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 without traverse of group I, claims 1-19 in the reply filed 8/14/2025 is acknowledged.
Applicant's election with traverse of species of liver in the reply filed on 8/14/2025 is acknowledged. The traversal is on the ground(s) that there is not a serious search burden This is not found persuasive because searching liver samples will not inherently provide art on lung, spleen, brain, thymus, etc. However, the species election is withdrawn.
Claim 20 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invneiton, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 8/14/2025
Priority
The instant application was filed 09/23/2022 and claims priority from provisional application 63248205 , filed 09/24/2021.
Drawings
The drawings are objected to because Figure 1 provides a nucleotide sequences not identified by SEQ ID NO.. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
The application fails to comply with CFR 1.821(d), which states:
(d)Where the description or claims of a patent application discuss a sequence that is set forth in the “Sequence Listing” in accordance with paragraph (c) of this section, reference must be made to the sequence by use of the sequence identifier, preceded by “SEQ ID NO:” in the text of the description or claims, even if the sequence is also embedded in the text of the description or claims of the patent application.
For example, Figure 1, contains a nucleic acid sequence. Applicant is required to check the rest of the disclosure for any other nucleic acid or protein sequences and list them in a sequence listing and identify them with a proper SEQ ID NO.
The specification and sequence listing must be amended to bring it into sequence compliance. For any response to this office action to be fully compliant, the response has to bring the application in compliance with sequence rules.
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 1-19 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 recites, “mixing the tissue with a homogenization buffer composition to create a tissue homogenate.” The metes and bounds are unclear as the claim requires mixing, but does not require the sample is homogenized. Thus the metes and bounds are unclear what is required of tissue homogenate.
Claim 1 recites, “adding the tissue homogenate to a quantity of oligonucleotide-free plasma to create a tissue homogenate solution.” The metes and bounds are unclear of what is required of “oligonucleotide-free plasma .” Review and searching of the specification did not reveal a definition of oligonucleotide. The art recognizes most if not all blood, serum, or plasma contain nucleic acid or oligonucleotides. The metes and bounds are unclear what is required of oligonucleotide-free plasma.
Claim 1 recites, “ a concentration of the oligonucleotide, wherein the oligonucleotide is a toll-like receptor 9 agonist oligonucleotide having the structure: 5'-TCG AAC GTT CGA ACG TTC GAA CGT TCG AAT-3' (SEQ ID NO: 1).” However the claim previously recites, “adding a quantity of a reference standard oligonucleotide to the tissue homogenate solution.” Thus the metes and bounds of what is required of the oligonucleotide.
Claim 1 recites, “homogenate/plasma/standard.” The metes and bounds are unclear what is required or encompassed by the recitation with slashes.
Claim 1 recites, “phenol/chloroform/isoamyl alcohol.” The metes and bounds are unclear what is required or encompassed by the recitation with slashes as the recitation is not art accepted. The claim should be amended to clarify what is being required.
Claim 1 recites, “employing centrifugal force to separate a supernatant from the homogenate/plasma/standard solution.” The metes and bounds are unclear as this step is recited after, “adding a quantity of a phenol/chloroform/isoamyl alcohol to the homogenate/plasma/standard solution.” Thus it is unclear what is required, and how it relates to the preceding step as the recitation is not art accepted. The claim should be amended to clarify what is being required.
Claim 14 recites, “homogenate/plasma/standard.” The metes and bounds are unclear what is required or encompassed by the recitation with slashes as the recitation is not art accepted. The claim should be amended to clarify what is being required.
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.
Claim(s) 1-19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Dina (US Patent 9422564), Levers (Frontiers in Microbology (2015) pages 1-25), Cortese (Molecules 2020, 25, 3047; doi:10.3390/molecules25133047)
Dina teaches SEQ ID NO 172 which comprises claimed SEQ ID NO 1.
