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 the species of LRRK2 in the reply filed on 05/08/2026 is acknowledged. The elected species reads upon the LRRK2 protein and the pS935-LRRK2 and pS1292-LRRK2 sub-species. Applicant asserts at p. 6, 1st paragraph that claims 1, 2, 16, 17, 19-24, 26, 29, 32, 34, 36, 38, 40, 43, 46 and 52 will be under examination, however, claims 29, 32, 34, 36 and 38 read upon non-elected species. Therefore, claims 1, 2, 16, 17, 19-24, 26, 40, 43, 46 and 52 are under examination insomuch as they read upon the elected invention.
Priority
Acknowledgment is made of Applicant's claim for foreign priority based on an application filed in Greece on 10/30/2020. It is noted, however, that applicant has not filed a certified copy of the GR20200100660 application as required by 37 CFR 1.55.
Therefore, the priority date of the instant claims is deemed to be 10/29/2021.
Claim Objections
Claims 2, 17 and 19-21 are objected to because of the following informalities. The space between “neuro” and “degenerative” is not necessary. The term should be written “neurodegenerative” as it is in claim 1.
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, 2, 16, 17, 19-24, 26, 40, 43, 46 and 52 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exceptions without significantly more. The claims recite methods of making a clinical decision for an individual suspected of having, or at risk of progressing to a neurodegenerative disease or disorder comprising performing an assay on a biological sample obtained from the individual to determine a level, post-translational modification, or both of LRRK2 (the elected species) and making the clinical decision based on said level, post-translational modification, or both. The claims are directed to the statutory category of a process. See Step 1 of the Revised Guidelines.
The first step in determining whether a claim recites patent eligible subject matter is to consider whether the claims recite an abstract idea, law of nature or a natural phenomenon. See Prong One of Step 2A in the Revised Guidelines. As noted above, the claims are drawn to performing an assay on a biological sample to determine a level, post-translational modification, or both of LRRK2 and making the clinical decision based on the assay results. The claims also recite:
the clinical decision is determining at least one of a prognosis for the individual (claim 2);
determining the individual's responsiveness to a neurodegenerative disease or disorder therapy (claim 16);
determining a likelihood of an adverse response or beneficial response to the neurodegenerative disease or disorder therapy (claim 17);
modifying a neurodegenerative disease or disorder therapy (claim 19); and
monitoring effectiveness of the neurodegenerative disease or disorder therapy by monitoring for a change in the level, post- translational modification, or both of LRRK2 (claim 20).
Thus, the claims recite a series of diagnostic steps based upon the results of a biomarker assay. Dependent claims 22-24 recite the assay of claim 1 measures total protein, phosphorylated protein, or aggregated protein, wherein the aggregated protein is selected from the group consisting of amorphous aggregates, oligomers, fibrils, and combinations thereof and the level is a concentration or a ratio of phosphorylation to total protein. Therefore, the judicial exception is the relationship between total LRRK2, phosphorylated LRRK2 or aggregated LRRK2 and making clinical decisions based upon the results. The mental step of comparing biomarker levels is implicit in the claims and is similar to comparing information regarding a sample or test subject to a control or target data (see Univ. of Utah Research Found, v. Ambry Genetics Corp., 113 USPQ2d 1241 (Fed. Cir. 2014), or diagnosing an abnormal condition by performing clinical tests and thinking about the results (see In re Grams, 12 USPQ2d 1824 (Fed. Cir. 1989). The answer to Prong One of Step 2A is yes.
The second step in determining patent-eligibility of claimed subject matter is to consider whether the claims recite additional elements that integrate the judicial exception into a practical application. Claim 1 requires performing an assay on a biological sample obtained from an individual, which amounts to sample collection and performing assays. The judicial exception is not integrated into a practical application because sample collection and performing assays are merely the necessary data gathering required in order to perform the mental analysis steps of comparison and diagnosis/prognosis. Further, while claim 21 recites non-specific neurodegenerative disease/disorder therapies, it depends from claim 2, which states that the clinical decision is determining a neurodegenerative disease or disorder therapy, thus in the context of the claims, the therapies are part of a decision process that is the judicial exception.
