DETAILED CORRESPONDENCE
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 .
This action is in response to the papers filed January 5, 2026. Currently, claims 2, 4, 6, 8, 10-14 are pending. Claims 2, 6, 10-12 have been withdrawn as drawn to non-elected subject matter.
All arguments have been thoroughly reviewed but are deemed non-persuasive for the reasons which follow. This action is made FINAL.
Any objections and rejections not reiterated below are hereby withdrawn.
Election/Restrictions
Applicant's election of Group I, Claims 1, 3-4, 7-8 in the paper filed September 30, 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 § 818.03(a)).
The requirement is still deemed proper and is therefore made FINAL.
Priority
This application claims priority to foreign priority document CHINA 202211167492.4, filed September 23, 2022.
It is noted that a translation of the foreign document has not been received.
Drawings
The drawings are acceptable.
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 4, 8, 13-14 are rejected under 35 U.S.C. 101 because the claimed invention is not directed to patent eligible subject matter. Based upon an analysis with respect to the claim as a whole, the rejected claim(s) do not recite something significantly different than a judicial exception. The rationale for this determination is explained below:
Briefly, 4, 8, 13-14 are rejected because these claims are drawn to a nucleic acid molecule comprising a molecular marker of Ganoderma lucidum strain HMGIM-M624. Claims 4, 8, 13-14 are directed to nucleic acid fragments from the Ganoderma lucidum genome, i.e. known naturally occurring nucleic acids. The specification teaches the molecular marker described in the present invention is an InDel molecular marker with a base sequence (CATGCTGTA) deletion at the 246451"-246460" site of the chromosome sca34 of the high-quality Ganoderma lucidum strain HMGIM-M624. The accession number of the G. lucidum genome which contains the chromosome sca34 is PRJNA71455 in NCBI (page 5, para 16).
Such isolated nucleic acid molecules, that are identical to fragments of naturally occurring nucleic acid molecules are not patent eligible subject matter, i.e. they are judicial exceptions to patentable subject matter.
MPEP 2106.04(b)(II) discusses products of nature. The MPEP specifically discusses DNA, primers and probes. The isolated DNA of Myriad and the primers of Ambry Genetics were described as products of nature by the courts. Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 133 S. Ct. 2107, 2116-17, 106 USPQ2d 1972, 1979 (2013); University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 758-59, 113 USPQ2d 1241, 1243 (Fed. Cir. 2014). The MPEP further states the “product of nature exceptions include both naturally occurring products and non-naturally occurring products that lack markedly different characteristics from any naturally occurring counterpart. See, e.g., Ambry Genetics, 774 F.3d at 760, 113 USPQ2d at 1244 ("Contrary to Myriad's argument, it makes no difference that the identified gene sequences are synthetically replicated. As the Supreme Court made clear, neither naturally occurring compositions of matter, nor synthetically created compositions that are structurally identical to the naturally occurring compositions, are patent eligible.").” The Federal Circuit in Ambry Genetics reviewed “[t]he Supreme Court held ineligible claims directed to segments as short as 15 nucleotides, the same length as the primer claims at issue here, suggesting that even short strands identical to those found in nature are not patent eligible. Compare ’492 patent col. 170 ll. 32–38, with ’282 patent col. 153 ll. 66–67.”
In the instant case, the claims, embrace markers, probes and primers that are identical to naturally occurring genome fragments and clearly read on nature-based products that themselves do not exhibit markedly different characteristics from the naturally occurring gene. See e.g. Myriad in which one claim at issue was drawn to “[a]n isolated DNA having at least 15 nucleotides [an isolated DNA coding for a BRCA1 polypeptide having the amino acid sequence of SEQ ID NO: 2] (Myriad at 2113). The Court recognized that this claim, if valid, would have given Myriad exclusive right to isolate any strand of 15 or more nucleotides of an individual’s BRCA1 gene (paragraph bridging 2113 and 2114). This is directly analogous to the instant situation wherein Applicant’s claims cover probe and primer molecules that are fragments of a naturally occurring Ganoderma lucidum genome sequence. The Court held that “[a] naturally occurring DNA segment is a product of nature and not patent eligible merely because it has been isolated”, and that “Myriad’s claims are not saved by the fact that isolating DNA from the human genome severs the chemical bonds that bind gene molecules together” (page 2118). The Court found that while Myriad had located and sequenced an important gene, Myriad had not created anything, and that “separating that gene from its surrounding genetic material is not an act of invention” (page 2118). Consistent with the findings of the Court in Myriad, the Office finds that the primers and probe molecules embraced by the instant clams are not patent eligible compositions of matter regardless of whether or not they are isolated from the genome. The Guidelines indicate that a change in biological function or activity maybe a characteristic of an isolated product that can provide a marked difference sufficient to distinguish over a naturally occurring product. However, in this case, as in the Ambry case, the function of the nucleic acids is the same function as the relevant portion of the naturally occurring sequence. Just as in nature, primers and probes utilize the innate ability of DNA to bind to itself.
