DETAILED ACTION
The present Office Action is responsive to the Amendment received on July 21, 2026.
Preliminary Remark
Claims 4-9 and 26 are canceled.
Claims 21-25 and 27-31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on October 29, 2025.
Information Disclosure Statement
The IDS received on April 29, 2026 is proper and is being considered by the Examiner. The IDS was received with the statement under 1.97(e)(1).
Drawings
The objection made to the specification for containing an embedded hyperlink and/or browser-executable code, made in the Office Action mailed on April 21, 2026 is withdrawn in view of the Amendment received on July 21, 2026.
Claim Rejections - 35 USC § 112
The rejection of claims 1-20 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particularly point out and distinctly claim the subject matter, made in the Office Action mailed on April 21, 2026 is withdrawn in view of the Amendment received on July 21, 2026.
The rejection of claims 1, 14, 15, and 20 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement, made in the Office Action mailed on April 21, 2026 is withdrawn in view of the Amendment received on July 21, 2026.
Rejection – New Grounds, Necessitated by Amendment
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 2 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 2 depends from claim 1. Claim 1 recites that the kit comprises a probe set that comprises at least one probe for each of the genes recited therein. Claim 2 recites only a subset of the genes recited in parent claim 1, improperly broadening the breadth established by claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 101
The rejection of claims 4-9 under 35 U.S.C. 101 because the claimed invention is directed to the judicial exception of naturally occurring phenomenon without significantly more, made in the Office Action mailed on April 21, 2026 is withdrawn in view of the Amendment received on July 21, canceling the rejected claims.
Rejection, Maintained
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.
The rejection of claims 1-3 and 10-20 under 35 U.S.C. 101 because the claimed invention is directed to the judicial exception of naturally occurring phenomenon without significantly more, made in the Office Action mailed on April 21, 2026 is maintained for the reasons of record.
Applicants’ clam amendment and arguments presented in the Amendment received on July 21, 2026 have been carefully considered but they have not been found persuasive for the reasons discussed in the, “Response to Arguments’ section.
The Rejection:
The claims recite a set of nucleic acid sequences whose base sequences are found in nature. This judicial exception is not integrated into a practical application because the claims generically recite a probe set that is capable of detecting the expression of naturally occurring sequences, thus embracing nucleic acid sequences that exist in nature.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception based on the analysis under the current Patent Eligibility Guidelines (herein, “PEG”) as discussed below.
Step 1 Inquiry under PEG
Step 1 inquiry under Patent Eligibility Guidelines (herein, “PEG”) determines whether or not the claimed invention is drawn to one of the recognized statutory classes of invention. Claims 1-20 satisfy the present inquiry as being drawn to a product.
Step 2A Inquiry under PEG
A recently revised PEG now performs step 2A inquiry under a 2-prong analysis, and the subject claims analyzed accordingly as follows:
Prong 1:
Prong-1 inquiry under step 2A determines whether the claim(s) recites an abstract idea, a law of nature, or a natural phenomenon. As stated above, claims are directed to a kit comprising a probe set, and the probe set is recited generically and embrace nucleotide base sequences which are found in nature (either by reciting their “target” (or marker sequence), or by way of the SEQ ID Numbers).
Prong 2:
Prong-2 inquiry under step 2A determines whether or not the claims recite additional elements that integrate the judicial exception into a practical application in a manner that imposes a meaningful limit on the judicial exception.
Claims 1-19 do not recite any additional features. The probe set is defined by the marker they are capable of detecting, which continue to embrace the nucleotide sequence that exist in nature (found as portion of a naturally existing sequence), or by specific sequences (by SEQ ID Numbers), which nevertheless do the same.
Claim 20 recite an additional feature of the kit comprising a ligase. However, a ligase is also a naturally existing product and the recitation of two naturally existing elements (i.e., combination of judicial exceptions) do not together render the claimed product patent eligible.
The fact that the probe set can be used for an identified usage does not make the probe set patent eligible as the set embraces a judicial exception and a combination of an additional element (i.e., ligase) whic is an additional judicial exception fails to add more.
