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 statements (IDSs) submitted on April 4th, 2025 and May 13th, 2025 are acknowledged. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Summary
Claims 1-7 have been amended. Claims 1-7 are pending. Claims 1-7 are under examination and discussed in this Office action.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see paragraph [0046] of the instant specification). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Rejections - 35 USC § 112(b)
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 4 and 5 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 4 recites the limitation “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 according to claim 1, wherein the one or more kinds of HLA genes are selected from the group consisting of an HLA-G gene, an HLA-E gene, and an HLA-F gene.” Based on this recitation, there is an option of using one gene primer on its respective HLA gene target for detection. Given this interpretation, however, it is unclear how one gene primer may be used for the detection of a gene when it appears the intended method of detection is PCR amplification based on claim 5 and the description and examples provided in the specification. It would be known by one of ordinary skill in the art that two gene primers are generally required for PCR amplification. It is also expressly stated in the specification that for PCR, the number of primers required for gene amplification is 2 (paragraph [0023]). Therefore, it is unclear how one primer is intended to accomplish detection as claimed. Claim 5 is also rejected here for its dependence on claim 4 and not further clarifying the identified issue. For the purpose of compact prosecution, claims 4 and 5 will be interpreted to depend from claim 2, which specifically claims amplification primer sets.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-7 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 detecting HLA genes HLA-G, HLA-E, and HLA-F, their inclusion in a detection reagent, and their inclusion in a kit with a polymerase, 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 detecting HLA genes HLA-G, HLA-E, and HLA-F, their inclusion in a detection reagent, and their inclusion in a kit with a polymerase, 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 detecting HLA genes HLA-G, HLA-E, and HLA-F, their inclusion in a detection reagent, and their inclusion in a kit with a polymerase. 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 detecting HLA genes HLA-G, HLA-E, and HLA-F, their inclusion in a detection reagent, and their inclusion in a kit with a polymerase) 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 primers for HLA genes, use them for detecting HLA genes, and include them in detection reagents and kits.
For example, Xu (CN110791558A; cited on the IDS filed April 4th, 2023, original document with English translation provided) 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), 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]).
Godfrey (US20060068433A1) teaches that a kit can include primers and a polymerase for detection of nucleic acids (Page 11, paragraph [0112]).
Therefore, the additional elements beyond the natural products of primers do not represent an inventive concept since primers for HLA, amplifying using HLA primers, and including HLA primers and polymerase in a kit 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.
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.
Claims 1-6 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), 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).
Regarding instant claim 1 and 2, Xu 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; (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 that the one or more gene primers for each HLA gene are specifically the SEQ ID NOs as follows: (1) one or more HLA-G gene primers which are (1a) a first primer comprising the nucleotide sequence of SEQ ID NO. 1 or the nucleotide sequence complementary thereto and/or (1b) a second primer comprising the nucleotide sequence of SEQ ID NO. 3 or the nucleotide sequence complementary thereto; (2) one or more HLA-E gene primers which are (2a) a first primer comprising the nucleotide sequence of SEQ ID NO. 5 or the nucleotide sequence complementary thereto and/or (2b) a second primer comprising the nucleotide sequence of SEQ ID NO. 7 or the nucleotide sequence complementary thereto; and (3) one or more HLA-F gene primers which are (3a) a first primer comprising the nucleotide sequence of SEQ ID NO. 9 or the nucleotide sequence complementary thereto and/or (3b) a second primer comprising the nucleotide sequence of SEQ ID NO. 11 or the nucleotide sequence complementary thereto. Xu also 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; (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; 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.
