DETAILED ACTION
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. Applicant’s Request for Continued Examination, Amendment and Arguments/Remarks received on 13 March 2026 have been entered. Claims 1-7 and 11-22 were previously pending in the application. No claims have been newly cancelled, and no new claims have been added by Applicant. Claims 1-7 and 11-22 are currently pending in the application. Claims 1, 11, 13, 15, and 16 are independent claims.
The election of Group II, drawn to a method for the detection of a target nucleic acid, remains in effect in the instant application.
The following election of species remains in effect in the instant application:
1) Polycationic particle: a. a polycationic polysaccharide iii. chitosan; and
3) Molar ratio: k. 1:1.
Claims 1-7, 11-12, 15-16, and 18-20 remain withdrawn from consideration as being directed to a nonelected invention, there being no allowable generic or linking claim.
Claims 13-14, 17, and 21-22 are currently pending and under examination in the instant application. An action on the merits follows.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Priority
The present application is a 35 U.S.C. 371 national stage filing of International Application No. PCT/EP2020/052764, filed 04 February 2020, which claims priority to EPO 19155556.4, filed 05 February 2019. Filing of a certified copy of the EPO 19155556.4, filed 05 February 2019 is acknowledged.
Thus, the earliest possible priority for the instant application is 05 February 2019.
Information Disclosure Statement
The information disclosure statement filed 30 October 2025 has been considered by the Examiner. Examiner notes the filing of IDS Size Fee assertions for the IDS filed 30 October 2025, as required under 37 CFR 1.98, indicating that no IDS size fee is required under 37 CFR 1.17(v) at this time.
Drawings
The drawings are objected to because the figure label for Fig. 3 and Fig. 5 is not oriented in the same direction as the figure. See 37 CFR 1.84 (p)(1). Appropriate correction is required.
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.
37 CFR 1.121(c)
The claim amendments filed 02 January 2026 is objected to under 37 CFR 1.121(c) because Applicant’s claim listing is not in compliance with 37 CFR 1.121(c) which states that the claim listing must provide the status of all claims, that all claims being currently amended in an amendment paper shall be presented in the claim listing, indicate a status of "currently amended," and be submitted with markings to indicate the changes that have been made relative to the immediate prior version of the claims. The text of any added subject matter must be shown by underlining the added text. The text of any deleted matter must be shown by strike-through except that double brackets placed before and after the deleted characters may be used to show deletion of five or fewer consecutive characters. The text of any deleted subject matter must be shown by being placed within double brackets if strike-through cannot be easily perceived.
Specifically, claim 13 is marked “Currently amended” and comprises some markings indicating insertions and deletions from the previous version. However, amended claim 13 omits the deleted text “the polycationic particle” from lines 4-5 of the prior version of the claim (i.e., between “and wherein” and “the molar ratio” in line 4 of the current version of the claim filed 13 March 2026) which should be present and marked with a strikethrough. Additionally, amended claim 13 comprising new text “the molar” in line 4 of the current version of the claim filed 13 March 2026 which has not been designated as in insertion by underlining.
In the interests of compact prosecution, the claim listing has been entered. However, future claim listings must include the correct status of all claims, along with the appropriate mark-ups for changes to the claims, in order for the claim listing to meet the requirements for entry under 37 CFR 1.121(c) or a Notice of Non-Compliant Amendment will be mailed to applicant.
Claim Rejections - 35 USC § 112(b)
The rejection of amended and previously presented claims 13-14, 17, and 21-22 under 35 U.S.C. 112(b) as failing to particularly point out and distinctly claim the subject matter which the inventor(s) regards as the invention for multiple issues of indefiniteness is maintained.
Applicant amended the claims to partially address the issues of indefiniteness identified in the prior action. However, the following issues of indefiniteness have not been fully overcome.
Applicant amended independent claim 13 to recite, “and wherein the molar ratio of the control nucleic acid to polycationic particle in the complex corresponds to the molar ratio of the target nucleic acid present in a biological particle to the biological particle” in lines 4-7, which improves the clarity of the claim.
However, the phrase is still indefinite in that Applicant has not defined the metric for determining a molar ratio of the polycationic particle to the control nucleic acid, particularly in light of the fact that cationic polymers have diverse molecule sizes with differing numbers of monomers per polymer. Further, it is unclear whether the molar amount of polycationic particles used for the ratio is the mols of individual polycationic molecules or the mols of particles formed by association of multiple polycationic molecules. Additionally, it is unclear whether Applicant intends to treat a double stranded target as a single molecule or as two molecules given that the two strands are not covalently attached to each other. Nor is it clear whether a duplication of the target nucleic acid sequence would amount to a doubling of the molar ratio if the duplicated sequences were covalently attached to each other. Further, it is unclear whether Applicant intends to treat a whole biological particle (e.g., a cell or a virus) as a single entity for purposes or a molar ratio calculation (e.g., [mols of target nucleic acid]:[mols of biological particle/cells/virus]) or whether applicant intends to use the total of all molecules and/or atoms within the biological particle/cell/virus to calculate the number of mols for the biological particle. The instant specification has not provided any metric or definition for determining the intended calculation.
