and information necessary to permit the ordinary artisan in the field of nucleic acid detection to design primers. As discussed above, the ordinary artisan would be motivated to have designed and tested oligonucleotides from VEFGA and CD33 to obtain additional oligonucleotides that function to detect expression and identify oligonucleotides with improved properties for such detection. Furthermore the ordinary artisan would be motivated to add uracil to increases the efficiency of the primer amplification (para 326 Stapleton et al). Thus, for the reasons provided above, the ordinary artisan would have designed additional oligonucleotides using the teachings in the art at the time the invention was made including oligonucleotides that comprise the primers pairs for each gene. As such the recited oligonucleotides are obvious over the cited prior art, absent secondary considerations
Response to Arguments
The reply traverses the rejection. A summary of the arguments is provided below with response to arguments following. The reply asserts that the UDG used in the assay is used in the PCR product and not included in the primers (p. 8). The reply asserts that none of the cited art teach deoxyuracil (p. 9-10). The reply asserts that that there were multiple statements for the use, but does not teach use of deoxyuracil for destroying primer cotiaing amplification artifacts by cleaving the non-native nucleotides cleavable group (p. 10-11). The reply asserts that there is no one primer pair but rather “one or more housekeeping genes” and “a plurality of target sequence of genes associated with immune response activity comprising at least one of each of the following ….” (p 11-12). These arguments have been reviewed but have not been found persuasive. It is noted that the claims are not limited to primers comprising UDG, but rather that the primer pair reagents comprising a target specific region that includes at least one nucleotide that is a non-native nucleic clearable group:” Stapleton teaches uracil on the ends, but the reply asserts that it does not teaches the use for the “non-native nucleotide cleavable….”. The reply asserts that the art used does not teach the destroying step. However, the are teaches cleaving which would have the intended result of destroying. The step only requires cleaving, and as such the art teaches the breadth of the step of destroying. Further, the reply arguetmsn the species. It is noted that the claims require “one or more housekeeping genes” Alacon et al. teaches further measuring a housekeeping gene (para 136) The second requirement is that there is a “plurality of target sequences of genes associated with immune response activity comprising at least one of each…”. The targets is describe by the functions, however, the claim does not require that the genes have to be different for each of the functions nor does the specification limit the genes that would be encompassed by each function. Claim 23 provide a listing of genes and states that “genes associated with immune response activity are selected form the genes”. Alarcon et al. teaches a method of measuring mRNA expression of VEGFA and CD33 expression (para 264). These genes are encompassed by the list. As such these genes would encompass genes that have some association with each of the functions.
Claim(s) 30 is/are rejected under 35 U.S.C. 103 as being unpatentable over Alarcon et al. (US Patent Publication 2015/0024952 Jan 22, 2015) and Dieffenbach (PCR methods and Applications (1993) volume 3, pages S30-S37), Roux et al(PCR Methods and Applications (1995) volume 4, pages s185-s194) and Stapleton et al (US Patent Application 2016/0152972 June 2, 2016) as applied to claims 21-25, 31-32 and 34 and in view of Simmini et al. (US Patent Application Publication 2024/0376436 November 14, 2024).
Alarcon et al. teaches a method of measuring mRNA expression of VEGFA and CD33 expression in a human and comparing the expression to a control to determine changes in expression (para 264). Alacon et al. teaches that RT PCR in a multiplex is used for expression detection (para 264). Alacon et al. teaches further measuring a housekeeping gene (para 136). Dieffenbach and Roux teach the obviousness of using equivalent primer pairs to amplify genes of interest. Stapleton et al teaches UDG primers (para 326). As such, Alarcon et al. teaches detection of one of the genes associated with immune response activity.
Alacon et al. teaches that the expression level is normalized against a housekeeping gene (para 124) but does not teach TBP as a housekeeping gene.
With regard to claim 30, Simmini et al. teaches using the housekeeping of TBP for determination of mRNA expression levels (para 98).
Therefore it would be prima facie obvious to one of ordinary skill in the art at the time of the effective filing date to modify the housekeeping gene of Alacon et al. combination with TBP of Simmini et al. The ordinary artisan would be motivated to use one of the finite number of housekeeping genes of TBP as it shows the smallest standard deviation amongst panels of housekeeping genes (para 98).
Response to Arguments
The reply traverses the rejection. A summary of the arguments is provided below with response to arguments following. The reply asserts that the additional of Simmini does not overcome the deficiencies (p. 12-13). This argument has been reviewed but has not been found persuasive based upon the arguments set forth above.
Conclusion
No claims are allowed. It is noted that the combination of all SEQ ID Number 399-1194 appear to be free of the prior art. However, the examiner has not moved on to the next species in light of the rejections set forth above for the election.
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 KATHERINE D SALMON whose telephone number is (571)272-3316. The examiner can normally be reached 9-530.
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 5712723157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/KATHERINE D SALMON/ Primary Examiner, Art Unit 1682
Prosecution Insights