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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on March 26th, 2026 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
The Applicant states on Page 8 the Remarks filed March 30th, 2026 that no indication for consideration has been included for reference 22 listed on the PTO 1449. This reference was previously crossed out and not considered because it is in Japanese, which the Examiner cannot read. No translation of the reference has been provided. Therefore, it has not been considered.
Election/Restrictions - New - Necessitated by Addition of New Claims
Newly submitted claims 12 and 13 are directed to an invention that is independent or distinct from the invention originally claimed for the following reasons: the previously presented claims, along with newly introduced dependent claims, and claims 12 and 13 lack unity of invention because even though the inventions of these groups require the technical feature of the HLA gene amplification primer sets of claim 2, this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Xu, GenBank and Dieffenbach (see prior art rejection of claim 2).
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 12 and 13 are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Response to Amendment
The amendment filed March 30th, 2026 is acknowledged. Regarding the Office Action mailed December 29th, 2025:
The objections to the specification are withdrawn in view of the amendments.
The rejection set forth under 35 U.S.C. 112(b) is withdrawn in view of the amendments.
Maintained, modified, or new rejections are set forth below, as necessitated by the amendments. Responses to arguments, if necessary, follow their respective rejection sections.
Claim Summary
Claims 2-4 and 6-7 have been amended. Claims 1 and 5 have been canceled. Claims 8-17 have been added. Claims 2-4, 6-7, and 8-17 are pending. Claims 12 and 13 are withdrawn from consideration as being drawn to a non-elected invention/species. Claims 2-4, 6-7, and 8-11 and 14-17 are under examination and discussed in this Office action.
Claim Rejections - 35 USC § 112(b) - New - Necessitated by Amendment
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 3-4, 6-7, and 14-17 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 3-4, 6-7, and 14-17 all recite, or depend from claims that recite, the limitation "the one or more HLA gene primer sets”. There is insufficient antecedent basis for this limitation in the claims. Claim 2, from which all of these claims ultimately depend, introduces “one or more HLA gene amplification primer sets”, not “one or more HLA gene primer sets”. Therefore, the above cited claims are found indefinite.
Claim Rejections - 35 USC § 101 - Modified - Necessitated by Amendment
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 2-4, 6-11, and 14-17 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon consisting of a product of nature without significantly more. While the claims are directed to a composition of matter, a process, and products, and therefore meet step 1 of the subject matter eligibility test (see MPEP 2106.03), the claims recite primers SEQ ID NOs 1-12, which are considered products of nature. Further dependent claims are routine and conventional uses of primers, and therefore do not serve to integrate the judicial exception into a practical application. The full analysis of this determination is as follows:
Step 2A of the subject matter eligibility test requires a two-pronged analysis. Prong One asks: does the claim recite an abstract idea, law of nature or natural phenomenon? As discussed in MPEP 2106.04(II)(A)(1), the meaning of “recites” is “set forth” or “describes”. That is, a claim recites a judicial exception when the judicial exception is “set forth” or “described” in the claim. Part of Prong One is the markedly different characteristics analysis, which identifies product of nature exceptions. The first step of the markedly different characteristics analysis is to select the appropriate counterpart to the nature-based product. MPEP 2106.04(c)(II)(A) states, “When the nature-based product is derived from a naturally occurring thing, then the naturally occurring thing is the counterpart.” In the instant case, the claimed sequences of SEQ ID NOs 1-12 are described in the disclosure as being primers for human leukocyte antigen genes HLA-G, HLA-E, and HLA-F, which are capable of amplifying the entire length of the gene. Therefore, the closest counterpart to the claimed sequences is the corresponding gene sequence, and the claimed sequences are functionally identical. The second step of the markedly different characteristics analysis is to identify appropriate characteristics to compare. MPEP 2106.04(c)(II)(B) states, “Appropriate characteristics can be expressed as the nature-based product’s structure, function, and/or other properties, and are evaluated on a case-by-case basis.” In the instant case, the claimed sequences of SEQ ID NOs 1-12 are a genetic structure such as the nucleotide sequence of DNA. The final step in the markedly different characteristics analysis is to compare the characteristics of the claimed nature-based product to its naturally occurring counterpart in its natural state, in order to determine whether the characteristics of the claimed product are markedly different. The courts have emphasized that to show a marked difference, a characteristic must be changed as compared to nature, and cannot be an inherent or innate characteristic of the naturally occurring counterpart or an incidental change in a characteristic of the naturally occurring counterpart. Myriad, 569 U.S. at 580, 106 USPQ2d at 1974-75. In the instant case, there is nothing within the specification as filed that teaches the sequences of SEQ ID NOs 1-12 confer a change in characteristics such that each are markedly different from their naturally occurring counterpart. Since there is no evidence of change as compared to nature, the claims describe a natural phenomenon: the products of nature SEQ ID NOs 1-12.
Prong Two of the analysis under step 2A asks: does the claim recite additional elements that integrate the judicial exception into a practical application of the judicial exception? As discussed in MPEP 2106.04(II)(A)(2), “Because a judicial exception is not eligible subject matter, Bilski, 561 U.S. at 601, 95 USPQ2d at 1005-06 (quoting Chakrabarty, 447 U.S. at 309, 206 USPQ at 197 (1980)), if there are no additional claim elements besides the judicial exception, or if the additional claim elements merely recite another judicial exception, that is insufficient to integrate the judicial exception into a practical application. See, e.g., RecogniCorp, LLC v. Nintendo Co., 855 F.3d 1322, 1327, 122 USPQ2d 1377 (Fed. Cir. 2017) ("Adding one abstract idea (math) to another abstract idea (encoding and decoding) does not render the claim non-abstract"); Genetic Techs. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016) (eligibility "cannot be furnished by the unpatentable law of nature (or natural phenomenon or abstract idea) itself."). For a claim reciting a judicial exception to be eligible, the additional elements (if any) in the claim must "transform the nature of the claim" into a patent-eligible application of the judicial exception, Alice Corp., 573 U.S. at 217, 110 USPQ2d at 1981, either at Prong Two or in Step 2B.” The considerations to be used are set forth at MPEP 2106.05(a) through (c) and (e) through (h). Turning to those sections of the MPEP:
MPEP 2106.05(a) has to do with improvements to the functioning of a computer or to any other technology or technical field. The claims at issue do not improve the functioning of a computer or other technology. While the instant claims recite primers, their use for amplifying HLA genes HLA-G, HLA-E, and HLA-F, their inclusion in a detection reagent, their inclusion in a kit with a polymerase that is heat-resistant or strand displacing, optional 5’ functional moieties, the primers being DNA primers, and the primers in a buffer, power or lyophilized form, the claims do not improve upon amplification techniques or primer design. The claims merely use existing methods for these steps. Note that MPEP 2106.05(a) indicates that “[u]sing well-known standard laboratory techniques to detect enzyme levels in a bodily sample” is an example that the courts have indicated may not be sufficient to show an improvement to technology.
