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 .
Election/Restrictions
Applicant’s election of Group I in the reply filed on October 29, 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 21-25 and 27-31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 September 27, 2021 is proper and is being considered by the Examiner.
Drawings
The drawings received on September 27, 2021 are acceptable.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. 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 (www). For example, see section [0068] disclosing the link, “www.mplpa.com”. See MPEP § 608.01.
Claim Rejections - 35 USC § 112
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 1-20 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 1 is indefinite because the claim recites a preamble that the kit comprises a probe set that is capable of distinguishing among variously recited lymphomas, but then recites that the probe set actively comprises that which “is capable of detecting the RNA expression of at least one marker from tumor cells of a lymphoma and at least one marker from bystander non-tumor cells located in a microenvironment of said lymphoma,” confusing whether the probe set is capable of detecting the RNA expression (as actively required) or distinguishing among various lymphomas (as recited in the preamble).
Claims 2-20 are indefinite by way of their dependency on claim 1.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 14, 15, and 20 are rejected 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. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a Written Description Rejection.
The written description requirement ensures that, “an applicant invented the subject matter which is claimed. Further, the written description requirement for a claimed genus may be satisfied through a sufficient description of a representative number of species by 1) reduction to practice; 2) reduction to drawing; or 3) disclosure of relevant identifying characteristics (i.e., structure of other physical and/or chemical properties, functional characteristics coupled with a known or disclosed correlation between function and structure) (MPEP 2163 at II(A)(3)(a)(ii)).
Reduction to Practice
The Federal Circuit reiterated that mere use of the same words in the specification and the claim (an in ipsis verbis test) is not sufficient to establish written description.
Claim 1 is directed to a kit comprising a set of probes which can distinguish among various types of lymphomas as recited.
The specification discloses various combinations of identified markers (sections [0058]-[0066]
However, these lists of markers disclosed in the specification is not a reasonable number of species so as to justify a generic probe set comprising a set of probes that essentially is “capable of detecting” an RNA expression of at least one marker from tumor cells of lymphoma and that which is capable of distinguishing among different recited lymphoma subtypes in claim 1, that includes any and all probes for such markers which has yet to be identified.
Reduction to Drawing
The specification discloses the list of markers referenced above (see Figure 1A-1F and their expressions). However, the list is not sufficient deemed to be representative of the genus as presently claimed.
Disclosure of Relevant Identifying Characteristics
While one could argue that a skilled artisan would be able to identify the “representative number of species” of such markers, such method would not satisfy the written description for the genus claims when, “the claims require an essential or critical feature which is not adequately described in the specification and which is not conventional in the art or known to one of ordinary skill in the art” (MPEP 2163(I)(A)). For the claims at issue, such essential or critical feature is at least the markers that is capable of distinguishing among the recited subtypes of lymphomas form which the probe can be derived. Applicants have not disclosed enough number of species within the claimed genus which embraces a polynucleotide across different species comprising an entire DGAT gene, harboring any polymorphism therein.
As stated in University of California v. Eli Lilly and Co. at page 1404:
An adequate written description of a DNA ... "requires a precise definition, such as by structure, formula, chemical name, or physical properties," not a mere wish or plan for obtaining the claimed chemical invention. Fiers v. Revel, 984 F.2d 1164, 1171, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993). Accordingly, "an adequate written description of a DNA requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it; what is required is a description of the DNA itself." Id. at 1170, 25 USPQ2d at 1606.
Therefore, for the foregoing reasons, the genus embraced by the claims is not sufficiently described by the number of species disclosed in the specification, and therefore, the specification lacks written description of the claims.
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 1-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to the judicial exception of naturally occurring phenomenon without significantly more. 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.
Claim Rejections - 35 USC § 102
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.
Claims 1-14 are rejected 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”).
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.
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.
Claim 20 is rejected 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).
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.
Claims 1, 4, 14, 15, and 20 are rejected 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).
With regard to claims 1 and 4, Zekri et al. teach a method of gene expression profiling, wherein the artisans teach a microarray comprising a probe sequence targeting CCND1 (“cDNA microarray analyses revealed suggestive association for 37 genes up-regulated with overall, and 46 genes with DLBCL lymphoma but no significant association with any other follicular lymphomas … up-regulated gene are BCL6, BCL2L, BCL7A, MYC and CCND1, Rb binding protein 5, DKFZP586J1624, Protein kinase inhibitor gamma, Zinc finger protein 3, Choline ethanolamine, phosphor-transferase CEPT1, Protein phosphatase, Histone deacetylase-3 as in Figure 1”, page 4395, 2nd column to page 4396, 1st column, 1st paragraph).
While Zekri et al. teach that the marker the above-discussed markers can be assayed utilizing a probe set, the artisans do not explicitly teach that the probe is an RNA molecule that is 40 to 200 nucleotides long (claims 14 and 15), or a kit further comprising a ligase is employed (claim 20).
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 Zekri et al. with the conventional knowledge available to one of ordinary skill in the art in the field of molecular diagnostics such as Yusenko et al. thereby arriving at the invention as claimed for the following reasons.
With regard to the packaging of the probe set of Zekri et al. with a ligase into a kit, doing so would have been obvious because multiple reagents packaged in 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 probe set of Zekri et al. would have benefited said one of ordinary skill in the art for purposes not necessarily limited to the use of the probe set.
With regard to the probe set being an RNA molecule having lengths of 40 to 200 nucleotides long, the artisans teach a reverse transcription of the expressed markers (see page 4394, “[f]luorescent cDNA, labelled with the Cy3 dye … were prepared from each cancer mRNA sample”) which would have required an RNA molecule of the markers comprising 40 to 200 nucleotides of bases for the reverse transcription process.
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.
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.
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.
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/YOUNG J KIM/Primary Examiner
Art Unit 1637 April 17, 2026
/YJK/
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