The discovery of the relationship between biomarkers and a particular condition is not sufficient to integrate the judicial exception into a practical application. See MPEP 2106.04(I), which instructs:
The Supreme Court’s cited rationale for considering even “just discovered” judicial exceptions as exceptions stems from the concern that “without this exception, there would be considerable danger that the grant of patents would ‘tie up’ the use of such tools and thereby ‘inhibit future innovation premised upon them.’” Myriad, 569 U.S. at 589, 106 USPQ2d at 1978-79 (quoting Mayo, 566 U.S. at 86, 101 USPQ2d at 1971). See also Myriad, 569 U.S. at 591, 106 USPQ2d at 1979 (“Groundbreaking, innovative, or even brilliant discovery does not by itself satisfy the §101 inquiry.”). The Federal Circuit has also applied this principle, for example, when holding a concept of using advertising as an exchange or currency to be an abstract idea, despite the patentee’s arguments that the concept was “new”. Ultramercial, Inc. v. Hulu, LLC, 772 F.3d 709, 714-15, 112 USPQ2d 1750, 1753-54 (Fed. Cir. 2014). Cf. Synopsys, Inc. v. Mentor Graphics Corp., 839 F.3d 1138, 1151, 120 USPQ2d 1473, 1483 (Fed. Cir. 2016) (“a new abstract idea is still an abstract idea”) (emphasis in original).
Further, in explaining Prong Two of Step 2A, MPEP 2104.04(II)(A)(2) states patent “eligibility ‘cannot be furnished by the unpatentable law of nature (or natural phenomenon or abstract idea) itself’”. In summary, the judicial exception is not integrated into a practical application because the additional steps constitute mere data gathering. The answer to Prong Two of Step 2A is no.
The final step in determining whether the claims recite patent eligible subject matter is to consider whether the claims recite additional elements that amount to significantly more than the judicial exception. Dependent claims 43 and 46 recite common immunoassays for measuring LRRK2, however, these are well-understood, routine and conventional. For example, Taymans et al. (Biochemical Society Transactions (2017) 45 207-212) teach that immunoassays measuring both LRRK2 and its phosphorylated forms were well-known in the art (see p. 209, 2nd paragraph):
The detection of LRRK2 protein in tissue and biofluids has been facilitated by the development of rabbit and mouse monoclonal antibodies with specificity and sensitivity proven in immunohistochemistry and western blotting applications [29]. In addition to proteins detecting unmodified epitopes on LRRK2, several antibodies are also capable of phosphosite detection. Indeed, a key property of LRRK2 is that it is a highly phosphorylated protein, displaying at least 15 phosphorylation sites that can be categorized as autophosphorylation sites and sites phosphorylated by other kinases that we will call heterologous phosphorylation sites.
See also Kluss et al. (npj Parkinson’s Disease (2018) 4:13 ; doi:10.1038/s41531-018-0049-1), who teach measuring wild-type LRRK2 and S1292A-LRRK2 via western blots (see Figure 1 at p. 2). Finally, see Nichols (WO 2012159079), which teaches obtaining a biological sample from said subject, contacting said biological sample with a phosphorylation site-specific antibody that specifically binds LRRK2 when the LRRK2 is phosphorylated at residue Ser935, Ser955, and Ser973 in order to diagnose or prognose (see claim 17). For a claim reciting judicial exceptions to be eligible, the additional elements in the claim must “transform the nature of the claim” either at Prong Two or in Step 2B. In the instant case, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the steps are appending well-understood, routine and conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception (see MPEP 2106.05(d)).
Notice for all US Patent Applications filed on or after March 16, 2013: 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.
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.
