DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This application is the national stage of PCT/US2021/056443, filed 25 October 2021, claiming prior to US provisional application 63/105,645, filed 26 October 2020. The International Search Report and Written Opinion issued in the PCT application have been received and reviewed.
Election/Restrictions
Applicant’s election of rs10784722 for (a), and “Formula (III)” having a 6-membered heteroaryl at Y, an aryl at R21, and a C2-8 heterocycloalkyl at R22 for (b), in the reply filed on 26 June 2026 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 “1-4, 6-11, 13, 14, 16-19, 20, and 21” were identified as readable on the elected species, however it is noted that claim 20 (like claims 5 and 12) is directed to non-elected species. Accordingly, claims 1-4, 6-11, 13-14, 16-19, and 21 are under consideration as directed to the elected species. It is noted that the prior art was not found to apply against the elected SNP rs10784722; accordingly, search and examination was extended to a different species of SNP (see the prior art rejection below). Please also note the improper Markush group rejection below (which relates to the species of (b)).
Claims 5, 12, and 20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 26 June 2026.
Claim Rejections – Improper Markush Grouping
Claims 6, 13, and 21 are rejected on the basis that the claims contain an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of Formulas (I), (II), (III), and (IV) is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons. First, these Formulas differ in structure and are not all members of a same recognized class, and further are not established in either the specification or the prior art as being functionally equivalent. Additionally, based on their disclosed/depicted structures, LRRK2 inhibitors of Formulas (I)-(IV) may not reasonably be considered as sharing a “single structural similarity”. It is noted that each of Formulas (I)-(IV) encompasses numerous alternative embodiments, which embodiments may reasonably be examined together based on their shared underlying structure; however, the Markush grouping of Formulas (I), (II), (III), and (IV) together is improper.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claim Interpretation
With respect to all claims, and particularly the limitation “subject…that has wild-type LRRK2 and a genetic modifier of wild type LRRK2 such that the subject will respond to the LRRK2 inhibitor” (independent claim 1), and the limitations “Parkinson’s disease associated with wild-type LRRK2” and “genetic modifier(s) of LRRK2” (independent claims 7 and 14), it is noted that the specification states that:
“recent evidence indicate indicates that some cases of PD are associated with increased activity of wild-type, i.e., non-mutant, LRRK2” (paragraph 3 of the published application);
“pathology in some patients with wild-type, i.e., non-mutant, LRRK2, appears to resemble that in patients with mutant LRRK2” and “LRRK2 activity is elevated in some PD patients with wild-type LRRK2” (paragraph 47);
a “genetic modifier of LRRK2 may be one or more genetic elements…that operably modifieds LRRK2 (e.g., wild-type LRRK2), e.g., that alters the expression, degradation, localization…binding, or activity of LRRK2” (paragraph 55);
“A genetic modifier may be in any region of the subject’s genome”, “may lie within a coding region or a non-coding region”, may lie within the LRRK2 coding region but not alter the sequence of the LRRK2 polypeptide, the size of the LRRK2 polypeptide, or both” (paragraph 55).
Based on the above description of “wild-type LRRK2” and “genetic modifier(s)” thereof, the recitation in the claims of “wild-type LRRK2” has been interpreted as referencing production of a wild-type LRRK2 protein, but encompassing genetic modifiers, including within the LRRK2 locus and gene (both coding and non-coding regions) that do not affect the sequence or size of the resulting LRRK2 protein in a manner that would result in that protein being considered mutant/non-“wild-type”.
With regard to the language “providing a LRRK2 inhibitor”/“providing the subject with a LRRK2 inhibitor” (see independent claims 1 and 14), it is noted that the specification states that an LRRK2 inhibitor “may be provided by any suitable route or mode of administration”, “may be provided according to a dosing regimen”, “may be provided at any suitable interval”, etc. (see paragraphs 200-206 of the published application, particularly paragraphs 200-202). As the term “providing” as used clearly does not require actual administration of a drug (given the nature of the way “providing” is employed), and as a limiting definition is not given, the term “providing” as employed in the claims encompasses any manner of such “providing”, including actual physical administration (via injection, implantable device, etc.), as well as activities such as providing to a patient a prescription or samples of a drug (but without a requirement for actual administering of the LRRK2 inhibitor).