MPEP 2106.05(b) has to do with whether the claims involve the use of a particular machine. In this case, the claims do not involve the use of a particular machine. While the instant claims recite primers, their use for amplifying HLA genes HLA-G, HLA-E, and HLA-F, their inclusion in a detection reagent, their inclusion in a kit with a polymerase that is heat-resistant or strand displacing, optional 5’ functional moieties, the primers being DNA primers, and the primers in a buffer, power or lyophilized form, no such machines are required by the claim, and certainly no particular machines. Even if some conventional machine were recited in the claims, like a PCR machine, further considerations such as the particularity or generality of the recited machine must be taken into account, as well as whether the involvement of the machine is merely extra-solution activity. MPEP 2106.05(g) describes “extra-solution activity”, noting that “[d]etermining the level of a biomarker in blood” is an example of “mere data gathering” which the courts have found to be insignificant extra-solution activity.
MPEP 2106.05(c) has to do with whether the claims involve a particular transformation. Here, none of the limitations of the claims involve a particular transformation. For example, the existence of a primer does not transform that primer into something else. Furthermore, amplifying a gene does not transform that gene into something else.
MPEP 2106.05(e) has to do with “other meaningful limitations”. The additional limitations imposed upon the products of nature SEQ ID NOs 1-12 in the instant case have to do with their use for amplifying HLA genes HLA-G, HLA-E, and HLA-F, their inclusion in a detection reagent, their inclusion in a kit with a polymerase that is heat-resistant or strand displacing, optional 5’ functional moieties, the primers being DNA primers, and the primers in a buffer, power or lyophilized form. These limitations are not considered “meaningful limitations”. MPEP 2106.05(e) states: “The phrase "meaningful limitations" has been used by the courts even before Alice and Mayo in various contexts to describe additional elements that provide an inventive concept to the claim as a whole.” In addition, as has been discussed, they represent insignificant extra-solution activity, i.e. “data gathering”.
MPEP 2106.05(f) raises the question as to whether the additional elements recited in the claim represent “mere instructions to apply an exception”. Here, the judicial exception is the products of nature SEQ ID NOs 1-12. The additional elements recited in the claims (i.e. their use for amplifying HLA genes HLA-G, HLA-E, and HLA-F, their inclusion in a detection reagent, their inclusion in a kit with a polymerase that is heat-resistant or strand displacing, optional 5’ functional moieties, the primers being DNA primers, and the primers in a buffer, power or lyophilized form) does amount to mere instructions to apply the exception, since the use of the primers in amplification or their inclusion in another product serve as mere conventional uses and further applications of primers.
MPEP 2106.05(g) has to do with whether the additional elements of the claim amount to insignificant extra-solution activity. MPEP 2106.05(g) notes that “[d]etermining the level of a biomarker in blood” is an example of “mere data gathering” which the courts have found to be insignificant extra - solution activity. Likewise, MPEP 2106.05(g) notes that “[p]erforming clinical tests on individuals to obtain input for an equation” also represents insignificant extra-solution activity. This aligns closely with the instant claims, where the additional elements of the claims amount to amplifying genes and including the primers in other products.
MPEP 2106.05(h) has to do with whether the additional elements amount to more than generally linking the use of a judicial exception to a particular technological environment or field of use. Here, the recitation of the present invention relating to one or more kinds of HLA gene primers and the like is considered a “field of use”. However, as MPEP 2106.05(h) indications, such limiting to a particular “field of use” does not confer patentability on otherwise ineligible subject matter.
In addition, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception (as set forth in step 2B of the subject matter eligibility test; see MPEP 2106-III) because it was routine and conventional in the prior art to design DNA primers for HLA genes, use them for detecting HLA genes, include them in detection reagents and kits, and the primers being in a buffer, power or lyophilized form.
For example, Xu (CN110791558A; cited on the IDS filed April 4th, 2023, original document with English translation provided; previously cited) teaches one or more HLA gene primers selected from the group consisting of the following (1) to (3): (1) one or more kinds of HLA-G gene primers; (2) one or more kinds of HLA-E gene primers; and (3) one or more kinds-of HLA-F gene primers (Page 32, paragraph [0072]). Xu also teaches wherein the one or more HLA gene primers are HLA gene amplification primer sets selected from the group consisting of the following (1') to (3'): (1') an HLA-G gene amplification primer set including; (2') an HLA-E gene amplification primer set including; and (3') an HLA-F gene amplification primer set (Page 32, paragraph [0072]). Xu teaches a method for detecting an HLA gene, comprising: detecting one or more HLA genes in a sample obtained from a human subject using the one or more HLA gene primers (Page 11, paragraph [0011]: samples for invention come from humans; Page 32, paragraph [0072]), wherein the one or more HLA genes are selected from the group consisting of an HLA-G gene, an HLA-E gene, and an HLA-F gene (Page 32, paragraph [0072]). Xu teaches wherein the one or more HLA genes are detected by amplifying the one or more HLA genes (Page 32, paragraph [0072]). Xu teaches an HLA gene detection reagent comprising the one or more HLA gene primers (Page 32, paragraph [0072]). As evidenced by Godfrey (US20060068433A1; previously cited), a “detection reagent” (e.g. reagents for detection of nucleic acids) amounts to any of the reaction components of a PCR reaction, including primers, in the use case of PCR for detection (Page 11, paragraph [0112]). Xu teaches an HLA gene detection kit comprising: (a) one or more HLA gene primers (Page 30, paragraph [0067]). Xu teaches wherein primers are DNA primers (Pages 14-15, paragraphs [0015]-[0017]). Xu teaches wherein the polymerase is a heat-resistant polymerase (Page 41, paragraph [0086]). As evidenced by Takara Bio (FAQs: PCR Polymerases from Takara Bio [online]. Takara, [2013] [retrieved on June 4th, 2026]. Retrieved from: https://www.takarabio.com/documents/Frequently%20Asked%20Questions/PCRPolymerases_FAQ.pdf?srsltid=AfmBOor1Tx0UA5pL4k1XGTPM1j2tKhhqTUVYX9GDyGz1SSrJKiYVc2qW), PrimeSTAR polymerases are heat-resistant (Page 3, Denaturing conditions).