As explained by the Supreme Court, in order to transform a judicial exception into a patent-eligible application, the additional element or combination of elements must do ‘more than simply stat[e] the [judicial exception] while adding the words ‘apply it’”. Alice Corp. v. CLS Bank, 573 U.S. __, 134 S. Ct. 2347, 2357, 110 USPQ2d 1976, 1982-83 (2014) (quoting Mayo Collaborative Servs. V. Prometheus Labs., Inc., 566 U.S. 66, 72, 101 USPQ2d 1961, 1965). Thus, for example, claims that amount to nothing more than an instruction to apply the abstract idea using a generic computer do not render an abstract idea eligible. Alice Corp., 134 S. Ct. at 2358, 110 USPQ2d at 1983. See also 134 S. Ct. at 2389, 110 USPQ2d at 1984 (warning against a § 101 analysis that turns on “the draftsman’s art”) (MPEP 2106.05(f))
Step 2B Inquiry under PEG
Step 2B inquiry of the PEG determines whether or not additional elements are provided and whether such elements amount to significantly more than the judicial exception in the claims.
Presently, the additional elements which are provided in the claims that recite that the judicial exceptions are claimed as kit and the inclusion of a ligase fail to further add more than the judicial exception because inclusion of another judicial exception such as a ligase does not specifically limit the presently recited judicial exception as they are widely applicable and routinely included in diagnostic kits in the field of molecular diagnostics.
Therefore, these elements are not deemed significantly more than inclusion of that are commonly used, routine and conventional.
Therefore, the present claims lack patent eligibility.
Response to Arguments:
Applicants traverse the rejection.
Applicants state that claim 1, as amended is directed to a gene expression assay kit comprising a specifically defined set of probes and therefore does not merely recite a naturally occurring nucleic acid sequence as such (page 22, Response).
Applicants state that a manufactured assay kit comprising probes selected and assembled to detect the RNA expression of a particular combination of 35 markers, including 24 tumor-cell markers and 11 markers associated with bystander non-tumor cells of the lymphoma microenvironment is not a naturally occurring composition (page 22, Response).
Further, Applicants contend that the claimed probes are not naturally occurring RNA or DNA molecules isolated from a patient sample. Rather, as disclosed in the specification, the probes may be DNA or RNA or a combination of DNA and RNA and may be single stranded or double-stranded or part-single stranded and part double-stranded and may include short hairpin (shRNA) and therefore, are not directed to a naturally occurring product or natural phenomenon (page 22, Response).
These arguments have been carefully considered but have not been found persuasive.
Preliminarily, Applicants’ contention that probes may be DNA/RNA or combination of DNA or RNA, part hairpin, double-stranded or single-stranded are not deemed persuasive because the claims do not actively require that the probe comprise such a configuration.
Rather, claims simply recite that the probe set comprises at least one probe for detecting RNA expression of each of the 35 recited genes. There simply is no requirement that the sequence is double-, single-, partially-double-, or hairpin in configuration.
As Applicants are well-aware, 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).
As to the claimed combination of probes being “curated,” for the determination of 35 RNA markers, this argument is not found persuasive because the claims nevertheless embrace sequence portions that are found in the naturally existing DNA and/or RNA.
Such an issue was already settled in Ambry (citation omitted), wherein claims drawn to a primer pair was, which are single-stranded, deemed patent ineligible although they are specially configured to amplify a relevant portion on BRCA gene for BRCA mutation analysis.
In Ambry, the court did not consider whether the genomic DNA of BRCA could be utilized as a primer because it contained all of the primer sequences being claimed. Rather, the issue was in whether or not the claims were “claiming” a portion of a naturally existing gene sequence.
Expounding, in Ambry, one of the patents under suit was U.S. Patent 5,747,282, with specific claims 16 and 17:
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Claims 16 and 17 of the ‘282 patent are drawn to a pair of primers (see reproduced claim 16):
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And upon consideration of these pair of primers, the court stated the below:
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Inferring from this, the functionality of the primers by recitation of their present intended usage (i.e., configured to amplify a whole genome or whole transcriptome) does not render the claimed subject matter patent-eligible, in much the same way the functionality of the primer pairs in Ambry decision did not render them patent-eligible.