Additionally, it is unclear whether the biological particle is meant to be present in the sample or whether the biological particle encompasses any biological particle in which the target nucleic acid may be present at any time or under any conditions. Similarly, it is unclear whether the target nucleic acid is required to be present in a biological particle within the sample or whether “the molar ratio of the target present in a biological particle to the biological particle” is merely referencing what the molar ratio when the nucleic acid is present in a biological particle without requiring the presence of the target nucleic acid within the sample to be present within a biological particle.
Additionally, amended claim 13 newly recites “corresponds to” in place of “comparable to”, which is still indefinite because it is unclear what scope of molar ratios would “correspond to” another molar ratio. For example, it is unclear whether the molar ratios must be exactly equal to each other or within some percentage range of each other.
Also, recitation of “the molar ratio” in lines 4 and 6 still lack antecedent basis in the claim.
As such, the metes and bounds of the claim still cannot be determined.
Applicant argues that:
One skilled in the art would understand the term “molar ratio” such that neither “molar ratio” nor methods of determining molar ratio need to be specified in the claim;
The term “biological particle” is readily understood by one of skill in the art such that it would be readily understood by one of skill in the art to depend on the specific target nucleic acid; for example, if the target nucleic acid is a viral nucleic acid one of skill in the art would understand that the biological particle would be a virus.
However, this is not agreed.
Regarding Applicant’s argument 1), the issue of indefiniteness in the claim is not an issue with the definition of the term “molar ratio” itself. The indefiniteness at issue relates to the metes and bounds of what is being compared to produce the molar ratio. For example, the art at the time of filing uses a variety of methods for quantifying a polycationic particle, such as using the number average molar mass of the polymer, the weight average molar mass of the polymer, the viscosity average molar mass of the polymer, the number of monomers within the polymeric particle, and/or using the number of charged groups within the polycationic particle. Further, it is unclear whether “polycationic particle” encompasses a single molecule of a polycationic molecule or a complex of polycationic molecules, such as a liposome or a nanoparticle.
Regarding Applicant’s argument 2), note that the issues of indefiniteness do not stem from a lack of understanding what may be encompassed by the broad term “biological particle”, but what specifically is encompassed by the term as used within the claim. More specifically, it is unclear whether Applicant is referring to moles of biological particles (e.g., number of viruses in the provided example) or whether Applicant is referring to the molecules and/or atoms comprised within the biological particle. As such, it is unclear whether Applicant intends the claim to encompass a molar ratio of the number of target nucleic acid molecules present in a biological particle within a sample to the number of biological particles within a sample, to the number of molecules within a single biological particle, to the number of molecules within all the biological particles in a sample, to the number of atoms within a single biological particle, and/or to the number of atoms within all the biological particles in a sample.
Additionally, given the example provided by Applicant, it would not necessarily be readily apparent that the viruses themselves would be the biological particle being considered for a viral nucleic acid if that virus/ viral nucleic acid were comprised within a host cell or organism. As such, the claim is interpreted to encompass any biological particle (e.g., cell, virus, organelle, complex) which comprises any target nucleic acid sequence. Further, as the claim is written, it is unclear whether the biological particle is meant to be present in the sample or whether the biological particle encompasses any biological particle in which the target nucleic acid may be present at any time or under any conditions. For example, given Applicant’s example, if the target nucleic acid is a viral nucleic acid and the corresponding biological particle is a virus, it is unclear whether the virus itself must be present in the sample comprising the target nucleic acid or whether any composition comprising the target nucleic acid with or without viral particles would be encompassed by the claim.
Therefore, Applicant’s arguments do not overcome the indefiniteness rejection under 112(b).
The rejection of amended claim 21 under 35 U.S.C. 112(b) as failing to particularly point out and distinctly claim the subject matter which the inventor(s) regards as the invention for reciting “wherein the method for the detection of the target nucleic acid is a diagnostic or a forensic method or wherein the method comprises a step of a diagnostic or a forensic method or wherein the method is a step of a diagnostic or a forensic method”, is withdrawn in view of Applicant’s amendment to claim 21 to recite, “diagnostic method”.