Claims 1, 2, 16, 17, 19-22, 24, 26, 40, 43 and 52 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by West et al. (WO 2014059052—on IDS filed 07/28/2023). The claims of West et al. recite a method of diagnosing Parkinson's disease (PD) or parkinsonism or having an increased likelihood of having or developing PD or parkinsonism in a human subject, comprising obtaining a sample from said subject, detecting the amount of or activity of LRRK2 protein in the sample; and comparing the amount of or activity of LRRK2 protein in the sample from the subject to the amount of or activity of LRRK2 protein in a sample of a control, wherein an increase in the amount of or activity of LRRK2 protein in the sample as compared to the control diagnoses PD or parkinsonism in the subject, wherein detection of LRRK2 protein is carried out by immunohistochemistry, immunofluorescence or western blotting (see claims 1-12), thereby meeting the limitations of instant claims 1, 22, 24, 26, 43 and 52.
West et al. also teach a method of identifying a human subject as a suitable candidate for treatment that decreases the amount of LRRK2 protein and/or inhibits or reduces LRRK2 protein activity in a subject or determining the efficacy of a treatment for PD, comprising obtaining a sample, detecting the amount of or activity of LRRK2 protein in the sample and comparing the amount of or activity of LRRK2 protein in the sample from the subject to the amount of or activity of LRRK2 protein in a sample of a control, wherein an increase in the amount of or activity of LRRK2 protein as compared to a control indicates that the subject is a suitable candidate for treatment that decreases the amount of LRRK2 protein and/or inhibits or reduces LRRK2 protein activity and further comprises administering a treatment that decreases the amount of LRRK2 protein and/or inhibits LRRK2 activity in the subject, or wherein a decrease in the amount or activity of LRRK2 protein measured after the treatment as compared to before the treatment indicates efficacy of the treatment for PD or parkinsonism and wherein the treatment is a tyrosine kinase inhibitor or sunitinib (see claims 13-24), thereby also meeting the limitations of instant claims 16, 17, 19 and 20.
In addition to measuring via immunohistochemistry, immunofluorescence and western blotting, West et al. contemplate ELISAs (see claims 10-11; p. 18, lines 26-28). Further, West teaches measuring the level of pSer935-LRRK2 (see paragraph bridging pages 26-27; p. 28, lines 23-30). Finally, West et al. also teach that PD diagnosis can be made on the bases of p1292 LRRK2 and/or total LRRK2 protein levels as well as modifying therapy based on the results of the testing (see p. 14, lines 19-24; p. 15, lines 1-10), thus teaching additional limitations in instant claims 19, 24 and 40. In summary, West et al. teach the limitations of claims 1, 2, 16, 17, 19-22, 24, 26, 40, 43 and 52.
Claim Rejections - 35 USC § 103
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.
Claims 1, 2, 16, 17, 19-24, 26, 40, 43, 46 and 52 are rejected under 35 U.S.C. 103 as being unpatentable over West et al. (WO 2014059052—on IDS filed 07/28/2023) in view of Nichols (WO 2012159079) and Delbroek et al. (2013 J. Pharm. Biomed. Anal. 76, 49–58. doi: 10.1016/j.jpba. 2012.12.002). The first factor to consider when making a rejection under 35 U.S.C. 103(a) is to determine the scope and contents of the prior art. The claims of West et al. recite a method of diagnosing Parkinson's disease (PD) or parkinsonism or having an increased likelihood of having or developing PD or parkinsonism in a human subject, comprising obtaining a sample from said subject, detecting the amount of or activity of LRRK2 protein in the sample; and comparing the amount of or activity of LRRK2 protein in the sample from the subject to the amount of or activity of LRRK2 protein in a sample of a control, wherein an increase in the amount of or activity of LRRK2 protein in the sample as compared to the control diagnoses PD or parkinsonism in the subject, wherein detection of LRRK2 protein is carried out by immunohistochemistry, immunofluorescence or western blotting (see claims 1-12), thereby meeting the limitations of instant claims 1, 22, 24, 26, 43 and 52.