With regard to the term “treating” (which appears in independent claims 1 and 14), it is noted that the specification states that “Because no cure for PD exists, current treatments focus on alleviating symptoms, particularly motor impairment” (published application at paragraph 4), and recites known “treatments” for management of PD (such as levodopa) (paragraph 54). Given the lack of a limiting definition of “treatment”/”treating”, and the discussion in the application of “treating” referring to symptom management, the term as employed in the claims is interpreted as encompassing a “treating” that results in managing PD symptoms.
Claim Objections
Claim 7 and claims dependent therefrom (claims 8-11 and 13) are objected to because of the following informalities: claim 7 recites. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)/second paragraph
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 2-4, 7-11, 13-14, 16-19, and 21 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.
Regarding claims 2-4, claim 2 recites the limitation "the genetic data". There is insufficient antecedent basis for this limitation in the claim (as the term “genetic data” is not previously employed). Further clarification is therefore needed with regard to how claims 2-4 further limit the claimed method.
Claim 7 and claims dependent therefrom (claims 8-11 and 13) are indefinite because it is unclear whether the claims do or do not require anything more than “conducting an assay” as set forth in the first step/activity of claim 7. The claim recites a method “of determining whether a subject having Parkinson’s disease associated with wild-type LRRK2 will respond to a LRRK2 inhibitor”, with the language “determining whether” suggesting that the claims may or may not achieve the recited result. However, the body of the claim recites “generating a report that identifiers one or more genetic modifiers” that are “indicative that the subject….will be responsive” and “providing the report to a physician…”; this later language, and particularly the recitation “report that identifies one or more genetic modifiers…..”, suggests that the method requires the actual result of achieving such an “identification” of one or more genetic modifiers. As there are multiple reasonable interpretations of the claim language that impart different boundaries on what is claimed, further clarification is needed.
Claims 7-11 and 13 are also indefinite over the recitation in independent claim 7 of the limitation “providing the report to a physician such that the physician prescribe or provide the subject with a LRRK2 inhibitor”. While it is clear that – to the extent that this activity is required (which is not clear, as noted above) – this limitation requires some manner/type of “providing the report” to a physician, the nature of/types of activities sufficient to meet the requirement of “providing” are not clear, and the further language “such that the physician prescribe or provide the subject with a LRRK2 inhibitor” is also confusing with regard to how it further limits what is required. This language could potentially be interpreted as a further requirement with respect to actual action of the referenced “physician”, or as an intended purpose of the “providing” (such that nothing more than providing the report in any manner/form is require), or potentially something in between these possible interpretations (e.g., a requirement that the physician receive and review a “report”), etc. As the meaning and boundaries of this claim language are not clear, further clarification is needed.
Regarding claims 9-10, claim 9 recites the limitation "the genetic modifier". There is insufficient antecedent basis for this limitation in the claim, as claim 7 recites “one or more genetic modifiers” but not any particular modifier that might constitute “the genetic modifier”. Due to this lack of clear antecedent basis, it is also unclear whether the further limitation applies to any/all “one or more genetic modifiers”, to a single modifier, etc. Further clarification is therefore required.
Regarding claim 14 and claims dependent therefrom (claims 16-19 and 21), claim 14 recites the limitation “the one or more genetic modifiers…” (see lines 3-4). There is insufficient antecedent basis for this limitation in the claim, as the claim previously refers to “one or more genetic modifier”. Further clarification is therefore needed with regard to what is being further limited.
Regarding claims 17-18, claim 17 recites the limitation "the genetic modifier". There is insufficient antecedent basis for this limitation in the claim, as claim 14 recites “one or more genetic modifier” and “one or more genetic modifiers” but not any particular modifier that might constitute “the genetic modifier”. Due to this lack of clear antecedent basis, it is also unclear whether the further limitation applies to any/all “one or more genetic modifier(s)”, to a single modifier, etc. Further clarification is therefore required.
Claim Rejections - 35 USC § 102
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 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.
Claim(s) 7-11 and 13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Nalls et al (Nature Genetics 46(9):989 [Sept 2014; online July 2014]; cited herein), including the cited supplementary material of Nalls et al (supplemental Figure separately cited herein), and with regard to the second embodiment discussed below, as evidenced by Kluss et al (Biochemical Society Transactions 47:651-661 [March 2019]; cited herein).