Having established that the claims include a naturally occurring product that is a judicial exception, it must now be determined whether or not the claims recite an element or combination of elements that amount to significantly more than that exception, and whether those additional elements also amount to significantly more for the other claimed exception(s), which ensures that the claim does not have a preemptive effect with respect to any of the recited exceptions. To determine whether a claim that includes a nature-based product limitation recites a “product of nature” exception, an analysis is performed in which it is first determined if a claim includes a nature-based product that has markedly different characteristics from the corresponding naturally occurring product, and if it does not, then it is determined whether or not other elements of the claim are sufficient to ensure that the claim as a whole amounts to significantly more than the exception itself (see the Interim Guidance on Patent Subject Matter Eligibility published 12/16/2014 in the Federal Register at pages 74618-74633). In order to be markedly different, the claimed product must possess at least one characteristic that is different from that of the counterpart.
In the instant case, claim 8 recites an additional element as a kit, i.e. a reaction tubes, containers, vials. None of these limitations provides any significant addition to the judicial exceptions already claimed that would prevent the claims from having a pre-emptive effect on the use of the judicial exception. The presence of a “tube" in a kit composition comprising a nucleic acid is entirely conventional and does not represent a modification that amounts to something significantly more than the judicial exception.
The fact that these natural products are organized into a kit with an intended use adds nothing to the judicial exceptions that would distinguish them from the naturally occurring material. Similarly, a claim to a kit in which one of the kit elements is naturally-occurring product that is separate and distinct from the other kit elements would forestall the use of that naturally occurring product.
Claims 13-14 are further directed to PCR reagents including Taq Master mix and ddH20. These additional elements are not significantly more. As explained in Examples 10 and 28 of the 101 Guidelines, a kit comprising two naturally occurring components does not become patent eligible. The nucleic acid primers are naturally occurring, as discussed above. The PCR reagents such as enzymes and water are also naturally occurring. The components are not mixed in the kit, but instead are separate from each other. Their inclusion in the same kit does not change their characteristics. Although the user of the kit may choose to mix the nucleic acids and Taq master mix and ddH20 at some time in the future, the mixture, which may or may not exist in the future is not a part of the claimed invention. The nucleic acids, Taq polymerase and ddH20 do not have markedly different characteristics from their natural counterparts in their natural state, and are “product of nature” exceptions. Therefore, the claims are properly rejected under 35 USC 101 as being drawn to patent-ineligible subject matter.
Response to Arguments
The response traverses the rejection. The response asserts the claims have been amended to be a reagent includes a specific primer pair. This argument has been considered but is not convincing because probe and primer to naturally occurring sequences are not patent eligible.
MPEP 2106.04(b)(II) discusses products of nature. The MPEP specifically discusses DNA, primers and probes. The isolated DNA of Myriad and the primers of Ambry Genetics were described as products of nature by the courts. Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 133 S. Ct. 2107, 2116-17, 106 USPQ2d 1972, 1979 (2013); University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 758-59, 113 USPQ2d 1241, 1243 (Fed. Cir. 2014). The MPEP further states the “product of nature exceptions include both naturally occurring products and non-naturally occurring products that lack markedly different characteristics from any naturally occurring counterpart. See, e.g., Ambry Genetics, 774 F.3d at 760, 113 USPQ2d at 1244 ("Contrary to Myriad's argument, it makes no difference that the identified gene sequences are synthetically replicated. As the Supreme Court made clear, neither naturally occurring compositions of matter, nor synthetically created compositions that are structurally identical to the naturally occurring compositions, are patent eligible.").” The Federal Circuit in Ambry Genetics reviewed “[t]he Supreme Court held ineligible claims directed to segments as short as 15 nucleotides, the same length as the primer claims at issue here, suggesting that even short strands identical to those found in nature are not patent eligible. Compare ’492 patent col. 170 ll. 32–38, with ’282 patent col. 153 ll. 66–67.”
The response does not provide any arguments why these segments of 20 nucleotides, namely SEQ ID NO: 1 and 2, are not naturally occurring products.