Godfrey (US20060068433A1; previously cited) teaches that a kit can include primers and a polymerase for detection of nucleic acids (Page 11, paragraph [0112]).
Dieffenbach (General concepts for PCR primer design, Genome Research, 1993, 3, S30-S37) teaches on primer design, including optimal primer length that may fall between 15 to 50 nucleotides (Page S31-S33, Primer Length).
Eshoo (US 20160186241 A1) teaches on containing a synthetic DNA oligonucleotide in a TE buffer (Page 1, paragraph [0005]).
Thirion (Lyophilized Matrix Containing Ready-to-Use Primers and Probe Solution for Standardization of Real-Time PCR and RT-qPCR Diagnostics in Virology, Viruses, January 2020, 12, 1-13) teaches on lyophilization of reaction reagents, including primers (Pages 1-2, Introduction).
Therefore, the additional elements beyond the natural products of primers do not represent an inventive concept since DNA primers for HLA, amplifying using HLA primers, including HLA primers and polymerase in a kit, and primers being in a buffer, power or lyophilized form was routine, well-known and conventional.
Having considered the factors discussed in MPEP 2106.04(c)(II) and MPEP 2106.05 (a)-(c) and (e)-(h), as well as the prior art of Xu and Godfrey, it is clear that the additional elements recited in the claims, whether considered individually or as a combination, do not integrate the judicial exception into a practical application of that exception in such a way as to provide meaningful limits on the use of the judicial exception. Therefore, claims 1-7 are rejected here under 35 U.S.C. 101.
Response to Arguments
Applicant's arguments filed March 30th, 2026 have been fully considered but they are not persuasive.
The Applicant first summarizes the Examiner’s previous rejection (Page 11 of the Remarks filed March 30th, 2026). The Applicant then states that “[p]rimer sets comprising two primers capable of amplifying a specific gene and methods using the primer sets are not found as laws of nature or natural phenomena” (Page 11 of the Remarks filed March 30th, 2026). The Applicant states that “ [t]he laws of nature or natural phenomena which can increase nucleic acids are as follows: (a) replication of genomic DNA (e.g., cell division); and (b) transcription of RNA strands (e.g., as an intermediate step in protein expression, or for RNA expression)”, followed by stating that these either do not use two specific primers or do not use a primer at all (Page 12 of the Remarks filed March 30th, 2026). The Applicant argues that primer sets comprising two primers capable of amplifying a specific gene and methods using the primer sets are not laws of nature or natural phenomena (Page 12 of the Remarks filed March 30th, 2026). The Applicant then cites aspects of the MPEP directed to abstract ideas and an example of primer sets not being directed to an abstract idea (Page 12 of the Remarks filed March 30th, 2026). The Applicant argues that given the current amended claim language, the Examiner’s allegations are improper (Page 13 of the Remarks filed March 30th, 2026). The Applicant gives reasoning such as the claimed primer sets not being functionally identical to the corresponding HLA gene sequence, that the primers have a specific length, and the primers are different from the HLA gene itself (Page 13 of the Remarks filed March 30th, 2026). The Applicant argues that primer sets are not merely a genetic structure because they comprise two specific genetic structures with particular lengths (Page 12 of the Remarks filed March 30th, 2026). The Applicant argues that there is support in the specification for the primers being markedly different from their naturally occurring counterpart, and that the primers are changed compared to nature (Pages 13-14 of the Remarks filed March 30th, 2026).
In response to these arguments, the Applicant is directed to MPEP 2106.04(c)(II)(C)(2), “[i]n Ambry Genetics, the court identified claimed DNA fragments known as "primers" as products of nature, because they lacked markedly different characteristics. University of Utah Research Foundation v. Ambry Genetics Corp., 774 F.3d 755, 113 USPQ2d 1241 (Fed. Cir. 2014). The claimed primers were single-stranded pieces of DNA, each of which corresponded to a naturally occurring double-stranded DNA sequence in or near the BRCA genes. The patentee argued that these primers had markedly different structural characteristics from the natural DNA, because the primers were synthetically created and because "single-stranded DNA cannot be found in the human body". The court disagreed, concluding that the primers’ structural characteristics were not markedly different than the corresponding strands of DNA in nature, because the primers and their counterparts had the same genetic structure and nucleotide sequence. 774 F.3d at 760, 113 USPQ2d at 1243-44. The patentee also argued that the primers had a different function than when they are part of the DNA strand because when isolated as a primer, a primer can be used as a starting material for a DNA polymerization process. The court disagreed, because this ability to serve as a starting material is innate to DNA itself, and was not created or altered by the patentee: In fact, the naturally occurring genetic sequences at issue here do not perform a significantly new function. Rather, the naturally occurring material is used to form the first step in a chain reaction--a function that is performed because the primer maintains the exact same nucleotide sequence as the relevant portion of the naturally occurring sequence. One of the primary functions of DNA’s structure in nature is that complementary nucleotide sequences bind to each other. It is this same function that is exploited here--the primer binds to its complementary nucleotide sequence. Thus, just as in nature, primers utilize the innate ability of DNA to bind to itself.
