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 .
Claim Status
Claims 1-9 are pending.
Claims 1-9 were considered.
Claims 1-9 are rejected.
Priority
The instant application file 3 August 2023 claims foreign priority to application CN202310233664.1 filed 10 March 2023. As such, the effective filing date of the application is 10 March 2023.
Information Disclosure Statement
No IDS was filed.
Drawings
The drawings filed on 3 August 2023 are accepted.
Claim Objections
Claim 3 objected to because of the following informalities:
The claim states “...wherein he digested fragments…”[emphasis added]. The word ‘he’ should be replaced with the word “the” to correct the spelling mistake.
Appropriate correction is required.
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 and 2, and claims 2-9 due to their dependency on claim 1, 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, and claims 2-9 due to their dependency on 1, state “…digesting DNA of a Goji berry sample … the Goji berry sample includes all species of Chinese Goji berry germplasms of 7 species and 3 varieties, germplasms of Korea in northeast Asia and germplasms of Mexico in America.” [Emphasis added.] The specification repeats similar language [0007, 0032], but does not include details on how to include all species in a sample. This phrasing in the claims and specification fails to describe how one skilled in the art would create a sample that includes all species of Goji plants. A reading of this claim indicates one sample that includes all species. As such, claims 1-9 are indefinite.
Claim 2 states that “…a sampling site is from 320 m to 3231 m in altitude.” [Emphasis added.] The specification further references sampling site by stating “ a sampling site is from 320 m to 3231 m in altitude.” [0009, 0032] The specification fails to specify the meaning of a sampling site. A reading of this claim could indicate the location from which individuals are located when taking a sample or the location of the tree from which the sample is taken. As such, claim 2 is indefinite.
Claim 2 states that “…a sampling site is from 320 m to 3231 m in altitude.” [Emphasis added.] The specification further references altitude by stating “from 320 m to 3231 m in altitude” [0009, 0032], “a large altitude” [0032], and “from 320 m in altitude in Jinghe County, Xinjiang to 3231 m in Wulonggou,” [0032] The specification fails to provide a reference point for the term altitude. These phrases in the claims and specification fail to explain how one skilled in the art would apply the meaning of the altitude range provided. A reading of this claim could indicate many relative heights, such as the relative heights of the sample when taken, the geographic area where the source of the sample is located, the individual taking the sample, or the sampling instrument. As such, claim 2 is indefinite.
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, and claims 2-9 due to their dependency on claim 1, 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.
Claim 1 (and dependent claims 2-9) states “…the Goji berry sample includes all species…” [Emphasis added.] In reference to the phrase “all species”, claim 1 and the specification state “all species of Chinese Goji berry germplasms of 7 species and 3 varieties, germplasms of Korea in northeast Asia and germplasms of Mexico in America [0007] and the specification further states “covering not only all species of Goji berry germplasms in China, but also germplasms from northeast Asia, Korea, Mexico, America; including not only recognized Goji berry species and varieties in China, but also China's wild Goji berry and cultivated Goji berry in the provinces of the northwest region, the main source of wild Goji berry species.” [0032] None of these listed descriptors clearly defines how one skilled in the art would sample all Goji berry species nor do they clarify exactly which species would be included in any samples.
Claims 1, and claims 2-9 due to their dependency on claim 1, are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a Goji berry sample from a single variety of Goji berry, does not reasonably provide enablement for a Goji berry sample including all species of Chinese Goji berry germplasms. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
MPEP § 2164.01(a) explains how enablement for the claimed invention can be analyzed:
In order to determine compliance with the enablement requirement of 35 U.S.C. 112(a),
the Federal Circuit developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8
USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors to assess whether any
necessary experimentation required by the specification is "reasonable" or is "undue." These
factors include, but are not limited to:
The breadth of the claims;
The nature of the invention;
The state of the prior art;
The level of one of ordinary skill;
The level of predictability in the art;
The amount of direction provided by the inventor;
The existence of working examples; and
The quantity of experimentation needed to make or use the invention based on the
content of the disclosure.
The Wands factors are analyzed with respect to the claimed invention in turn below.
The claim is broad and refers to “the Goji berry sample includes all species of Chinese Goji berry germplasms of 7 species and 3 varieties, germplasms of Korea in northeast Asia and germplasms of Mexico in America.” There is no explanation as to how to sample all current and future species of Goji berry.
The nature of the invention is creating samples of digested Goji berry DNA.