West et al. also teach a method of identifying a human subject as a suitable candidate for treatment that decreases the amount of LRRK2 protein and/or inhibits or reduces LRRK2 protein activity in a subject or determining the efficacy of a treatment for PD, comprising obtaining a sample, detecting the amount of or activity of LRRK2 protein in the sample and comparing the amount of or activity of LRRK2 protein in the sample from the subject to the amount of or activity of LRRK2 protein in a sample of a control, wherein an increase in the amount of or activity of LRRK2 protein as compared to a control indicates that the subject is a suitable candidate for treatment that decreases the amount of LRRK2 protein and/or inhibits or reduces LRRK2 protein activity and further comprises administering a treatment that decreases the amount of LRRK2 protein and/or inhibits LRRK2 activity in the subject, or wherein a decrease in the amount or activity of LRRK2 protein measured after the treatment as compared to before the treatment indicates efficacy of the treatment for PD or parkinsonism and wherein the treatment is a tyrosine kinase inhibitor or sunitinib (see claims 13-24), thereby also meeting the limitations of instant claims 16, 17, 19 and 20.
In addition to measuring via immunohistochemistry, immunofluorescence and western blotting, West et al. contemplate ELISAs (see claims 10-11; p. 18, lines 26-28). Further, West teaches measuring the level of pSer935-LRRK2 (see paragraph bridging pages 26-27; p. 28, lines 23-30). Finally, West et al. also teach that PD diagnosis can be made on the bases of p1292 LRRK2 and/or total LRRK2 protein levels as well as modifying therapy based on the results of the testing (see p. 14, lines 19-24; p. 15, lines 1-10), thus teaching additional limitations in instant claims 19, 24 and 40. In summary, West et al. teach the limitations of claims 1, 2, 16, 17, 19-22, 24, 26, 40, 43 and 52. The second factor to consider is to ascertain the differences between the prior art and the instant claims. West et al. do not teach measuring aggregated protein as recited in claim 23 or an ELISA comprising antibodies to at least two proteins selected from, total LRRK2, pS935-LRRK2 and pS1292-LRRK2 as recited in claim 43.
Regarding protein measuring aggregation, the WO document by Nichols describes assays in which aggregates are measured (see claim 13; p. 28, paragraph [00131]; pages 31-32, paragraphs [00141]-[00145]; pages 35-36 paragraph [00160]). Nichols also teach methods of diagnosing, theranosing, prognosing, or determining treatment efficacy for a subject suffering from a synucleopathy involving Lewy body neurodegeneration in PD, comprising obtaining a biological sample from said subject, contacting said biological sample with a phosphorylation site-specific antibody that specifically binds LRRK2 only when the LRRK2 is phosphorylated at a residue selected from the group consisting of: Ser910, Ser935, Ser955, and Ser973 and detecting binding of said phosphorylation site-specific antibody to LRRK2, thereby diagnosing, theranosing, prognosing, or determining treatment efficacy for said subject (see claims 17 and 18).
It would have been obvious to the person of ordinary skill in the art at the time of the filing of the invention to modify the teachings of West et al. by measuring protein aggregation, as taught in Nichols because protein aggregation is a common occurrence in PD, which is characterized therein as “a distinct protein aggregation disorder affecting specific subpopulations of neurons” (see p. 4, paragraph [0026] of Nichols). The person of ordinary skill in the art would have been motivated to measure protein aggregates because PD is protein aggregation disorder and because Nichols suggests several methods for measuring aggregation (claim 13; p. 28, paragraph [00131]; pages 31-32, paragraphs [00141]-[00145]; pages 35-36 paragraph [00160]). Since PD was known to be a protein aggregation disorder and assays for measuring aggregation were well-known in the art, the person of ordinary skill in the art could have reasonably expected success.
Regarding ELISA assays, Nichols also teaches “phospho-specific antibodies” for use in “conventional immunoassays include, without limitation, an ELISA, an RIA, FACS, tissue immunohistochemistry, Western blot or immunoprecipitation assays” (see paragraph [0058]). Further, Delbroek et al. teach an ELISA assay in which plates “were coated overnight at 4 ◦C with capturing antibody (anti-GFP or anti-LRRK2)” followed by the addition of primary antibodies and “colorimetric (A450 nm) detection of HRP activity with TMB as a substrate or with fluorescent detection via Quantablue methodology according to the manufacturer’s instructions” (see paragraph bridging left and right columns at p. 51). In addition, Delbroek et al. teach the development of an assay that measures anti-pS935 antibodies with “a sandwich ELISA where an anti-GFP antibody is used to capture the overexpressed GFP-LRRK2 followed by detection of total LRRK2 and S935/S910 phosphorylated LRRK2 with the antibodies mentioned above” (paragraph bridging pages 51 and 52). Finally, Delbroek et al. teach measuring a ratio of pS935LRRK2 to total LRRK2 (see p. 52, right column, 1st paragraph).