Ambry Genetics, 774 F.3d at 760-61, 113 USPQ2d at 1244. In sum, because the characteristics of the claimed primers were innate to naturally occurring DNA, they lacked markedly different characteristics from nature and were thus product of nature exceptions. A similar result was reached in Marden, where the court held a claim to ductile vanadium ineligible, because the "ductility or malleability of vanadium is . . . one of its inherent characteristics and not a characteristic given to it by virtue of a new combination with other materials or which characteristic is brought about by some chemical reaction or agency which changes its inherent characteristics". In re Marden, 47 F.2d 958, 959, 18 CCPA 1057, 1060, 8 USPQ 347, 349 (CCPA 1931).”
In summary, it has been held that primers corresponding to naturally occurring DNA lack markedly different characteristics, and therefore are considered products of nature, regardless of how long those primers may be, if they are in a primer set, or if they are functionally equivalent to the whole of a gene. As an example, it can be seen here that SEQ ID 1 aligns to the HLA-G gene in its entirely, with no other sequence included that would serve to distinguish it from the HLA-G gene itself.
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In addition, the use cases the Applicant cites ((a) replication of genomic DNA (e.g., cell division); and (b) transcription of RNA strands (e.g., as an intermediate step in protein expression, or for RNA expression)) cannot be found as situations to determine whether a claimed limitation is considered a product of nature or a natural phenomenon. The other aspects of the MPEP that the Applicant cites are directed to abstract ideas, which is not what the above rejection indicates as the judicial exception. Therefore, they cannot serve to overcome the rejection. As has already been indicated, the primers are considered a product of nature and the rest of the claimed limitations represent well-known and routine uses of primers.
Overall, the Applicant’s arguments are not found persuasive.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Modified - Necessitated by Amendment
Claims 2-4, 6, and 8-10 are rejected under 35 U.S.C. 103 as being unpatentable over Xu (CN110791558A; cited on the IDS filed April 4th, 2023, original document with English translation provided; previously cited), in view of GenBank (GenBank accession number NG_029039.1 [online]. GenBank, [2020] [retrieved on December 16th, 2025]. Retrieved from: https://www.ncbi.nlm.nih.gov/nuccore/334848115?sat=51&satkey=27463323; GenBank accession number BA000025.2 [online]. GenBank, [2016] [retrieved on December 17th, 2025]. Retrieved from: https://www.ncbi.nlm.nih.gov/nuccore/BA000025.2; GenBank accession number AB201549.1 [online]. GenBank, [2006] [retrieved on December 16th, 2025]. Retrieved from: https://www.ncbi.nlm.nih.gov/nuccore/AB201549.1; all previously cited) and Dieffenbach (General concepts for PCR primer design, Genome Research, 1993, 3, S30-S37).
Regarding instant claims 2 and 8-10, Xu teaches one or more HLA gene amplification primers sets which are selected from the group consisting of the following (1') to (3'): (1') an HLA-G gene amplification primer set; (2') an HLA-E gene amplification primer set; and (3') an HLA-F gene amplification primer set (Page 32, paragraph [0072]).
Xu does not teach wherein the one or more HLA gene primers are HLA gene amplification primer sets selected from the group consisting of the following specific SEQ ID NOs: (1') an HLA-G gene amplification primer set including (1a) a first primer comprising the nucleotide sequence of SEQ ID NO. 1 or the nucleotide sequence complementary thereto and (1b) a second primer comprising the nucleotide sequence of SEQ ID NO. 3 or the nucleotide sequence complementary thereto, wherein the first primer (1a) and the second primer (1b) each have a nucleotide length of 15 to 50; (2') an HLA-E gene amplification primer set including (2a) a first primer comprising the nucleotide sequence of SEQ ID NO. 5 or the nucleotide sequence complementary thereto and (2b) a second primer comprising the nucleotide sequence of SEQ ID NO. 7 or the nucleotide sequence complementary thereto, wherein the first primer (2a) and the second primer (2b) each have a nucleotide length of 15 to 50; and (3') an HLA-F gene amplification primer set including (3a) a first primer comprising the nucleotide sequence of SEQ ID NO. 9 or the nucleotide sequence complementary thereto and (3b) a second primer comprising the nucleotide sequence of SEQ ID NO. 11 or the nucleotide sequence complementary thereto, wherein the first primer (3a) and the second primer (3b) each have a nucleotide length of 15 to 50.
However, Xu teaches that all regions of an HLA gene may have important polymorphisms, including exons 1, 5, 6, 7, 5'-promoter, 3'-UTR, and intron regions (Pages 6 and 7, paragraph [0006]). Xu teaches that discovering new steps in understudied regions of HLA genes will provide detailed basic data for revealing the regulatory patterns of HLA expression (Page 7, paragraph [0006]). Xu teaches that because of the current lack of complete exon, intron, and especially 5'-promoter and 3'-UTR regulatory region sequences, it is difficult to conduct systematic full-length sequence polymorphism analysis of HLA-G, HLA-E, and HLA-F (Pages 9 and 10, paragraph [0008]). Therefore, Xu teaches on amplifying the full length of the HLA-G, HLA-E, and HLA-F genes with primers (Page 13, paragraph [0014]). Xu teaches that amplified regions of HLA-G, HLA-E, and HLA-F include the 5' promoter sequences, all exons, all introns, and the 3'-UTR sequences of the three genes (Page 13, paragraph [0014]). Finally, Xu teaches primers that hybridize to polymorphic bases are designed as degenerate bases to amplify all different sublineages of HLA-G, HLA-E, and HLA-F (Page 15, paragraph [0018]). This inherently indicates that all the primers are designed to amplify the full length of all different sublineages of HLA-G, HLA-E, and HLA-F, e.g. designed to hybridize with sequences conserved across many types of these HLA genes. When taking all of these teachings together, Xu teaches on gene primers of HLA genes that fall in the 5’ upstream and 3’ downstream region and hybridize to specific sequences conserved across HLA gene types and can further be used for full-length gene amplification. Therefore, it would be obvious to one of ordinary skill in the art to follow these teachings to design other primers for full-length HLA genes, and further use them for amplification. One of ordinary skill in the art would be motivated to do so for systematic full-length sequence polymorphism analysis of HLA-G, HLA-E, and HLA-F (Pages 9 and 10, paragraph [0008]).