This is because the primer pairs of the '282 patent (from Ambry) had their own specific functionality. They were single-stranded. They were in a pair, able to amplify a specific portion of the human genome (i.e., BRCA gene or a portion thereof).
While a pair of primers had not existed in their physically distinct forms (i.e., two separate single-stranded nucleic acids), which together performed a function of amplifying a specific portion of a human genome, the court found that the primer pairs did not satisfy the patent eligible requirement under 35 U.S.C.
This rationale is similarly extended to the claimed set of probes, which is collection of oligonucleotides, whose sequences are “identical sequence” of the recited genes found in nature, thus failing to satisfy the eligibility requirement under 101 analysis.
While much can be made of the claim reciting the judicial exception being comprised in a “kit,” the recitation of the kit does not add meaningfully apply more than the judicial exception itself.
Therefore, the claims are not deemed patent eligible.
Claim Rejections - 35 USC § 102
The rejection of claims 4-9 under 35 U.S.C. 102(a)(1) as being anticipated by GeneChip® U133 Arrays (published 2007, pages 1-8, retrieved on-line from https://www.cancer.gov/ccg/research/structural-genomics/tcga/using-tcga-data/technology/affymetrix-u133-data-sheet, herein, “U133”), made in the Office Action mailed on April 21, 2026 is withdrawn in view of the Amendment received on July 21, canceling the rejected claims.
Rejection, Maintained
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
The rejection of claims 1-3 and 10-14 under 35 U.S.C. 102(a)(1) as being anticipated by GeneChip® U133 Arrays (published 2007, pages 1-8, retrieved on-line from https://www.cancer.gov/ccg/research/structural-genomics/tcga/using-tcga-data/technology/affymetrix-u133-data-sheet, herein, “U133”), made in the Office Action mailed on April 21, 2026 is maintained for the reasons of record.
Applicants’ claim amendment and arguments presented in the Amendment received on July 21, 2026 have been carefully considered but they have not been found persuasive for the reasons discussed in the, “Response to Arguments” section.
The Rejection:
U133 teaches arrays of probe sequences on arrays (U133 Plus 2.0) comprising every human expressed gene (“GeneChip® Human Genome U133 Plus 2.0 Array (single array, cartridge format) – Analyze gene expression across entire human genome for one sample”), page 1, 1st column).
Because U133 teaches a kit (see Figure 1) comprising an array comprising a set of probes that are target an entire human genome, the array would necessarily comprise probes targeting the recited markers. Because a product is defined strictly by its physical element, absent the intended usage resulting in a physical distinction, the product is anticipated.
Therefore, U133 anticipates the invention as claimed.
Response to Arguments:
Applicants traverse the rejection.
Applicants contend that GeneChip U133 does not disclose or expressly or inherently, a gene expression assay kit comprising the particular combination of probes now recited in claim 1, nor does GeneChip U133 disclose a probe set selected to distinguish among the seven recited B-cell non-Hodgkin Lymphoma subtypes: ABC DLBCL, GCBDLBCL, PMBL, FL, MCL, SLL, and MZL because a generalized genome-wide expression-profiling platform is not a clear and unequivocal disclosure of the specifically claimed probe set arranged as such (page 23-24, Response).
This argument has been carefully considered but has not been found persuasive.
Applicants are reminded that the claimed kit comprises a probe set which comprises a collection of probes that detect the expression of the recited genes, which allows the inclusion of other elements, such as other probes.
Because Affymetrix gene chip contains probes set of the human expressed genes, the chip would necessarily comprise probes which detect the expression levels of the recited genes, as well as additional genes. As to the capability of this gene chip in its ability to distinguish among the sever recited B-cell non-Hodkin Lymphoma subtypes, the Office contends that the chip is indeed capable of providing that information as the chip will necessarily provide the expression levels of those 35 genes, which can be interpreted by the practitioner. In other words, the ability of the chip to provide the information is largely based on the user of the product, and not necessarily the product itself.
Because a user can utilize GeneChip U133 to determine the expression levels of the recited genes, this chip is fully able to provide the necessary information.
Therefore, the invention as claimed is anticipated by GeneChip U133.
