DETAILED ACTION
This Action is in response to the communication filed on 09/16/2025.
Claims 1-16, 18, 26-27 are pending.
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 (claims 1-13) and the species C. difficile endonuclease recognition site SEQ ID NO: 3, chemically modifying method, and C. difficile infection in the reply filed on 09/16/2025 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Claims 14-16, 18, 26-27 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 09/16/2025.
Claims 1-13 are under consideration.
Claim Objections
Claim 10 is objected to because of the following informalities: claim 10 has two periods at the end of the claim, only one period is proper. Appropriate correction is required.
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 1-13 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon (product of nature) without significantly more. Claim 1 recites, “A composition comprising at least one selected fragment of DNA exogenous to a targeted organism and a carrier, wherein said DNA fragment has at least 50% sequence homology to a DNA sequence of said targeted organism and wherein said fragment comprises no more than 5 unprotected specific endonuclease recognition sites of said targeted organism.” The claimed composition is not markedly different from a fragment of genomic DNA. This judicial exception is not integrated into a practical application because the claims do not provide a modified form of the fragment of genomic DNA that is markedly different from its naturally occurring counterpart. Furthermore, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
Prong 1 - Statutory category: Here, the claimed invention is either a composition of matter or a manufacture. Under 35 USC 101, the claimed invention must be “any new and useful process, machine, manufacture, or composition of matter.” The claimed invention is drawn to a composition comprising a fragment of DNA that has at least 50% sequence homology to a DNA sequence of a targeted organism and wherein said fragment comprises no more than 5 unprotected specific endonuclease recognition sites of said targeted organism, which can be considered a composition of matter or a manufactured product. Therefore, the claimed fragment of DNA falls under one of the statutory category identified in 35 USC 101.
Prong 2A – Judicial exception: Here, the claimed invention is a composition or a manufactured product but is directed to a natural phenomenon (product of nature), which is a judicial exception. Even a composition or a manufacture may not be patent eligible if it falls under a judicial exception. The three judicial exception categories are enumerated abstract idea, a law of nature, or a natural phenomenon (product of nature). Nature based products include both naturally occurring as well as non-naturally occurring products that have characteristics not markedly different from a natural occurring counterpart, and both fall within the judicial exception. It is noted that the Federal Circuit in University of Utah Research Foundation v. Ambry Genetics (Fed. Circ. December 2014) held that claimed synthetically made primers that have the identical nucleotide sequences as portions (i.e., fragments) of naturally occurring nucleic acids are ineligible nature-based products. The court reasoned that simply being synthetic or non-naturally created is not enough for eligibility, when the identical sequences occur in nature.
Here, the claimed DNA can exist as, or encompass a natural occurring fragment of genomic DNA. It is noted that the specification discloses in Example 1: “Growth inhibition by genomic DNA from Staphylococcus aureus” (beginning at paragraph [0088] of the specification):
“Genomic DNA was extracted from Staphylococcus aureus by phenol: chloroform extraction and purified using a PD-10 desalting column comprising Sephadex G-25 resin. Cultures of the following strains were prepared as described above and each strain was inoculated to a suitable growth medium as detailed in Table 1… Purified DNA was added to each culture at one of the following concentrations: 0, 5, 25, 50, 100, 200 and 400 ug/ml. Cell growth was determined by optical density (OD) measurements at 600 nm. A linear plot of OD versus DNA concentration was prepared, and the value DNA concentration at which 50% growth inhibition was seen (ID50) was determined. Results are presented in FIG. 1 , showing that the highest inhibition (represented by the lowest concentration of DNA required to provide 50% inhibition) was seen by DNA from S. aureus against itself, while lowest inhibition was seen against E. coli.”; and,
“It was found that autologous DNA from Clostridium tyrobutyricum (Cty) species 1460 (Cty1460) inhibits growth of the microorganism, while DNA from Clostridium butyricum (Cbu) DNA did not inhibit growth of Cty1460, even though it has a high degree of homology. Similar results have been observed in many other strains of Clostridium and related organisms” (See [0015]); and, “Bacteria are protected against self-degradation by endonucleases due to the action of methyltransferase enzyme which can modify DNA by methylation, and thereby protect nucleotides at specific recognition sequences. Methylated DNA is protected from restriction endonucleases.” (See [0019]).