Nalls et al disclose a meta-analysis of Parkinson’s disease genome-wide association data (see entire reference), and report replicating their findings “in an independent sample series using a semi-custom genotyping array” (page 990, right column). Among the SNPs reported as having been both discovered and replicated is rs7690478 (see Table 1, noting that Nalls et al disclose detecting both an “effect allele” and an “alternative allele”, such that both positive and negative assay results are reported by Nalls et al); rs7690478 is disclosed in the application as a preferred SNP, and is recited in dependent claim 10. As Nalls et al report conducting a genotyping assay on samples from subjects with Parkinson’s disease with regard to a preferred SNP recited in the claims, including obtaining and reporting resulting “genetic data” that comprises “sequence data” (see again Table 1), Nalls et al anticipate claim 7, as well as dependent claims 8-10 (it is reiterated that methods in which only the “conducting” of claim 7 is performed are embraced by the present claim language, particularly in view of the recitation of “determining whether…” in the preamble of claim 7; see also the above indefiniteness rejection). With further regard to claim 11, Nalls et al further report performing genotyping with respect to “a series of proxy variants” for each most significant SNP (as depicted in Table 1), and thus also meet the requirement for “identifying a plurality of genetic modifiers”. With regard to claim 13, this claim is anticipated for the same reason claim 7 is anticipated, as the claims do not clearly require any actual actions/steps involving a LRRK2 inhibitor, particularly when the results of the “conducting an assay” are negative (rather, the references to LRRK2 inhibitors do not result in any manipulative difference between the claims and the cited prior art, and also add instructional steps to a known method, such that they constitute non-functional descriptive material (see MPEP 2111.05).
With regard to the alternative embodiment of the claims that appears to require an association between a “genetic modifier” indicative of responsiveness to an LRRK2 inhibitor in the presence of “wild-type LRRK2”, it is also noted that:
a) Nalls et al describe “LRRK2” as the “nearest gene” to rs76904798 (see, e.g., Table 1), and the cited Supplemental Material of Nalls et al depicts rs76904798 as being located upstream of the coding region of LRRK2; thus, the teachings of Nalls et al reference this SNP as a type of “genetic modifier” that is “associated with wild-type LRRK2”)(as opposed to being associated with a coding change/mutated form of LRRK2); and
b) Kluss et al refer to Nalls et al’s reported findings regarding rs76904798 as suggesting that the T allele associates with increased LRRK2 expression (while also confirming that this variant is considered a “non-coding” variant, meeting the requirement of being a “wild-type” variant as disclosed in the application)(see page 653 under the heading “GWAS suggest modified expression of LRRK2 is associated with sporadic PD”), such that these teachings of Kluss et al provide further evidence that the variant taught by Nalls et al meets the requirements of the claims.
Thus, the disclosure of Nalls et al, which includes provision of a report of their data in the form of publication of the data of their Table 1 (which constitutes a type of “providing a report”, also as evidenced by Kluss et al’s reference to their published findings), also meets the requirements of the claims with regard to this second embodiment.
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 1-4, 6-11, 13-14, 16-19, and 21 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
While it is reiterated that claims 7-11 and 13 are anticipated for the reasons given above, in the interest of compact prosecution this rejection has also been applied to those claims to the extent that they require the prescribing or providing of an LRRK2 inhibitor to a subject based on a finding of genetic modifier(s) as specified in the claims that are ‘indicative that the subject….will be responsive to a LRRK2 inhibitor”.
There are many factors to be considered when determining compliance with the enablement requirement of 35 USC 112(a), including, but 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. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). All evidence related to each of these factors has been considered, and the conclusion that enablement is lacking, as set forth below, is based on the evidence as a whole. (MPEP 2164.01(a)).
Claim 1 and claims dependent therefrom (claims 1-4 and 6) are drawn to methods “of treating a subject having Parkinson’s disease associated with wild-type LRRK2”, comprising ‘providing a LRRK2 inhibitor to a subject that presents with Parkinson’s disease and that has wild-type LRRK2 and a genetic modifier of wild type LRRK2 such that the subject will respond to the LRRK2 inhibitor, thereby treating Parkinson’s disease associated with wild-type LRRK2 in the subject”; these claims thus require successfully “treating” as subject as specified. Claim 14 and claims dependent therefrom (claims 16-19 and 21) are also directed to a method “of treating a subject having Parkinson’s disease associated with wild-type LRRK2”, the method comprising “receiving genetic data that identifies one or more genetic modifier of LRRK2, wherein the one or more genetic modifiers are indicative that the subject having Parkinson’s disease associated with wild-type LRRK2 will be responsive to a LRRK2 inhibitor” and “prescribing or providing the subject with a LRRK2 inhibitor” (such that the claims encompass a method of “treating” that requires “prescribing or providing” a LRRK2 inhibitor, which also encompasses performing such steps based on the referenced “genetic data”. Claim 7 and claims dependent therefrom (claims 8-11 and 13) – as noted above – also appear to potentially be directed to methods that require the prescribing or providing of an LRRK2 inhibitor to a subject based on a finding of genetic modifier(s) as specified in the claims that are ‘indicative that the subject….will be responsive to a LRRK2 inhibitor”.