Claim Rejections - 35 USC § 103
The rejection of claims 1, 4, 14, 15, and 20 under 35 U.S.C. 103 as being unpatentable over Zekri et al. (Asian Pacific Journal of Cancer Prevention, 2013, vol. 14, pages 4393-4398) in view of in view of Yusenko et al. (BMC Cancer, May 2009, vol. 9, no. 152, pages 1-10), made in the Office Action mailed on April 21, 2026 is withdrawn in view of the Amendment received on July 21, 2026.
Rejection – Maintained
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 rejection of claim 20 under 35 U.S.C. 103 as being unpatentable over GeneChip® U133 Arrays (published 2007, pages 1-8, retrieved on-line from https://www.cancer.gov/ccg/research/structural-genomics/tcga/using-tcga-data/technology/affymetrix-u133-data-sheet, herein, “U133”) in view of Yusenko et al. (BMC Cancer, May 2009, vol. 9, no. 152, pages 1-10) made in the Office Action mailed on April 21, 2026 is maintained for the reasons of record.
Applicants’ claim amendment and arguments presented in the Amendment received on July 21, 2026 have been carefully considered but they have not been found persuasive for the reasons discussed in the, “Response to Arguments” section.
The Rejection:
The teachings of U133 have already been discussed above.
U133 does not teach a kit further comprising a ligase.
Yusenko et al. teach that ligase is conventionally used in a molecular diagnostics assay such ligating an adapter (“250 ng of genomic DNA was digested with NspI and then ligated to and adaptor with T4 ligase”, page 3, 1st column).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of U133 with the conventional knowledge available to one of ordinary skill in the art in the field of molecular diagnostics, such as those taught by Yusenko et al., for the various purposes of utilizing ligases when preparing nucleic acids for detection.
A kit of multiple reagents of a kit, although packaged together, need not necessarily be used together in a single method. Because ligases are employed in may applications such as labeling, ligation of adapters, packaging them together with the array of U133 would have benefited said one of ordinary skill in the art for purposes not necessarily limited to the use of the array.
Therefore, the invention as claimed is deemed prima facie obvious over the cited references.
Response to Arguments:
Applicants traverse the rejection.
Applicants’ arguments rely on their arguments presented for the anticipation rejection above, which have been fond unpersuasive and already addressed above.
The usage of ligase and the addition of such a reagent need not be the same as that of Applicants.
This is clear from the rational discussed above for packaging a ligase into a kit for independent reasons unrelated to Applicants’ intent, such as labeling, or ligation of adapters, etc., the Office maintains the inclusion of a ligase into a kit would have been obvious.
“The Circuit first erred in holding that courts and patent examiners should look only to the problem the patentee was trying to solve. Under the correct analysis, any need or problem known in the field and addressed by the patent can provide a reason for combining the elements in the manner claimed.” (page 6, Opinion, KSR)
“The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006)
Therefore, the invention as claimed is deemed prima facie obvious over the cited references.
Conclusion
No claims are allowed.
Claims 16-19 are free of prior art.
The prior art does not teach or motivate one of ordinary skill in the art to arrive at a specific combination of probe sequences and their 80% homologs as presently claimed.
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.
Inquiries
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Young J. Kim whose telephone number is (571) 272-0785. The Examiner can best be reached from 7:30 a.m. to 4:00 p.m (M-F). The Examiner can also be reached via e-mail to Young.Kim@uspto.gov. However, the office cannot guarantee security through the e-mail system nor should official papers be transmitted through this route.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Gary Benzion, can be reached at (571) 272-0782.
Papers related to this application may be submitted to Art Unit 1681 by facsimile transmission. The faxing of such papers must conform with the notice published in the Official Gazette, 1156 OG 61 (November 16, 1993) and 1157 OG 94 (December 28, 1993) (see 37 CFR 1.6(d)). NOTE: If applicant does submit a paper by FAX, the original copy should be retained by applicant or applicant’s representative. NO DUPLICATE COPIES SHOULD BE SUBMITTED, so as to avoid the processing of duplicate papers in the Office. All official documents must be sent to the Official Tech Center Fax number: (571) 273-8300. Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (571) 272-1600.
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/YOUNG J KIM/Primary Examiner
Art Unit 1637 October 3, 2026
/YJK/
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