Therefore, it is clear that the claimed DNA composition is a product of nature, as it specifically encompasses genomic DNA extracted from a bacterial cell. Additionally, the disclosure indicates that bacterial cells methylate their DNA in order to protect it from degradation, while unmethylated (i.e., unprotected) DNA will be subject to degradation by endonuclease enzymes present in bacterial cells; thus indicating that DNA extracted from a bacterial cell will be methylated to protect it from endonuclease degradation. The fact that extracted DNA was able to inhibit Cty1460 growth but not Cbu growth is indicative of the DNA being protected from self-degradation (see [0019], as indicated above). Accordingly, and as evidence by the specification, such as in Example 1 beginning at [0085], the claims encompass genomic DNA isolated from a bacterial cell, and is thus a product of nature and is not patent eligible subject matter as it falls within the natural phenomenon (product of nature) judicial exception category.
Prong 2B: Judicial Exception/Significantly More: The “significantly more” analysis is a determination whether a claim is eligible if the claim(s) recites additional elements that integrate the judicial exception into a practical application. Integration requires an additional element in the claim to apply, rely on, or use the judicial exception in a manner than imposes a meaningful limit on the judicial exception.
Claim 1 recites a composition comprising a selected fragment of DNA exogenous to a targeted organism and a carrier, wherein the DNA comprises no more than 5 unprotected specific endonuclease recognition sites. However, the presence of a carrier does not alter the chemical structure of the DNA, thus it does not add significantly more to the DNA, Furthermore, as indicated above, bacterial genomic DNA isolated from a bacterial cell would be naturally be methylated by the bacterial cell, as evidenced by the instant disclosure (e.g., [0019]). The limitation “exogenous to a targeted organism” is a relative limitation such that isolated DNA would be “exogenous” to any organism as it would necessarily be outside (exogenous) to the organism. Therefore, the isolated genomic DNA (or fragment thereof) from Cty1460 (as in [0019]), would be “exogenous” to any organism, including other bacteria of the cell type it was isolated from (e.g., the DNA isolated from Cty1460 in [0019] would be exogenous and essentially fully (100% ) homologous to DNA in other target Cty1460 cells), and it would also be exogenous to any other type of bacteria as well (e.g., isolated Cty1460 DNA would be exogenous to Cbu cells, and vice-versa) It is also noted that [0019] discloses that Cbu DNA and Cty1460 DNA have a high degree of homology. Regarding the limitation that the DNA has no more than 5 unprotected (e.g., unmethylated) endonuclease recognition sites, it is noted that the broad claims, such as claim 1, do not set forth any requirement with respect to the size of the DNA fragment. Thus, the claim encompasses fragments of any size, thus the broad claims, including claim 1, encompass a fragment of bacterial genomic DNA that has less than 5 possible unprotected specific endonuclease sites. Therefore, the limitation that the fragment of DNA has no more than 5 unprotected specific endonuclease recognition sites does not add significantly more to a naturally occurring fragment of bacterial genomic DNA. Nevertheless, even for fragments of genomic DNA which comprise 5 or more possible unprotected endonuclease recognition sites, merely ensuring that unprotected sites are protected does not add significantly more to a natural DNA sequence because as previously indicated, bacterial cells are known to methylate endonuclease recognition sites which protects the DNA from degradation in the bacterial cell.
Therefore, claim 1 is rejected under 35 U.S.C. 101 because the claim is directed to a judicial exception, specifically a natural phenomenon (product of nature) without significantly more.
Regarding claim 2, which requires that the DNA fragment comprises no more than 2 unprotected sites per 1.5 kilobase pairs (kbp) of the DNA fragment, similar to claim 1 as explained above, the claim encompasses a fragment of bacterial genomic DNA that has less than 2 possible unprotected specific endonuclease sites. Therefore, the limitation that the fragment of DNA has no more than 2 unprotected specific endonuclease recognition sites does not add significantly more to a naturally occurring fragment of bacterial genomic DNA. Nevertheless, even for fragments of genomic DNA which comprise 2 or more possible unprotected endonuclease recognition sites per 1.5 kbp, merely requiring that unprotected sites are protected does not add significantly more to a natural DNA sequence because bacterial cells are known to methylate endonuclease recognition sites which protects the DNA from degradation in the bacterial cell.