GenBank, a resource for nucleotide sequences, teaches nucleotide sequences of the claimed genes which encompass the claimed SEQ IDs, as can be seen in the following alignments:
For the HLA-G gene, SEQ ID NOs: 1 and 3 were aligned to GenBank ascension number NG_029039.1, an entry for Homo sapiens HLA-G gene for major histocompatibility complex, class I, G, complete cds, allele: HLA-G*01:01:01:01. The SEQ IDs aligned with 100% identity.
SEQ ID NO: 1
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SEQ ID NO: 3
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Based on the full GenBank file and the alignments provided above, SEQ ID NO: 1 aligns in the 5’ upstream region and SEQ ID NO:3 aligns in the 3’ downstream region as the coding sequence of HLA-G starts at nucleotide 5001 and ends at nucleotide 9144 (NG_029039.1, Page 1, “gene” section for HLA-G gene). Finally, as evidenced by screenshots of several other GenBank entries for HLA-G, these primers align with many sublineages of HLA-G, meaning they are generally conserved sequences.
SEQ ID NO: 1
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SEQ ID NO: 3
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Therefore, given the teachings of Xu above, the primer sequences of SEQ ID NOs: 1 and 3 would be obvious. Using them in place of the primers taught by Xu would amount to simple substitution of one known element for another to yield predictable results as the primers follow the same general design as that of Xu, as discussed above (see MPEP 2141(III)).
For the HLA-E gene, SEQ ID NOs: 5 and 7 were aligned to GenBank ascension number BA000025.2, an entry for Homo sapiens genomic DNA, chromosome 6p21.3, HLA Class I region. The SEQ IDs aligned with 100% identity. It is noted by the Examiner that this sequence file is not specifically for HLA-E gene, but instead the HLA class I region of chromosome 6, which encompasses many of the HLA genes.
SEQ ID NO: 5
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SEQ ID NO: 7
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Based on the full GenBank file and the alignments provided above, SEQ ID NO: 5 aligns in the 5’ upstream region and SEQ ID NO: 7 aligns in the 3’ downstream region as the coding sequence of HLA-E starts at nucleotide 1447669 and ends at nucleotide 1452640 (BA000025.2, Page 45, “gene” section for HLA-E). Finally, as evidenced by screenshots of several other GenBank entries for HLA-E, these primers align with many sublineages of HLA-E, meaning they are generally conserved sequences.
SEQ ID NO: 5
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205
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209
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207
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It is noted by the Examiner that while the above sequence files are for the major histocompatibility complex genomic sequence at large, like the alignment of the SEQ ID NOs to BA000025.2, SEQ ID NO: 5 would hybridize 5’ upstream of the HLA-E gene in each sequence file.
SEQ ID NO: 7
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216
799
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212
809
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206
805
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Therefore, given the teachings of Xu above, the primer sequences of SEQ ID NOs: 5 and 7 would be obvious. Using them in place of the primers taught by Xu would amount to simple substitution of one known element for another to yield predictable results as the primers follow the same general design as that of Xu, as discussed above (see MPEP 2141(III)).
For the HLA-F gene, SEQ ID NOs: 9 and 11 were aligned to GenBank ascension number AB201549.1, an entry for Homo sapiens HLA-F gene for major histocompatibility complex, class I, F, complete cds. The SEQ IDs aligned with 100% identity.
SEQ ID NO: 9
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210
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SEQ ID NO: 11
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201
749
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Based on the full GenBank file and the alignments provided above, SEQ ID NO: 9 aligns in the 5’ upstream region and SEQ ID NO:11 aligns in the 3’ downstream region as the coding sequence of HLA-F starts at nucleotide 1388 and ends at nucleotide 4404 (AB201549.1, Page 1, “gene” section for HLA-F gene). Finally, as evidenced by screenshots of several other GenBank entries for HLA-F, these primers align with many sublineages of HLA-F, meaning they are generally conserved sequences.
SEQ ID NO: 9
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208
683
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209
678
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212
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SEQ ID NO: 11
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242
812
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207
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236
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Therefore, given the teachings of Xu above, the primer sequences of SEQ ID NOs: 9 and 11 would be obvious. Using them in place of the primers taught by Xu would amount to simple substitution of one known element for another to yield predictable results as the primers follow the same general design as that of Xu, as discussed above (see MPEP 2141(III)).
Neither of the references as currently cited teaches that the primers each have a nucleotide length of 15 to 50.
Dieffenbach, in a reasonably pertinent field, teaches on primer design, including optimal primer length that may fall between 15 to 50 nucleotides (Page S31-S33, Primer Length).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the primers of Xu, in view of GenBank, with the primer length of Dieffenbach. Since Dieffenbach teaches on primer design, which is reasonably pertinent to the primers of Xu, in view of GenBank, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because oligonucleotides between 18 and 24 bases tend to be very sequence specific of the annealing temperature of the PCR reaction is set within a few degrees of the primer melting temperature (Dieffenbach, Page S31, paragraph 3). Furthermore, longer oligonucleotides from 28-35 base long are useful when amplifying sequences where heterogeneity is expected (Dieffenbach, S31, paragraph 4).
Regarding claim 8-10, the sets of claim 2 are discussed above. Because the limitations of claims 8-10 are optional, the rejection of claim 2 also serves to reject the embodiments of claims 8-10 where the limitations are not required.
Regarding instant claim 3, Xu, in view of GenBank and Dieffenbach, teaches the one or more HLA gene primer sets according to claim 2. GenBank further teaches nucleotide sequences of the claimed genes which encompass the claimed SEQ ID NOs: 2, 4, 6, 8, 10, and 12, as seen in the following alignments to the same GenBank entries as those of the respective odd numbered SEQ IDs.