It would have been obvious to the person of ordinary skill in the art at the time of the filing of the invention to modify the teachings of West et al. by utilizing an ELISA comprising at least two antibodies, as taught in Nichols and Delbroek and colleagues because ELISA assays are “straightforward” (see Delbroek et al. at p. 52, left column, 1st paragraph). The person of ordinary skill in the art would have been motivated to do so because Delbroek et al. teach “the pS935 ELISA might also be useful to determine pharmacological inhibition of LRRK2 in human blood” and “the ELISA platform makes it useful for high throughput purposes” (see p. 55, left column). Furthermore, the person of ordinary skill in the art could have reasonably expected success because Delbroek et al. teach their “data clearly show that the assay is a good tool for measuring the effect of LRRK2 kinase inhibitors, both in rodent and human samples” (see p. 57, right column, 3rd paragraph).
Thus, the claims do not contribute anything non-obvious over the prior art.
Claim Rejections - 35 USC § 112(a)
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, 2, 16, 17, 19-24, 26, 40, 43, 46 and 52 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 the claimed methods in which the ratio of pS935 to total LRRK2 is increased in idiopathic Parkinson’s Disease (iPD) compared to control, wherein iPD patients are treated with an LRRK2 small molecule inhibitor or an anti-LRRK2 antibody; or alternatively, methods as set forth in the prior art teachings, does not reasonably provide enablement for the claims as broadly recited. 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.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.” (See In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 Fed. Cir. 1988). These factors include, but are not limited to: (a) the breadth of the claims; (b) the nature of the invention; (c) the state of the prior art; (d) the level of one of ordinary skill; (e) the level of predictability in the art; (f) the amount of direction provided by the inventor; (g) the existence of working examples; and (h) the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The claims are broad with respect to the patient population and contemplated therapies. Further, the claimed methods do not recite whether LRRK2 levels are up- or down-regulated. The instant specification discloses that the ratio of pS935-LRRK2 to total LRRK2 levels are significantly higher in PBMCs of iPD patients compared to healthy controls (see paragraph [0080]; Fig. 3D). Further, the prior art teaches that LRRK2 levels are higher in PD patients than controls; for instance, see the claims of West et al. (WO 2014059052—on IDS filed 07/28/2023). Neither the specification nor the prior art teaches or suggests, however, that LRRK2 levels or post-translational modifications can be used to make clinical decisions for the patient population as broadly claimed.
The specification and claims are broad with respect to the encompassed neurodegenerative disease or disorder therapy, which may be a small molecule, an immunotherapy, a gene therapy, a non-medication-based therapy, an antibody, an antigen binding fragment, an RNA interfering agent (RNAi), a small interfering RNA (siRNA), a short hairpin RNA (shRNA), a microRNA (miRNA), an antisense oligonucleotide, a peptide or a peptidomimetic. The claims and specification do not provide any structural or functional description. The art teaches that progress is being made in developing small molecule LRRK2 inhibitors for treating PD. See, for instance, Hu et al. (European Journal of Medicinal Chemistry 256 (2023) 115475) and Henderson et al. (J. Med. Chem. 2015, 58, 419-432). In addition, Davies et al. (Biochem. J. (2013) 453, 101-113) reviews anti-LRRK2 monoclonal antibodies. Nevertheless, there is no guidance in the specification or the art for gene-therapy based treatments, particularly in light of the definition of treating in the instant specification, that encompasses prophylaxis and prevention (see paragraph [0022]).