The state of the art includes evolutionary ancestry models based on individual genetic samples from a variety of species. The Wildlife Forensic DNA Standards references in multiple places the significance of DNA samples being sourced from one individual in forensic studies. (NIST OSAC draft document, 2017, pages 0-14) Specifically, this ASB standards document indicates “variations in the DNA sequence between individuals permits DNA testing to distinguish individuals from each other” and “extracted DNA is total cellular DNA isolated from a biological sample.” (Page 6, sections 3.9 and 3.10)
While one skilled in the art would be familiar with how to do ancestry studies from comparisons between individual species’ DNA samples, there is no method for doing ancestry analysis on a sample that includes DNA from all species.
The level of predictability in the art is high as the evolutionary ancestry of the Goji berry is unknown. As indicated in the specification “the origin of Lycium species in the world academic community has been inconclusive. There are a variety of theories… These theories are based on the investigation of the botanical traits of Lycium, and the requirements for samples are not clear enough, resulting in a gap in the study on the original ancestry and genetic evolution of Lycium.” [0004]
The specification provides no guidance on how to create and use a DNA sample of Goji berry where the sample includes all species of Gogi berry.
No working examples are provided in the specification for the sampling method of claim 1.
With no guidance from the specification, it would require an undue amount of
experimentation to determine how to use the method of claim 1.
In view of the Wands factors discussed above, the disclosure of the instant application does not
reasonably enable a person having ordinary skill in the art to use the full scope of the claimed
invention.
Claim Interpretation
For the purpose of applying prior art:
A Goji berry sample is interpreted as containing DNA from one Goji berry species.
A sampling site is interpreted as the location on the tree from which the sample is taken.
The term “altitude” is interpreted as the height above sea level.
Samples are taken from at least one of any known Gogi berry species.
Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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.
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 1-7 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al (Biochemical Genetics, 6 June 2018, pages 575-585) in view of Zhao et al (Frontiers in Plant Science, 7 August 2019, pages 1-11). (Herein referred to as Zhang and Zhao, respectively.)
With respect to claim 1, and dependent claims 2-7, Zhang teaches obtaining phylogeny results from 19 accessions of Chinese wolfberry (Goji berry) germplasm based on RAD-seq markers. (Page 575, Abstract) Zhang further teaches genomic DNA was digested and the libraries were sequenced by Illumina HiSeq platform (high-throughput sequencing). (Page 578, lines 7-8 and 20) Zhang additionally teaches variant calling was performed and SNP sites were filtered. (Page 579, lines 15-18) Zhang teaches that SNP sites were used for phylogeny results and genetic structure analysis. (Page 580, lines 8-9)
Zhang does not teach restriction endonucleases RsaI and HinCII.
Zhao teaches the prepared genomic DNA samples from wolfberry (Goji) individuals were digested using a combination of RsaI and HinCII. (Page 3, lines 25-27)
With respect to claim 2, Zhang and Zhao teach the limitations of claim 1 as described above. Zhang further teaches all the accessions were conserved with cutting propagation in the Germplasm Nursery of Qinghai Gouqi (Nuomuhong Co., Qinghai province, China), from which mature plant material was supplied. The Nuomuhong Farm is known to be at an elevation of 2780 m above sea level. (Nuomuhong Farm website, machine translated, page 1)
Zhang does not specifically disclose the meaning of “mature plant material” and therefore does not explicitly teach Goji berry samples from trees that are from 3 to 156 years old.
Zhao teaches sample data was recorded for 3 consecutive years (page 2, right column, last paragraph) and samples were grown and collected in Ningxia Academy of Agriculture and Forestry Sciences, National Wolfberry Germplasm Resources Garden, Ningxia, China (page 2, right column, third paragraph). According to the Baidu Encyclopedia, Ningxia Academy of Agriculture and Forestry Sciences is at an altitude of 1100 m (Machine translated webpage, page 2).
With respect to claim 3, Zhang and Zhao teach the limitations of claim 1 as described above. Zhang teaches fragments ranging in length from 200 to 400 bp and 400–600-bp-sized were collected. (Page 578, paragraph 2)
Zhang does not specifically teach digested fragments that are 364-414 bp.
Zhao teaches Restriction-ligation-PCR products of 364–414 bp. (Page 3, right column, line 1)
With respect to claim 4, Zhang and Zhao teach the limitations of claim 1 as described above. Zhang teaches analyzing the quality of the libraries, checking the insert size of the libraries, performing Q-PCR to detect the effective concentration of libraries, and sequencing of the libraries by Illumina HiSeq 2500 platform. (Page 578, lines 15-21)
Zhang does not explicitly teach the combined limitations of A-tailing, ligation with adaptors, PCR amplification, purification, mixing, and gel cutting to select target fragments.