Claims 13-14 that add additional reagents do not overcome the 101 rejection, for the reasons provided above.
Thus for the reasons above and those already of record, the rejection is maintained.
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.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Claim(s) 4, 8, 13 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by NEB catalog (1998/1999), pp. 121, 284.
Claim 4 is directed to a molecular marker of the high-quality Ganoderma lucidum strain HMGIM-M624. The claims nor the specification provide any length limitations for the molecular marker. Claims 4 are directed to reagents, such as primers. With respect to Claim 4, “shown in” encompasses fragments of the 20bp primers of SEQ ID NO: 1 and 2.
The NEB catalog offered for sale a random primer mix of 12mer and 24mer nucleotide primers. As the calculation below shows, about 3.2 x 108 molecules of every 12-mer and about 9 molecules of every single 24 mer are present in each tube of the 24 nucleotide mixtures.
a. Molecular weight of 12-mer:
12 x 325 daltons/nucleotide = 3,900 daltons = 3,900 g/mol
b. Total number of possible 12-mers:
412 = 1.6 x 107 molecules
c. How many molecules of 12-mer in a vial sold by NEB:
1 A260 unit = 33 µg = 3.3 x 10-5 g
3.3 x 10-5 g / 3,900 g/mol = 8.4 x 10-9 mol
(8.4 x 10-9 mol) x (6.02 x 1023 molecules/mol) = 5 x 1015 molecules
d. How many molecules of each 12-mer in a single vial:
5 x1015 molecules / 1.6 x 107 molecules = 3.2 x 108 molecules of each 12-mer per vial
e. Molecular weight of 24-mer:
24 x 325 daltons/nucleotide = 7,800 daltons = 7,800 g/mol
f. Total number of possible 24-mers:
424 = 2.8 x 1014 molecules
g. How many molecules of 24-mer in a vial sold by NEB:
1 A260 unit = 33 µg = 3.3 x 10-5 g
3.3 x 10-5 g / 7,800 g/mol = 4.2 x 10-9 mol
(4.2 x 10-9 mol) x (6.02 x 1023 molecules/mol) = 2.5 x 1015 molecules
h. How many molecules of each 24-mer in a single vial:
2.5 x1015 molecules / 2.8 x 1014 molecules = 9 molecules/vial
The claims encompass a large genus of possible nucleic acid markers and primers with no particular base composition or length. The NEB catalog kits will inherently and necessarily contain 12 and 24 nucleotides primers encompassed by the claimed recitation.
Thus, the prior art inherently teaches each and every structural limitation of the instant claim.
Response to Arguments
The response traverses the rejection. The response asserts the claims are directed to specific primers with 20mer designed to match the 9bp deletion site. This argument has been considered but is not convincing because the claims are not directed to primers consisting of SEQ ID NO: 1 and 2. The claims instead are directed to sequences shown in SE QID NO: 1 and 2 which encompasses part of the sequence or fragments, as explained in the claim interpretation section of the rejection.
The claims are directed to products. The NEB kits comprise these products. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. Here the claims encompasses primers that comprise SEQ ID NO: 1 and 2 as well as fragments of SEQ ID NO: 1 and 2. The 12mer and 24mer kits of NEB comprise these claimed primers. The kits of NEB inherently comprise the claimed primers.
Thus, for the reasons above and those already of record, the rejection is maintained.
Conclusion
No claims allowable.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
GDMCC No 60889 November 2019 deposit and NCBI PRJNA71455, November 7, 2019 is the high-quality Ganoderma lucidum strain HMGIM-M624 described in reagents for detecting the molecular marker was preserved in Guangdong Microbial Culture Collection Center (address: 5th Floor, No. 59 Building of No. 100 Yard, Mid. Xianlie 20 Road, Guangzhou City) with the preservation number of GDMCC No: 60889 on November 7, 2019. The molecular marker described in the present invention is an InDel molecular marker with a base sequence (CATGCTGTA) deletion at the 246451"-246460" site of the chromosome sca34 of the high-quality Ganoderma lucidum strain HMGIM-M624. The accession number of the Ganoderma lucidum genome which contains the chromosome sca34 is PRJNA71455 in NCBI.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEANINE ANNE GOLDBERG whose telephone number is (571)272-0743. The examiner can normally be reached Monday-Friday 6am-3:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng (Winston) Shen can be reached on (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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/JEANINE A GOLDBERG/Primary Examiner, Art Unit 1682
February 5, 2026