Gene therapy with antisense, siRNA and shRNA is complex. For instance, the extensive review by Hu et al. (Signal Transduction and Targeted Therapy (2020) 5:101) provides background on the current state of the art of siRNA therapy and outlines the challenges thereto (p. 2, left column, 2nd paragraph):
Although siRNA holds promising prospects in drug development, several intracellular and extracellular barriers limit its extensive clinical application. Naked and unmodified siRNA possesses some disadvantages, such as (1) unsatisfactory stability and poor pharmacokinetic behavior and (2) the possible induction of off-target effects. The phosphodiester bond of siRNA is vulnerable to RNases and phosphatases. Once it is systematically administered into circulation, endonucleases or exonucleases throughout the body will quickly degrade siRNA into fragments, thus preventing the accumulation of intact therapeutic siRNA in the intended tissue. In theory, siRNA only functions when its antisense strand is completely base-paired to the target mRNA. However, a few mismatches are tolerated by the RNA-induced silencing complex (RISC), which may lead to undesired silencing of those genes with a few nucleotide mismatches.
Hu et al. review the techniques undertaken to deal with the challenges of siRNA therapy, which serve to underscore the complexity of the field. For instance, base modification is a promising technique, but one that is “basically at the stage of research and development” (see discussion under “Base modification in the paragraphs bridging the left and right columns of p. 6). Regarding siRNA delivery, Hu et al. teach:
Only 1–2% of internalized LNP [lipid nanoparticle]-loaded siRNAs were released into the cytoplasm, and this only occurred within a limited time frame after internalization. Hence, further understanding the escape mechanism and how to enhance the escape efficiency is of great importance for siRNA drug development (p. 11, left column, 1st paragraph). Citations omitted by examiner.
In spite of progress made in the field of siRNA drug development and delivery, Hu et al. underscore the complexity of a field that is still in its developmental stage.
Relevant literature teaches despite having made strides over the past 40 years, gene therapy remains unpredictable (see Antoine Gardin and Giuseppe Ronzitti, Archives de Pédiatrie 30 (2023) 8S46–8S52—hereafter “Gardin”). Gardin teaches that while methods of using adeno-associated viral (AAV) vectors for transducing DNA have improved, particularly in the treatment of the liver, central nervous system, muscles, eye and bone marrow, significant challenges remain (see p. 8S46, left column, 1st paragraph). For instance, besides immunogenicity, challenges include non-target organ effects, the neutralizing effect of autoantibodies and loss of long-term correction (see p. 8S48, left column, 2nd paragraph; paragraph bridging pages 8S48-8S49; p. 8S49, under “3”). In view of the teachings of the relevant art, the ability to treat neurodegenerative disorders using RNA- or DNA-based therapies was not readily available in the relevant art at the time of filing of the instant application, and the limited teachings of the instant application do not overcome these shortcomings.
Due to the large quantity of experimentation necessary to develop the diagnostic methods for all of the encompassed neurodegenerative diseases/disorders as well gene therapy methods capable of treating these diseases/disorders, the lack of direction/guidance presented in the specification regarding and the absence of working examples directed to the same, the complex nature of the invention (diagnosis and treatment of neurodegenerative diseases), and the breadth of the claims which fail to recite limitations on the patient population, therapies or how to make the clinical decisions (e.g., are proteins up- or down-regulated), undue experimentation would be required of the skilled artisan to make and/or use the claimed invention in its full scope.
Conclusion
No claim is allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Bustos et al. (WO 2012075046) teach methods for identifying a patient or subject having Parkinson's disease or at risk of developing Parkinson's disease and for predicting the sensitivity of a subject to a LRRK2 modulator the method comprising obtaining or acquiring a sample from the subject, determining the level of S1292 autophosphorylation in said subject, wherein an elevated level correlates with having Parkinson's disease or risk of developing Parkinson's disease, and further comprising administering a LRRK2 modulator to the subject, wherein said modulator may be a small molecule (see claims 1-8, paragraphs [0075]; [0113]). In addition, Rideout et al. (Front. Neurosci. 14:865. doi: 10.3389/fnins.2020.00865, published August 18 2020) review past and current platforms and future directions for detecting LRRK2 levels, phosphorylation, autophosphorylation and activity.
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/CHRISTINA M BORGEEST/Primary Examiner, Art Unit 1675
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