SEQ ID NO: 2 (comprising SEQ ID NO: 1 as claimed)
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SEQ ID NO: 4 (comprising SEQ ID NO: 3 as claimed)
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206
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SEQ ID NO: 6 (comprising SEQ ID NO: 5 as claimed)
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198
684
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SEQ ID NO: 8 (comprising SEQ ID NO: 7 as claimed)
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202
687
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SEQ ID NO: 10 (comprising SEQ ID NO: 9 as claimed)
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SEQ ID NO: 12 (comprising SEQ ID NO: 11 as claimed)
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As analyzed above for claim 2, each of these primers follows the primer design as taught by Xu (see 103 analysis for claim 2). Therefore, they would be obvious.
Regarding instant claim 4, Xu, in view of GenBank and Dieffenbach, teaches gene primers according to claim 1. Xu further teaches a method for detecting an HLA gene, comprising: amplifying one or more HLA genes in a sample obtained from a human subject using the one or more HLA gene primers to produce amplified nucleic acids (Page 11, paragraph [0011]: samples for invention come from humans; Page 32, paragraph [0072]), wherein the one or more HLA genes are selected from the group consisting of an HLA-G gene, an HLA-E gene, and an HLA-F gene (Page 32, paragraph [0072]). As analyzed in claim 2, the one or more HLA gene primer sets according to claim 2 are obvious.
Regarding instant claim 6, Xu teaches an HLA gene detection reagent comprising the one or more HLA gene primer sets according to claim 2 (Page 32, paragraph [0072]). As evidenced by Godfrey (US20060068433A1), a “detection reagent” (e.g. reagents for detection of nucleic acids) amounts to any of the reaction components of a PCR reaction, including primers, in the use case of PCR for detection (Page 11, paragraph [0112]). As analyzed in claim 2, the one or more HLA gene primer sets according to claim 2 are obvious.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Xu (CN110791558A; cited on the IDS filed April 4th, 2023, original document with English translation provided; previously cited), GenBank (GenBank accession number NG_029039.1 [online]. GenBank, [2020] [retrieved on December 16th, 2025]. Retrieved from: https://www.ncbi.nlm.nih.gov/nuccore/334848115?sat=51&satkey=27463323; GenBank accession number BA000025.2 [online]. GenBank, [2016] [retrieved on December 17th, 2025]. Retrieved from: https://www.ncbi.nlm.nih.gov/nuccore/BA000025.2; GenBank accession number AB201549.1 [online]. GenBank, [2006] [retrieved on December 16th, 2025]. Retrieved from: https://www.ncbi.nlm.nih.gov/nuccore/AB201549.1; all previously cited), and Dieffenbach (General concepts for PCR primer design, Genome Research, 1993, 3, S30-S37), as applied to claims 2-4 and 6, and further in view of Godfrey (US20060068433A1; previously cited).
Regarding instant claim 7, Xu, in view of GenBank and Dieffenbach, teaches gene primer sets according to claim 2. Xu further teaches an HLA gene detection kit comprising: (a) one or more HLA gene primer sets (Page 30, paragraph [0067]). As analyzed in claim 2, the one or more HLA gene primer sets according to claim 2 are obvious.
Xu teaches on a polymerase for use in their method (Page 41, paragraph [0086]). However, Xu does not teach that the kit includes a polymerase.
Godfrey, in the same field of endeavor, teaches that a kit can include a polymerase (Page 11, paragraph [0112]).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the kit of Xu with the polymerase of Godfrey. Since both Xu and Godfrey are in the same field of endeavor (e.g. kits with detection reagents), one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because, as stated in Godfrey, “In the commercialization of the methods described herein, certain kits for detection of specific nucleic acids will be particularly useful” (Page 11, paragraph [0112]).
Response to Arguments
Applicant's arguments filed March 30th, 2026 have been fully considered but they are not persuasive.
The Applicant first summarizes the Examiner’s previous rejection (Pages 14-15 of the Remarks filed March 30th, 2026). The Applicant disagrees, arguing first that Xu does not teach non-degenerate primers which can cover the full length of and can amplify the claimed HLA genes (Page 15 of the Remarks filed March 30th, 2026). The Applicant also argues that Xu cannot design primers which can cover the 3’ region of the claimed HLA genes (Page 15 of the Remarks filed March 30th, 2026). These arguments will be addressed below.
The Applicant provides the primers of Xu, along with alignments to the UCSC Genome Browser, arguing that Xu’s primers cannot cover the 3’ UTRs of the claimed HLA genes (Pages 15-17 of the Remarks filed March 30th, 2026). The Applicant argues that the claimed HLA gene amplification primer sets cover the full length of the claimed HLA genes and are superior to the primers of Xu (Page 17 of the Remarks filed March 30th, 2026).
In response to the Applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which the Applicant relies (i.e., covering 3’ UTRs) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). In addition, Xu provides a motivation for designing primers that cover the 3’ UTR given that the 3’ UTR regions contain regulatory sequences (see Pages 9-10, paragraph [0008] of Xu), reasonably suggesting that it would be obvious to design primers that account for this region of the claimed HLA genes.
The Applicant argues that Xu does not teach designing non-degenerate primers which can amplify various allele types of the claimed HLA genes (Page 17 of the Remarks filed March 30th, 2026). The Applicant cites the Examiner’s previous rejection, stating that Xu does not inherently indicate that non-degenerate primers are designed to hybridize with sequences conserved across many types of these HLA genes (Page 17 of the Remarks filed March 30th, 2026). The Applicant states that it is common knowledge that HLA genes have high sequence homology, and are highly rich in polymorphism (Page 17 of the Remarks filed March 30th, 2026). The Applicant states that primers designed to hybridize with sequences conserved across alleles of HLA genes tend to cross-react with other HLA genes (Page 18 of the Remarks filed March 30th, 2026). The Applicant argues that therefore, primers with high specificity to a specific HLA gene cannot be prepared by designing primers which can hybridize with sequences conserved across different sublineages of a specific HLA gene (Page 18 of the Remarks filed March 30th, 2026). The Applicant details common knowledge related to degenerate primers (Page 18 of the Remarks filed March 30th, 2026). The Applicant argues that given this knowledge, it is thought that Xu has decided that designing non-degenerate primers that can hybridize with conserved sequences in HLA genes is difficult (Page 18 of the Remarks filed March 30th, 2026). The Applicant states “it should be interpreted that Xu strongly indicates that all the primers are designed to hybridize to polymorphic bases as degenerate bases to amplify all different sublineages of HLA-G, HLA-E, and HLA-F (paragraph [0018]).” (Pages 18-19 of the Remarks filed March 30th, 2026). The Applicant states that Xu therefore does not teach designing non-degenerate primers which can amplify alleles of the claimed HLA genes (Page 19 of the Remarks filed March 30th, 2026).