Zhao teaches Nucleotide (A) and duplex tag-labeled sequencing adapters were added to the digested products, polymerase chain reaction (PCR) was performed, Restriction-ligation-PCR products (364–411 bp) were excised and purified using a gel extraction kit, and gel-purified products from each sample were pooled and subjected to cluster generation and sequencing using an Illumina HiSeq platform. (Page 3, left column, last paragraph to right column, first paragraph) Zhao further teaches sequencing data were quality controlled. (Page 3, right column, line 11)
With respect to claim 5, Zhang and Zhao teach the limitations of claims 1 and 4 as described above.
Zhang does not teach sequencing data identified by dual-index or evaluating sequencing quality and data volume after filtration of adaptors.
Zhao teaches duplex tag-labeled sequencing adapters were added to the digested products (dual-index) (page 3, left column, last paragraph) and the remaining reads were sorted by individual using duplex barcode sequences before trimming the barcodes (filtration) (page 3, right column, lines 15-17). Zhang further teaches the results of high-throughput SLAF sequencing generated sufficient clean pair-end reads and reads per individual with Q30 average of 95.15% indicating that a sufficient volume of high-quality source data was generated. (Page 4, left column, last paragraph)
With respect to claim 6, Zhang and Zhao teach the limitations of claim 1 as described above.
Zhang does not explicitly teach acquiring SNP markers, but does teach developing and using RAD-seq markers (page 575, Abstract) and the identification and use of SNP sites (page 579, paragraph 2). Zhang discloses that the restriction site-associated DNA (RAD-seq) method can identify polymorphic variants in genomic regions and can provide thousands of genome-scale SNP sites. (Page 577, lines 11-14)
Zhang does not teach polymorphic SLAF tags.
Zhao teaches polymorphic SLAF tags and SNP markers. (Page 3, right column, lines 23-25 and 36-37)
With respect to claim 7, Zhang and Zhao teach the limitations of claims 1 and 6 as described above.
Zhang does not teach acquiring SLAF tags by clustering sequencing reads from different Goji berry samples based on sequence similarity.
Zhao teaches clean sequencing reads were analyzed to group SLAF reads with parameter similarity. (Page 3, lines 17-25)
It would have been prima facie obvious to one of ordinary skill in the art at the effective filing date of the invention to have combined the method of Zhang using RAD-seq to identify polymorphisms markers for phylogeny analysis with the method of Zhao using SLAF sequencing and SNPs. Zhao teaches that for species without a reference genome, restriction enzyme digestion-based methods, such as RADseq and SLAF-seq, are effective for finding genome-wide SNPs. (Page 2, left column, last paragraph) Zhao further teaches that SLAF-seq has proven to be an efficient technique for large-scale de novo SNP discovery and genotyping using high-throughput sequencing platforms and it provides a high-resolution strategy for large-scale genotyping and genetic map generation for many species. (Page 2, left column, last paragraph) Zhao additionally teaches that SLAF-based genetic maps have been reported in different perennial woody plants. (Page 2, left column, last paragraph) Therefore, one of ordinary skill in the art would have been motivated to substitute the RAD-seq method of Zhang with the SLAF-seq method of Zhao when looking for SNPs for phylogenetic analysis. One of ordinary skill in the art would have had a reasonable expectation of success in finding SNPs when substituting RAD-seq with SLAF-seq. The additional limitations of claims 1 and 3-7 that are taught by Zhao are known components and steps of the SLAF-seq protocol. It would have been further obvious, regarding claim 2, to clearly specify the age of the Goji germplasm samples and for these samples to be taken from trees that are mature. Utah State University Extension service states that Lycium barbarum will not reach full production for 3 to 5 years. (Fact sheet, October 2015, page 1) The invention is therefore prima facie obvious.
Claims 8 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang and Zhao, and further in view of He et al. (Journal of Nanjing Forestry, 2 March 2022, pages 81-71) (Herein referred to as He.)
With respect to claim 8, Zhang and Zhao teach the limitations of claims 1 and 6 as described above. Zhang teaches sequencing reads were aligned to the reference genome using BWA software, the aligned reads were converted to BAM files using SAMtools software, and variant allele calling was performed for each individual using SAMtools. (Page 579, second paragraph) Zhang further teaches mapping based on high depth. (Page 580, paragraph 2) Zhao teaches SNP markers based on SLAF-tags with high depth. (Page 6, Table 5)
Zhang and Zhao do not teach a high depth SLAF-tag as a reference sequence, developing SNPs with GATK and SAMtools, and finding SNP markers based on results found with both GATK and SAMtools.
He teaches the sequence type with the highest sequencing depth in the SLAF tag is used as the reference sequence, developing SNPs using both GATK and SAMtools methods, and the intersection of SNP tags obtained by the two methods is used as the final reliable set of SNP markers. (Page 83, right column, lines 2-6)
With respect to claim 9, Zhang and Zhao teach the limitations of claim 1 as described above. Zhang teaches a phylogeny tree and genetic structure analysis. (Page 579, paragraph 3; page 580, paragraphs 2 and 3; and page 581, Figure 1)
Zhang and Zhao do not teach population structure analysis, principal component analysis, and linkage disequilibrium analysis.