It is unpredictable as to whether one of skill in the relevant art could actually perform/use the claimed invention. The specification provides many examples of possible LRRK2 inhibitors (including the elected species of inhibitor), but the actual data provided in the specification is limited to the provision of sequencing data analyzed for “potential modifiers” of LRRK2 inhibitor response (see Example 1). Applicant has provided no evidence of any treatment of any type of Parkinson’s disease (PD) patient with an LRRK2 inhibitor, which includes treatment of any kind, as well as treatment that is targeted to PD patients having “genetic modifiers” and wild-type LRRK2 as recited in the claims. Lacking enabling guidance in the specification, one of skill in the art may look to the teachings of the prior art for further guidance sufficient to enable what is claimed. However, in this case, the prior art as exemplified by Kluss et al (Biochemical Society Transactions 47:651-661 [March 2019]; cited herein), while discussing the “translational potential of LRRK2-specific kinase inhibitors for the treatment of PD”, teaches that “it remains unclear as to which patients would benefit from such a therapy”, that “the downstream effects of inhibiting this enzymatic activity in humans are currently unknown”, and that “human safety data will be critical to whether LRRK2 kinase inhibitors can be tolerated clinically in PD patients” (see entire reference, particularly the Abstract and pages 656-657). Further, Atashrazm et al (Clinical Pharmacology: Advances and Applications 8:177 [2016]; cited herein), while providing an overview of KRRK2 inhibitors in development for potential use as PD treatments, teach that developing such inhibitors for actual use (and even safe clinical trials) in humans has been challenging, stating that further “research to understand LRRK2 function and build evidence of LRRK2 inhibitor efficacy will aid in the translation of these drugs to potential clinical trials”, i.e., such inhibitors are not yet established as being functional in actually treating PD (or even as being safe to use in PD patients) (see entire reference, particularly the discussion of “Preclinical efficacy testing” on pages 181-182, “Preclinical safety testing” on pages 182-184, and “Challenges for advancing to clinical trials” on pages 184-186, as well as page 187, top of left column). With more particular regard to the elected species of inhibitor, while Koestler et al (WO2021/048618A1 [18 March 2021, filed 11 Sept 2020, with priority to 13 Sept 2019]; cited herein) disclose such a purported LRRK2 inhibitor and assert that it may be used in treatment of a wide variety of conditions including PD (see entire reference, particularly the Abstract, pages 1-2 and 10), evidence supporting the actual successful use of the inhibitor in treating PD is not provided. Thus, it is clear from these teachings of the relevant art that methods of “treating” requiring the activities specified in the claims, including with regard to the elected species of LRRK2 inhibitor, were not known to function in PD treatment as of Applicant’s effective filing date (with the art rather suggesting unpredictability and a lack of enablement of the claimed invention). Given the high skill level of one skilled in the relevant art, it is within the ability of such an artisan to, e.g., perform further experimentation aimed at identifying LRRK2 inhibitors that may potentially be employed successfully as recited in the claims. However, the safe and effective use of such inhibitors has not been established, and it is unknown and unpredictable as to what the outcome of such further research may be, and whether any amount of experimentation will ultimately be sufficient to enable what is claimed. Accordingly, based on the totality of the evidence (and particularly given the lack of enabling guidance in both the specification and the prior art), it would require undue experimentation to practice/use the claimed invention. With further regard to dependent claims 2-4, 8-11, and 16-19, these claims are further limiting of “genetic modifiers” of “wild-type LRRK2”; as discussed above, enablement is lacking with regard to all embodiments requiring “treating” PD with an LRRK2 inhibitor (regardless of whether such a modifier is present or not; neither the specification nor the prior art provide guidance that enables use of such inhibitors in treating the recited type of patient/subject). Regarding dependent claims 6, 13, and 21, the elected species of inhibitor is addressed above.
Claims 1-4, 6-11, 13-14 16-19, and 21 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. This is a written description rejection.
It is again noted that claims 7-11 and 13 are anticipated for the reasons given above; however, this rejection applies to those claims to the extent that they require “treating” a subject by prescribing or providing of an LRRK2 inhibitor to a subject based on a finding of genetic modifier(s) as specified in the claims that are ‘indicative that the subject….will be responsive to a LRRK2 inhibitor”.