Claim interpretation
As indicated in the prior action, the term “molar ratio” of the control nucleic acid to polycationic particle in claim 13 has been interpreted to encompass a molar ratio of the phosphate groups in the control nucleic acid to the amine groups (or other + charged groups) in the polycationic particle (e.g., chitosan), also known in the inverse as the N/P ratio; the molar ratio of the molecules of the control nucleic acid to the molecules of the polycationic polymer; and/or the molar ratio of the number of molecules of the control nucleic acid to the number of formed particles.
As indicated in the prior action, the term “sample” in claim 13 has been interpreted to refer to any composition having any components.
Claim Rejections - 35 USC § 103
The rejection of amended and previously presented claims 13-14, 17, and 21-22 under 35 U.S.C. 103 as being unpatentable over Etchebarne et al. [2017, Frontiers in Microbiology, Vol. 8, 2211, 1-13, cited in a prior action]; in view of Cheung [US20110171314A1, published 14 July 2011, cited in a prior action]; Gaspar et al. [2011, Nanotechnology, Vol. 22, 015101, 1-13, cited in a prior action]; Danielsen et al. [2004, Biomacromolecules, 5(3), 928-936]; and Hildenbrand et al. [2011, Journal of Bacteriology, 193(3), 734-743], is maintained. Applicant's amendments to the claims and arguments have been fully considered but have not been found persuasive in overcoming the rejection for reasons of record as discussed in detail below.
Applicant amended the claims to partially address issues of indefiniteness identified in the prior action. However, the amendments to the claims do not alter the scope of the claims sufficiently to overcome the finding of obviousness, and as such, Applicant’s amendments do not overcome a finding of obviousness under 35 U.S.C. 103 over Etchebarne, Cheung, Gaspar, Danielsen, and Hildenbrand, as discussed in the prior action.
Applicant argues that none of Gaspar, Danielsen, and Hildenbrand cure the deficiencies of Etchebarne in not teaching the delivery of a control nucleic acid to a sample in a complex comprising at least one polycationic particle (e.g., the elected chitosan) and the control nucleic acid, wherein the molar ratio of the control nucleic acid to polycationic particle in the complex corresponds to the molar ratio of the target nucleic acid present in a biological particle to the biological particle, in that:
Gaspar discloses the protection of DNA from nucleolytic degradation by encapsulation within nanocapsules with no reference to the claimed comparability of the two molar ratios;
Danielsen analyzes structural properties of condensation complexes, but the claimed complex according to the present invention is functionally defined in the context of a diagnostic method and not as a mere condensation product;
Hildenbrand describes biological ploidy ratios, which relates to an inherent property of natural organisms, not to the technical design of an artificially produced complex; and
One of skill in the art would have no reason to establish any functional relationship between the variables of a structural relationship within a synthetic complex taught by Danielsen with a biological property of natural organisms as described by Hildenbrand, nor any reason to specifically align these ratios with each other.
However, this is not agreed.
In response to Applicant’s arguments against the references individually, it is noted that the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Further, the Examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In addition, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Specifically, regarding Applicant’s argument 1), as discussed in the prior action, Gaspar was cited for teaching that the development of nanocapsules that are stable in the extracellular environment is essential for the protection of nucleic acids, and that serum nucleases are a major concern that affects delivered DNA stability [column 18 ¶ 2-column 19 ¶ 1]. Gaspar further teaches that encapsidation of DNA within nanocapsules comprising chitosan protects DNA from degradation by incubation with DNase I and from degradation by incubation in serum-supplemented media [column 19 ¶ 1-column 20 ¶ 2, Figures 10-11]. Therefore, an ordinarily skilled artisan would have been motivated to utilize a chitosan nanocapsule to encapsidate a nucleic acid to be delivered to samples (potentially) comprising nucleases, such as samples comprising serum or other nuclease-comprising biological specimens, to protect the nucleic acid from degradation.
Accordingly, Gaspar provides the teachings and motivations for complexing a nucleic acid, such as the control nucleic acid of Etchebarne, with the elected polycationic particle comprising chitosan.
Regarding Applicant’s argument 2), as discussed in the prior action, Danielsen was cited for teaching the inherent properties of chitosan-DNA particles which form from complexing DNA and chitosan, wherein the chitosan-DNA particles consist of one or a few DNA molecules [column 13 ¶ 2], which is consistent with prior teachings that most condensed DNA complexes contain a single DNA molecule, whereas a few complexes contain two or three DNA molecules [column 13 ¶ 3- column 14 ¶ 1]. Therefore, Danielsen teaches that polycationic chitosan particles complexed with nucleic acids form such that the molar ratio of the control nucleic acid to polycationic chitosan particle are present in the complex in the elected molar ratio of 1:1.