Regarding claim 3 which requires that the targeted organism comprises a microorganism that can be a Clostridium, the claim does not add significantly more to the natural fragment of genomic DNA described in [0019] which is an isolated genomic DNA that is exogenous to a targeted Clostridium such as Cty1460 or Cbu.
Regarding claim 4, as explained above, the DNA isolated from Cty1460 in [0019] would be exogenous and essentially fully (100% ) homologous to DNA in other target Cty1460 cells and would also be exogenous to target Cbu cells that has DNA with a high degree of homology to Cty1460 DNA.
Regarding claim 5, as indicated above, the Federal Circuit in University of Utah Research Foundation v. Ambry Genetics (Fed. Circ. December 2014) held that claimed synthetically made primers that have the identical nucleotide sequences as portions (i.e., fragments) of naturally occurring nucleic acids are ineligible nature-based products. The court reasoned that simply being synthetic or non-naturally created is not enough for eligibility, when the identical sequences occur in nature.
Regarding claim 6, an isolated fragment that is a synthetic fragment having single stranded DNA overhangs at the 5’ and 3’ ends does not add significantly more the natural sequence, as it was known that adding single stranded overhangs to the ends of DNA fragments can aid in, among other things, incorporating the DNA into a target site. Thus addition of single stranded overhangs to a DNA sequence is well-understood, routine and conventional in the art.
Regarding claim 7, the limitation that the fragment comprises an average of at least 1 methylated endonuclease recognition site per 1.5 kbp does not add significantly more to a naturally occurring fragment of bacterial genomic DNA because methylation of endonuclease recognition sites was well-known natural mechanism for protection of bacterial cell DNA.
Regarding claim 8, the claim does not require any specific size for the DNA fragment, thus given the broadest reasonable interpretation (BRI), the claim encompasses very large fragments of genomic DNA, including fragments that are thousands of nucleotides in length (it is noted that, for example, a typical Clostridium chromosome can contain 2 million nucleotides). Considering that S. pneumoniae includes the endonuclease recognition site GATC (as evidenced by claim 13), there would necessarily be naturally occurring Clostridium chromosome sequence that comprises at least one GATC sequence. Therefore, claim 8 does not add significantly more to judicial exception.
Regarding claim 9, limiting the fragment to between 50 and 50,000 base pairs does not add significantly to the product of nature as it is still a fragment of genomic DNA regardless of the size.
Regarding claims 10-12, requiring that the carrier is an aqueous solution wherein the carrier further comprises at least one of divalent cations, monovalent cations, dimethyl sulfoxide, dithiothreitol, and hexamine cobalt, wherein said cations are selected from the group consisting of Mg2+, Mn2+, Ca2+, Rb+, K+, does not add significantly more to the product of nature as it does not change the chemical structure of the DNA fragment.
Regarding claim 13, the requirement that the target organism is Clostridium difficile and the endonuclease recognition site is SEQ ID NO: 3 (the elected species), does not add significantly more to the judicial exception as the claim encompass a fragment of a naturally occurring Clostridium difficile DNA sequence.
Therefore, the claims are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon (product of nature), specifically a fragment of a genomic DNA sequence without significantly more.
Closest Prior Art
Donahue et al. (Molecular Microbiology (2000); of record – IDS citation), is considered the closest prior art. Donahue et al. teaches overcoming the restriction barrier to plasmid transformation of Helicobacter pylori, wherein plasmid DNA is methylated such that when it is transformed into H. pylori it is protected from nuclease degradation by the cell’s restriction-modification (R-M) system. Donahue et al. does not teach that the plasmid comprises a fragment of DNA exogenous to the targeted organism (H. pylori) wherein said DNA fragment has at least 50% sequence homology to a DNA sequence of said targeted organism (H. pylori), and wherein said fragment comprises no more than 5 unprotected specific endonuclease recognition sites of said targeted organism (H. pylori).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to J. E. Angell whose telephone number is (571)272-0756. The examiner can normally be reached Monday-Friday (8:30-5:00).
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J. E. Angell
Primary Examiner
Art Unit 1637
/J. E. ANGELL/Primary Examiner, Art Unit 1637