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
PNG
media_image1.png
212
846
media_image1.png
Greyscale
SEQ ID NO: 3
PNG
media_image2.png
203
841
media_image2.png
Greyscale
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
PNG
media_image3.png
253
694
media_image3.png
Greyscale
PNG
media_image4.png
230
678
media_image4.png
Greyscale
PNG
media_image5.png
211
684
media_image5.png
Greyscale
SEQ ID NO: 3
PNG
media_image6.png
216
696
media_image6.png
Greyscale
PNG
media_image7.png
219
682
media_image7.png
Greyscale
PNG
media_image8.png
213
677
media_image8.png
Greyscale
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
PNG
media_image9.png
206
688
media_image9.png
Greyscale
SEQ ID NO: 7
PNG
media_image10.png
206
684
media_image10.png
Greyscale
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
PNG
media_image11.png
205
768
media_image11.png
Greyscale
PNG
media_image12.png
209
737
media_image12.png
Greyscale
PNG
media_image13.png
207
741
media_image13.png
Greyscale
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
PNG
media_image14.png
216
799
media_image14.png
Greyscale
PNG
media_image15.png
212
809
media_image15.png
Greyscale
PNG
media_image16.png
206
805
media_image16.png
Greyscale
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
PNG
media_image17.png
210
744
media_image17.png
Greyscale
SEQ ID NO: 11
PNG
media_image18.png
201
749
media_image18.png
Greyscale
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
PNG
media_image19.png
208
683
media_image19.png
Greyscale
PNG
media_image20.png
209
678
media_image20.png
Greyscale
PNG
media_image21.png
212
685
media_image21.png
Greyscale
SEQ ID NO: 11
PNG
media_image22.png
242
812
media_image22.png
Greyscale
PNG
media_image23.png
207
895
media_image23.png
Greyscale
PNG
media_image24.png
236
897
media_image24.png
Greyscale
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)).
Regarding instant claim 3, Xu, in view of GenBank, teaches the one or more HLA gene primers according to claim 1. 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)
PNG
media_image25.png
212
835
media_image25.png
Greyscale
SEQ ID NO: 4 (comprising SEQ ID NO: 3 as claimed)
PNG
media_image26.png
206
843
media_image26.png
Greyscale
SEQ ID NO: 6 (comprising SEQ ID NO: 5 as claimed)
PNG
media_image27.png
198
684
media_image27.png
Greyscale
SEQ ID NO: 8 (comprising SEQ ID NO: 7 as claimed)
PNG
media_image28.png
202
687
media_image28.png
Greyscale
SEQ ID NO: 10 (comprising SEQ ID NO: 9 as claimed)
PNG
media_image29.png
204
741
media_image29.png
Greyscale
SEQ ID NO: 12 (comprising SEQ ID NO: 11 as claimed)
PNG
media_image30.png
205
751
media_image30.png
Greyscale
As analyzed above for claim 1, each of these primers follows the primer design as taught by Xu (see 103 analysis for claim 1). Therefore, they would be obvious.
Regarding instant claim 4, Xu, in view of GenBank, teaches gene primers according to claim 1. Xu further 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]). As analyzed in claim 1, the one or more HLA gene primers according to claim 1 are obvious.
Regarding instant claim 5, Xu, in view of GenBank, teaches the method according to claim 4. Xu further teaches wherein the one or more HLA genes are detected by amplifying the one or more HLA genes (Page 32, paragraph [0072]).
Regarding instant claim 6, Xu teaches an HLA gene detection reagent comprising the one or more HLA gene primers according to claim 1 (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 1, the one or more HLA gene primers according to claim 1 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) and 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), as applied to claims 1-6, and further in view of Godfrey (US20060068433A1).
Regarding instant claim 7, Xu, in view of GenBank, teaches gene primers according to claim 1. Xu further teaches an HLA gene detection kit comprising: (a) one or more HLA gene primers (Page 30, paragraph [0067]). As analyzed in claim 1, the one or more HLA gene primers according to claim 1 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]).
Conclusion
All claims are rejected.
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.
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, Anne Gussow can be reached at (571) 272-6047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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.
/ALLISON E SCHLOOP/Examiner, Art Unit 1683
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683