Accordingly, Danielsen provides the teachings that a nucleic acid-chitosan particle complex forms in such a way so as to inherently produce a 1:1 molar ratio of nucleic acid to chitosan particle, at least for nucleic acids that are in the range of the nucleic acids used by Danielsen (i.e., plasmids of about 4.3 kbp or linear DNA of about 2 kbp) [column 3 ¶ 3] or larger, in that Danielsen teaches that, based on their data with DNA molecules of 4.3kbp and 2 kbp, multiple DNA molecules are not necessarily required to achieve condensation when the DNA molecule is shorter than 40 kpb [column 14 ¶ 1]. Note that the purified control DNA used by Etchebarne are genomic DNA molecules isolated from a variety of bacteria, including E. coli, which Hildenbrand teaches has a genome size of 4.6 Mbp [column 8 ¶ 1]. As such, the genomic DNA molecules used as control nucleic acid molecules by Etchebarne are greater than about 2 kpb [Tables 1A, 1B], and so the control nucleic acids of Etchebarne fall within the range of DNA sizes which Danielsen teaches form 1:1 ratios when complexed with chitosan particle. Further, an ordinarily skilled artisan at the time of filing the instant application would expect to achieve a ratio of 1:1 DNA: chitosan particles given the teachings of Danielsen.
Reliance upon inherency is not improper even though rejection is based on Section 103 instead of Section 102. In re Skoner, et al. 186 USPQ 80 (CCPA). As stated in MPEP 2112, The express, implicit, and inherent disclosures of a prior art reference may be relied upon in the rejection of claims under 35 U.S.C. 102 or 103. "The inherent teaching of a prior art reference, a question of fact, arises both in the context of anticipation and obviousness." In re Napier, 55 F.3d 610, 613, 34 USPQ2d 1782, 1784 (Fed. Cir. 1995). See also In re Grasselli, 713 F.2d 731,739, 218 USPQ 769, 775 (Fed. Cir. 1983).
Further, Applicant is reminded that 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 (i.e., chitosan particle) is capable of performing the intended use (i.e., complexing with a control nucleic acid and being added to a sample), then it meets the claim. The teachings of Danielsen are teachings of the structure of a chitosan-nucleic acid complex and are not restricted to specific intended uses of the complex.
Regarding Applicant’s argument 3), as discussed in the prior action, Hildebrand was cited for teaching a variety of prokaryotic organisms, including E.coli and others detected by Etchebarne, which comprise monoploid genomes, thereby teaching that a 1:1 ratio exists between a target nucleic acid present in a bacterial or archaeal cell and the bacterial or archaeal cells themselves. The inherent property of natural organisms is in fact relevant to the design of a method for detecting a target nucleic acid, such as a bacterial genome, in a sample, such as a biological blood or urine sample, for diagnostic purposes to indicate the presence of the bacterial species within the sample. Specifically, the inherent property of monoploidy in such natural organisms is highly relevant to the claimed method which recites “the molar ratio of the target nucleic acid present in a biological particle to the biological particle” (claim 13), “wherein the biological particle is a virus or cell” (claim 22).
Regarding Applicant’s argument 4), as discussed above and in the prior action, the motivation to combine a DNA-chitosan particle complex with the delivery of a control nucleic acid of Etchebarne is provided by the teachings of Gaspar. Further, the teachings of Danielsen relate to the production of DNA-chitosan complexes for the protection of DNA from degradation, which supports the motivated provided by Danielsen for complexing DNA with chitosan particles. Also, Hildebrand teaches properties of microorganisms, such E. coli and many other of the microorganisms taught by Etchebarne as being relevant for clinical diagnostic detection. Accordingly, the disclosures of Danielsen and Hildebrand do not represent irrelevant disclosures.
Additionally, Danielsen teaches the inherent properties of molar ratios for a 2kbp+ DNA molecule: chitosan particle in complex under varied conditions and Hildenbrand teachings the inherent properties of molar ratios for a target nucleic acid: biological particle within the biological particle. As such, the molar ratio of 1:1 (as elected) for the DNA: chitosan particles and target: biological particle are inherent to the combination of Etchebarne and Gaspar without any particular motivations to produce such ratios or align such ratios. Alternatively, as discussed above, an ordinarily skilled artisan at the time of filing the instant application would expect to achieve a ratio of 1:1 DNA: chitosan particle when formulating the complex with prokaryotic genomic DNA given the teachings of Danielsen.
Therefore, Applicant’s arguments do not overcome a finding of obviousness under 35 U.S.C. 103 over Etchebarne, Cheung, Gaspar, Danielsen, and Hildenbrand, and the rejection is maintained.
Conclusion
No claim is allowed.
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DR. KATIE L. PENNINGTON
Examiner
Art Unit 1634
/KATIE L PENNINGTON/Examiner, Art Unit 1634
Dr. A.M.S. Wehbé
/ANNE MARIE S WEHBE/Primary Examiner, Art Unit 1634
Prosecution Insights