In response to the Applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which the Applicant relies (i.e., non-degenerate primers, conserved sequences) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Furthermore, it is noted that the majority of the primers of Xu do not contain degenerate bases and are directed to specific HLA genes (see paragraphs [0015]-[0017] of Xu). It cannot be said that “Xu strongly indicates that all the primers are designed to hybridize to polymorphic bases as degenerate bases to amplify all different sublineages of HLA-G, HLA-E, and HLA-F” as has been argued given these teachings on non-degenerate primers. Xu therefore does provide teachings on primer design for non-degenerate primers for amplifying HLA genes. With respect to conserved sequences, as has already been noted, there is no claim limitation related to conserved sequences. Arguments related to design based on conserved sequences are not applicable given the lack of limitation related to design based on them. Finally, with regard to the argued common knowledge about degenerate primers, it is noted that no reference has been provided to indicate the presented common knowledge is actually commonly known in the art. Applicant is advised that MPEP 716.01(c) makes clear that “[t]he arguments of counsel cannot take the place of evidence in the record” (In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965)). Thus, Applicant should not merely rely upon counsel' s arguments in the place of evidence in the record.
The Applicant provides information related to the usefulness of the primer sets as claimed (Page 19 of the Remarks filed March 30th, 2026). The Applicant argues that this usefulness is not obvious from Xu in view of the GenBank entries (Page 19 of the Remarks filed March 30th, 2026). The Applicant argues it was unpredictable prior to their invention whether non-degenerate primer sets possessing their useful features could be provided, and therefore the rejection constitutes impermissible hindsight (Page 19 of the Remarks filed March 30th, 2026). The Applicant argues that it is only natural that the claimed primers would exhibit 100% identity to the GenBank entries because they are designed to be highly adapted to a wide variety of polymorphisms, and therefore alignments are not appropriate grounds for obviousness (Pages 19-20 of the Remarks filed March 30th, 2026).
In response to these arguments, it is noted that arguments related to non-degenerate primers have been addressed above. In response to the Applicant's argument that the references fail to show certain features of the invention related to obviousness of the primer sets as taught by Xu, in view of GenBank, it is noted that the features upon which applicant relies (i.e., cover full length of HLA genes and amplifying various allele types in African, Japanese, and Hispanic American populations) are not recited in the rejected claims. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Furthermore, in response to the Applicant's argument that the Examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). Furthermore, aligning the claimed sequences is indeed an appropriate ground for obviousness when the alignment shows the primers follow the design characteristics taught by Xu, and also that they align to the intended target HLA gene, thus obviating that the sequence would amplify as claimed.
The Applicant argues that primer design that considers only conserved sequences is insufficient for designing primers to target a specific gene and provides art references related to this argument (Pages 20-21 of the Remarks filed March 30th, 2026). The Applicant argues that, given these cases indicate that in silico primer design which considers only sequences conserved in a specific HLA gene which is highly polymorphic is insufficient for designing primers targeting the specific gene (Page 21 of the Remarks filed March 30th, 2026).
In response to this argument, it is noted that neither of the cited references are related to the rejection as presented. Furthermore, they are related to features that are not claimed (e.g. designing based on conserved sequences) as noted above.
The Applicant restates the usefulness of the claimed primer sets and argues that this usefulness is not obvious from Xu in view of GenBank (Page 21 of the Remarks filed March 30th, 2026).
In response to this statement, the Applicant is referred to the arguments above regarding the obviousness of the primer sets given Xu and GenBank.
Overall, the Applicant’s arguments are not found persuasive.
New - Necessitated by Amendment
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Xu (CN110791558A; cited on the IDS filed April 4th, 2023, original document with English translation provided; previously cited), in view of GenBank (GenBank accession number NG_029039.1 [online]. GenBank, [2020] [retrieved on December 16th, 2025]. Retrieved from: https://www.ncbi.nlm.nih.gov/nuccore/334848115?sat=51&satkey=27463323; GenBank accession number BA000025.2 [online]. GenBank, [2016] [retrieved on December 17th, 2025]. Retrieved from: https://www.ncbi.nlm.nih.gov/nuccore/BA000025.2; GenBank accession number AB201549.1 [online]. GenBank, [2006] [retrieved on December 16th, 2025]. Retrieved from: https://www.ncbi.nlm.nih.gov/nuccore/AB201549.1; all previously cited) and Dieffenbach (General concepts for PCR primer design, Genome Research, 1993, 3, S30-S37), as applied to claims 2-4, 6, and 8-10 and further analyzed below.
Regarding instant claim 11, Xu, in view of GenBank and Dieffenbach, teaches the one or more HLA gene amplification primer sets according to claim 2. Xu and GenBank in combination teach wherein the first primers (1a), (2a) and (3a), and the second primers (1b), (2b) and (3b) are each a DNA primer (Xu, Pages 14-15, paragraphs [0015]-[0017] for DNA primers, see GenBank screenshots in claim 2 for DNA alignments).