Dina teaches SEQ ID NO 172 is an immunomodulatory polynucleotide. Dina teaches treatment of individuals with immunomodulatory polynucleotide (column 57-58). Dina teaches SEQ ID NO 172 increases interferon alpha more than other oligonucleotides (column 72).
Dina does not specifically teach isolation of the oligonucleotide from tissue with ammonium acetate or use of a reference oligonucleotide..
However, Levers teaches isolation of nucleic acids from numerous sources including the use of ammonium acetate with phenol-chloroform-isoamyl alcohol. Levers teaches optimization of nucleic isolation.
Cortese provides review on how to compensate for matrix effects in drug testing by use of plasma. Cortese teaches the use of plasma and spike in controls.
MPEP 2144.05 II A States:
II. ROUTINE OPTIMIZATION
A. Optimization Within Prior Art Conditions or Through Routine Experimentation
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In reAller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)
The courts have haled that rearrangement of steps is obvious in the absence of unexpected results. Ex parte Rubin, 128 USPQ 440 (Bd. App. 1959) (Prior art reference disclosing a process of making a laminated sheet wherein a base sheet is first coated with a metallic film and thereafter impregnated with a thermosetting material was held to render prima facie obvious claims directed to a process of making a laminated sheet by reversing the order of the prior art process steps.). See also In re Burhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946) (selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results); In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930) (Selection of any order of mixing ingredients is prima facie obvious.).
Therefore it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims to detect ODN SEQ ID NO 172 of Dina, by nucleic acid isolation techniques of Levers including the use of ammonium acetate.in homogenization buffer The artisan would be motivated to determine the amount of ODN SEQ ID NO 172 of Dina in tissues in subjects treated by Dina methods. The artisan would have a reasonable expectation of success as the artisan is merely using known methods.
With regards to claims 2-5, MPEP 2144.05 II A States:
II. ROUTINE OPTIMIZATION
A. Optimization Within Prior Art Conditions or Through Routine Experimentation
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In reAller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)
Thus it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims to optimize the concentration and pH of ammonium acetate. The artisan would be motivated to optimize ammonium acetate concentration
With regards to claims 6-9, 13, 14provide ratio of grams of tissue to amount of homogenization buffer. One of skill in the art would recognize there and many variables such as tissue, homogenization method, surfactant, etc., to determine the ratio of buffer to tissue. Thus it would have been prima facie obvious to one of ordinary skill in the art depending on the tissue, surfactant, homogenization method, etc. to optimizes the buffer to tissue ratio. The artisan would have a reasonable expectation of success as the artisan is merely optimizing known methods.
With regards to claims 10-12, Levers teaches 0–4 μg mL−1. Thus it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims to optimize the concentration and proteinase K. The artisan would be motivated to optimize proteinase K concentration to maximize nucleic acids isolated. The artisan would have a reasonable expectation of success using known methods.
With regards to claims 15-16, Lever teaches Phenol-chloroform-isoamylalcohol (PCI; 25:24:1)(table 2).
With regards to claim 17, Cortese teaches HPLC-MS (page 2).
With regards to claims 18-19, Dina teaches, “ The LMSs can be targeted to any cell type toward which a therapeutic treatment is to be directed, e.g., a cell type which can modulate and/or participate in an immune response. Such target cells and organs include, but are not limited to, APCs, such as macrophages, dendritic cells and lymphocytes, lymphatic structures, such as lymph nodes and the spleen, and nonlymphatic structures, particularly those in which dendritic cells are found.” Thus it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims to isolate nucleic acids from brain, lung, lymphoid tissue, etc using proteinase K and ammonium acetate. The artisan would be motivate to determine where the oligonucleotide of Dina was taken up into tissue. The artisan would have reasonable expectation of success as the artisan is using known methods.
Summary
No claims are allowed.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEVEN C POHNERT PhD whose telephone number is (571)272-3803. The examiner can normally be reached Monday- Friday about 6:00 AM-5:00 PM, every second Friday off.
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/Steven Pohnert/ Primary Examiner, Art Unit 1683