He teaches a phylogenetic tree and principal component analysis. (Page 84, right column, last paragraph; Page 85, Figure 2) He further teaches population structure analysis. (Page 83, right column, line 20) He additionally teaches using GenAIEx 6.5 software for data analysis based on the number of effective alleles, the number of loci (Ne), proportion of polymorphic sites (PPL), observed heterozygosity (Ho), and expected heterozygosity (He). (Page 83, right column, lines 9-11) Blyton and Flanagan disclose that GenAIEx 6.5 software was known before the effective filing date as a tool for linkage disequilibrium analysis and such analysis would utilize the types of data listed above as referenced in He. (A Guide to GenAIEx 6.5, 1 August 2017, pages 1-122) (Pages 38-39)
It would have been prima facie obvious to one of ordinary skill in the art at the effective filing date of the invention to have combined the methods of Zhang and Zhao as described above with the additional phylogenetic analysis methods of He. He discloses some objectives of their phylogeny study of specific oak trees were to analyze the genetic diversity and structure of different varieties to reveal their genetic differentiation characteristics and genetic
relationships among individual trees, and to provide a theoretical basis for conservation and breeding. (Page 81, Abstract) He teaches domestic research on introduced oak species is still limited to conventional breeding, and research on the genetic basis and phylogenetic relationships of different foreign oak germplasm resources remains relatively lacking. (Page 82, left column, last paragraph) He further teaches that genetic diversity is the foundation of species evolution and adaptation and a core component of genetic structure research. (Page 82, right column, first paragraph) He additionally states that the study of genetic structure has extremely important theoretical and practical significance for the discovery, utilization, and protection of germplasm resources. (Page 82, right column, first paragraph) Zhang discloses that factors have limited the modern breeding of Chinese wolfberry (Goji). (Page 576, last paragraph) Zhang further states that the limited genetic background of Chinese wolfberry (Goji) could increase the risk of disease problems, and the relative lack of germplasm resources will restrict the development of wolfberry breeding and slow the development of lines exhibiting high yield and high quality as demanded by consumers. (Page 577, lines 3-7) Therefore, one of ordinary skill in the art would have been motivated to adapt the phylogeny study of oak trees to the phylogeny study of Goji trees. In both cases, there are economic and scientific motivations to better understand the genetic relationships between different varieties. It would have been obvious to one of ordinary skill in the art to have applied the methods used by He to the study by Zhang with a reasonable expectation of success in gaining more insight to the phylogenetic relationships among Goji berry species. It would have been additionally obvious to incorporate known tools (such as GATK and SAMtools) to develop SNP markers using high depth SLAF tags as reference sequences. He discloses genetic diversity and genetic structure analysis of oak populations was conducted using SLAF-sec technology with the aim to develop a batch of usable SNP markers to provide a theoretical basis for the development, utilization and protection of germplasm resources and as a useful reference for the research of other tree species. (Page 85, left column, last paragraph) These techniques and applications using SLAF-seq would have been obvious to apply with a reasonable expectation of success to other tree species, such as Goji berry. Further, one of ordinary skill in the art would have been motivated to include the known phylogenetic research methods of phylogenetic tree analysis, population structure analysis, principal component analysis and linkage disequilibrium analysis in a phylogeny study of Goji berry trees. In addition to these methods being used by He, they were known in the art before the effective filing date of the invention as indicated in a study of tea plants by Zhifei Zhao et al. (BMC Plant Biology, 27 January 2022, pages 1-14) (Page 1, Abstract: Results) The invention is therefore prima facie obvious.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Li et al teaches analysis of genetic diversity for wolfberry germplasm using AFLP. (Chinese Traditional and Herbal Drugs, April 2011, pages 770-773) Wang et al teaches AFLP analysis of population genetic diversity of wild Lycium ruthenicum. (Journal of Plant Ecology, 1 October 2015, pages 1003-1011) Yin et al teaches genome-wide identification of microsatellite markers and their application in genetic studies of wolfberry. (bioRxiv, 25 May 2022, pages 1-23) Qian et al teaches research progress on interspecies relationships and the origin of cultivated goji berries in China. (China Journal of Traditional Chinese Medicine, 20 March 2017, pages 3282-3285) Cao et al teaches wolfberry genomes and the evolution of Lycium. (Communications Biology, 3 June 2021, pages 1-13)
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/S.L.G./Examiner, Art Unit 1687
/Karlheinz R. Skowronek/Supervisory Patent Examiner, Art Unit 1687
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