Claims 14 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Xu (CN110791558A; cited on the IDS filed April 4th, 2023, original document with English translation provided; previously cited), GenBank (GenBank accession number NG_029039.1 [online]. GenBank, [2020] [retrieved on December 16th, 2025]. Retrieved from: https://www.ncbi.nlm.nih.gov/nuccore/334848115?sat=51&satkey=27463323; GenBank accession number BA000025.2 [online]. GenBank, [2016] [retrieved on December 17th, 2025]. Retrieved from: https://www.ncbi.nlm.nih.gov/nuccore/BA000025.2; GenBank accession number AB201549.1 [online]. GenBank, [2006] [retrieved on December 16th, 2025]. Retrieved from: https://www.ncbi.nlm.nih.gov/nuccore/AB201549.1; all previously cited) and Dieffenbach (General concepts for PCR primer design, Genome Research, 1993, 3, S30-S37), as applied to claims 2-4 and 6, and further in view of Eshoo (US 20160186241 A1).
Regarding instant claims 14 and 16, Xu, in view of GenBank and Dieffenbach, teaches the HLA gene detection reagent according to claim 6.
None of these references teach wherein the first primers (1a), (2a) and (3a), and the second primers (1b), (2b) and (3b) are each contained in a form of a powder or a buffer (claim 14 and 16). They also do not teach wherein the buffer is selected from the group consisting of a TE (Tris-EDTA) buffer, a hydrochloric acid-potassium chloride buffer, a glycine-hydrochloric acid buffer, a citrate buffer, an acetate buffer, a citrate-phosphate buffer, a phosphate buffer, a Tris-hydrochloric acid buffer, a glycine-sodium hydroxide buffer, a carbonate-bicarbonate buffer, a borate buffer, and a tartrate buffer (claim 16).
Eshoo, in a reasonably pertinent field, teaches on containing a synthetic DNA oligonucleotide in a TE buffer (Page 1, paragraph [0005]).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the detection reagent of Xu, in view of GenBank and Dieffenbach, with the buffer of Eshoo. Since teaches on buffers to contain nucleic acids, which is reasonably pertinent to the detection reagent of Xi, in view of GenBank and Dieffenbach, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because buffers find particular use for the stabilization of trace amounts of nucleic acid molecules in a variety of environments, including repeated freeze/thaw cycles (Eshoo, Page 1, paragraph [0004]).
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Xu (CN110791558A; cited on the IDS filed April 4th, 2023, original document with English translation provided; previously cited), GenBank (GenBank accession number NG_029039.1 [online]. GenBank, [2020] [retrieved on December 16th, 2025]. Retrieved from: https://www.ncbi.nlm.nih.gov/nuccore/334848115?sat=51&satkey=27463323; GenBank accession number BA000025.2 [online]. GenBank, [2016] [retrieved on December 17th, 2025]. Retrieved from: https://www.ncbi.nlm.nih.gov/nuccore/BA000025.2; GenBank accession number AB201549.1 [online]. GenBank, [2006] [retrieved on December 16th, 2025]. Retrieved from: https://www.ncbi.nlm.nih.gov/nuccore/AB201549.1; previously cited) and Dieffenbach (General concepts for PCR primer design, Genome Research, 1993, 3, S30-S37), as applied to claims 2-4 and 6, and further in view of Thirion (Lyophilized Matrix Containing Ready-to-Use Primers and Probe Solution for Standardization of Real-Time PCR and RT-qPCR Diagnostics in Virology, Viruses, January 2020, 12, 1-13).
Regarding instant claim 15, Xu, in view of GenBank and Dieffenbach teaches the HLA gene detection reagent according to claim 6.
None of these references teach wherein the first primers (1a), (2a) and (3a), and the second primers (1b), (2b) and (3b) are contained in a form of a lyophilized powder.
Thirion, in a reasonably pertinent field, teaches on lyophilization of reaction reagents, including primers (Pages 1-2, Introduction).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the detection reagent of Xu, in view of GenBank and Dieffenbach, with the lyophilized powder of Thirion. Since Thirion teaches on diagnostic procedures involving primers, which is reasonably pertinent to the detection reagent of Xi, in view of GenBank and Dieffenbach, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because lyophilized reagents are more stable than liquid formulations (Thirion, Page 2, paragraph 1).
Claims 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Xu (CN110791558A; cited on the IDS filed April 4th, 2023, original document with English translation provided; previously cited), GenBank (GenBank accession number NG_029039.1 [online]. GenBank, [2020] [retrieved on December 16th, 2025]. Retrieved from: https://www.ncbi.nlm.nih.gov/nuccore/334848115?sat=51&satkey=27463323; GenBank accession number BA000025.2 [online]. GenBank, [2016] [retrieved on December 17th, 2025]. Retrieved from: https://www.ncbi.nlm.nih.gov/nuccore/BA000025.2; GenBank accession number AB201549.1 [online]. GenBank, [2006] [retrieved on December 16th, 2025]. Retrieved from: https://www.ncbi.nlm.nih.gov/nuccore/AB201549.1; all previously cited), Dieffenbach (General concepts for PCR primer design, Genome Research, 1993, 3, S30-S37), and Godfrey (US20060068433A1; previously cited), as applied to claim 7, and further in view of Takara Bio (FAQs: PCR Polymerases from Takara Bio [online]. Takara, [2013] [retrieved on June 4th, 2026]. Retrieved from: https://www.takarabio.com/documents/Frequently%20Asked%20Questions/PCRPolymerases_FAQ.pdf?srsltid=AfmBOor1Tx0UA5pL4k1XGTPM1j2tKhhqTUVYX9GDyGz1SSrJKiYVc2qW).
Regarding instant claim 17, Xu, in view of GenBank, Dieffenbach, and Godfrey, teaches the HLA gene detection kit according to claim 7. Xu further teaches wherein the polymerase is a Takara PrimeSTAR GXL DNA polymerase (Page 41, paragraph [0086]). As evidenced by Takara Bio, PrimeSTAR polymerases are heat-resistant (Page 3, Denaturing conditions).
Conclusion
All claims stand rejected.
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 Allison E Schloop whose telephone number is (703)756-4597. The examiner can normally be reached Monday-Friday 8:30-5 ET.
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/ALLISON E SCHLOOP/Examiner, Art Unit 1683
/Robert T. Crow/Primary Examiner, Art Unit 1683
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