DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on November 18, 2025 has been entered. Applicant’s remarks and amendments have been fully and carefully considered but are not found to be sufficient to put the application in condition for allowance. Any rejections or objections not reiterated herein have been withdrawn.
3. Claim 1 is currently pending and has been examined herein.
Claim Rejections - 35 USC § 101
4. 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.
Claim 1 is rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exceptions without significantly more.
Step 1: The claim is directed to the statutory category of a composition of matter.
Step 2A, prong one: Evaluate Whether the Claim Recites a Judicial Exception
The claim is drawn to a kit comprising primers for detecting DNA methylation levels of 350 CG ID’s, wherein the primers for cg04398282 comprise SEQ ID NOs: 16-20. The claim encompasses generic primers for 349 CG ID’s and particular primers for CG ID’s cg04398282.
The generically recited primers for the 349 CG ID’s broadly encompass nucleic acid sequences that occur in nature.
SEQ ID NOs: 16-20 are nucleic acid sequences that contain wildcards. For example R can stand for A or G and Y can stand for C or T. SEQ ID NOs: 16-20 encompass sequences which occur in nature as demonstrated by the following alignments with the natural sequence of the STAP1 gene (NG_047142 May 12, 2016).
The following is an alignment of SEQ ID NO: 16 (when all the Y’s are changed to C) and STAP1.
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276
1070
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The following is an alignment of SEQ ID NO: 17 (when the R is changed to G) and STAP1.
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266
1068
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The following is an alignment of SEQ ID NO: 18 (when the second Y is changed to T and all the other Y’s are changed to C) and STAP1.
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252
1076
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The following is an alignment of SEQ ID NO: 19 (with all the R’s changed to G) and STAP1.
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312
1086
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The following is an alignment of SEQ ID NO: 20 (with all the Y’s changed to C) and STAP1.
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270
1070
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The markedly different characteristics analysis has been used to determine if the nature based products (the primers) are an exception. The nature based products (the primers) have been compared to their natural counterparts. There is no indication that the primers have any characteristics that are different from naturally occurring nucleic acids. There is no difference in function, structure, or other properties. It is noted that the primers are recited as being present in a kit. However the claims do not require that the primers in the kit interact with each other. There is no indication that the primers being present in a kit changes the function, structure, or other properties of the primers. Because the claimed primers do not have markedly different characteristics, they are a product of nature exception.
Step 2A, prong two: Evaluate Whether the Judicial Exception Is Integrated Into a Practical Application
The only element in addition to the natural product is the “kit”. The natural products being present in a “kit” fails to meaningfully limit the claims and is equivalent to adding the words “apply it” to the judicial exception. Accordingly there are no additional elements that integrate the recited judicial exceptions into a practical application.
Step 2B: Evaluate Whether the Claim Provides an Inventive Concept
The only element in addition to the natural product is the “kit”. At the time the invention was made, kits comprising reagents for detecting DNA methylation were well-established, routine, and conventional. Thus, the claims as a whole do not amount to significantly more than each “product of nature” by itself, and the claims do not quality as eligible subject matter.
Response To Arguments
5. In the response the Applicants traversed the rejection under 35 USC 101. The Applicants note that claim 1 as amended recites that the primers for cg04398282 comprise SEQ ID NOs: 16- 20. The Applicants argue that these primers were intentionally designed sequences tailored to optimize PCR amplification, including considerations of GC content, melting temperature, and avoidance of secondary structures. These primers are not random or naturally occurring sequences, but rather the product of human ingenuity designed for a specific diagnostic application. Moreover, the combination of SEQ ID NOs: 16-20 as used in the claimed kit likewise goes beyond what is found in nature, as such a coordinated set of artificial primer sequences does not occur naturally and has been purposefully designed to function synergistically in the claimed kit.
This argument has been fully considered but is not persuasive. The alignments above show that the claimed nucleic acids have the same nucleotide sequences as the naturally occurring STAP1 gene. The claimed nucleic acids have a different structural characteristic than naturally occurring STAP1, because the chemical bonds at each end were severed in order to isolate it from the chromosome on which it occurs in nature, but has the same nucleotide sequence as the natural gene. The claimed nucleic acids have no different functional characteristics. Under the holding of Myriad, the isolated but otherwise unchanged nucleic acids are not eligible because they are not different enough from what exists in nature. In other words, the claimed nucleic acids are different but not markedly different, from their natural counterpart in its natural state (STAP1).
It is further noted that in 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. Thus it is maintained that the claimed primers are a product of nature exception.
It is noted that SEQ ID NOs: 16-20 are present in a kit with primers for detecting 349 other CG IDs. The combination of primers fails to yield sequences which are markedly different from products of nature. See id.; Funk Bros. Seed Co. v. Kalo Inoculant Co., 333 U.S. 127, 131, 68 S.Ct. 440 (1948) (“[H]owever ingenious the discovery of that natural principle may have been, the application of it is hardly more than an advance in the packaging of the inoculants.”); Association for Molecular Pathology v. Myriad Genetics, Inc., 133 S.Ct. 2107, 2117 (2013) (Supreme Court “considered a composition patent that claimed a mixture of naturally occurring strains of bacteria” and held that “the composition was not patent eligible because the patent holder did not alter the bacteria in any way.”); Id. at 2117-18 (purification “is not an act of invention.”) In sum, the claims are directed to naturally occurring sequences without significantly more. Applicants should consider amending the primers to recite non-natural sequences or other substances on the primer(s).
Claim Rejections - 35 USC § 112(b)
6. 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.
Claim 1 is 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 rejected over the recitation of:
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710
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The claim is considered indefinite because the claim contains information in parentheses. Parentheticals make the claims indefinite because it is unclear whether the information in the parentheses has the same, less, or more weight as the rest of the claim language. This rejection may be overcome by deleting the information in parentheses.
7. Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMANDA HANEY whose telephone number is (571)272-8668. The examiner can normally be reached Monday-Friday, 8:15am-4:45pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Shen can be reached at 571-272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/AMANDA HANEY/Primary Examiner, Art Unit 1682