With regard to a complying written description of an invention, MPEP 2163.02 states:
Whenever the issue arises, the fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, inventor was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991). An applicant shows that the inventor was in possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. Am. Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the inventor was in possession of the claimed invention. See, e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998); Regents of the Univ. of Cal. v. Eli Lilly, 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997); Amgen, Inc. v. Chugai Pharm., 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by “whatever characteristics sufficiently distinguish it”).
The limitations at issue in the present claims are the requirements to “treat” a subject having PD including by providing and/or prescribing an LRRK2 inhibitor (including the elected species thereof) (which is encompassed by all of the independent claims as discussed above in the enablement rejection), as well as the requirement to provide successful treatment to a subset of patients having a “genetic modifier” of wild-type LRRK2 (which again is embraced by all of the claims, with some reciting specific SNPs, and others any “genetic modifier”). While the specification discloses genetic modifiers that may purportedly be employed in the manner set forth in the claims, as well as a variety of potential LRRK2 inhibitors, the actual “treating” required by the claims has not been reduced to practice; rather, the actual data provided in the specification is limited to the provision of sequencing data analyzed for “potential modifiers” of LRRK2 inhibitor response (see Example 1). While guidance of the type provided in the specification is sufficient to describe and establish possession of those embodiments of independent claim 7 and claims dependent therefrom that pertain to simply “conducting an assay” – and while it might be sufficient to establish possession were the disclosures of the specification related to, e.g., drugs known in the art to actually function in treating PD patients, including with regard to patients having “genetic modifiers” of the type of the claims - the state of the prior art is such that it cannot be relied upon in supporting an adequate description of the present invention. Rather, as was discussed above:
a) the prior art as exemplified by Kluss et al, while discussing the “translational potential of LRRK2-specific kinase inhibitors for the treatment of PD”, teaches that “it remains unclear as to which patients would benefit from such a therapy”, that “the downstream effects of inhibiting this enzymatic activity in humans are currently unknown”, and that “human safety data will be critical to whether LRRK2 kinase inhibitors can be tolerated clinically in PD patients” (see entire reference, particularly the Abstract and pages 656-657);
b) Atashrazm et al, while providing an overview of KRRK2 inhibitors in development for potential use as PD treatments, teach that developing such inhibitors for actual use (and even safe clinical trials) in humans has been challenging, stating that further “research to understand LRRK2 function and build evidence of LRRK2 inhibitor efficacy will aid in the translation of these drugs to potential clinical trials”, i.e., such inhibitors are not yet established as being functional in actually treating PD (or even as being safe to use in PD patients) (see entire reference, particularly the discussion of “Preclinical efficacy testing” on pages 181-182, “Preclinical safety testing” on pages 182-184, and “Challenges for advancing to clinical trials” on pages 184-186, as well as page 187, top of left column); and
c) with more particular regard to the elected species of LRRK2 inhibitor, while Koestler et al (WO2021/048618A1 [18 March 2021, filed 11 Sept 2020, with priority to 13 Sept 2019]; cited herein) disclose such a purported LRRK2 inhibitor and assert that it may be used in treatment of a wide variety of conditions including PD (see entire reference, particularly the Abstract, pages 1-2 and 10), evidence supporting the actual successful use of the inhibitor in treating PD is not provided.
Thus, it is clear from these teachings of the relevant art that methods of “treating” requiring the activities specified in the claims, including with regard to the elected species of LRRK2 inhibitor, were not known to function in PD treatment as of Applicant’s effective filing date. Further, this also applies to the subgenus of “treatments” applied with regard to subjects having more particular specific genetic modifiers, including those disclosed in the specification (as successful treatment has not been shown with regard to any subject, including such particular types of subjects). Accordingly, a sufficient written description to establish possession of the claimed invention is lacking.
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 1-4, 6-11, 13-14, 16-19, and 21 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exceptions (JEs) without significantly more.
Independent claim 1 (from which claims 3-4 and 6 depend) recites a subject “having Parkinson’s associated with wild-type LRRK2” and more specifically “has wild-type LRRK2 and a genetic modifier of wild type LRRK2 such that the subject will respond to the LRRK2 inhibitor”; these underlying biological/genetic characteristics of a patient with PD are a natural phenomenon/law of nature. Such natural phenomenon are also recited in independent claim 7 (from which claims 8-11 and 13 depend) (with claim 7 reciting PD “associated with wild-type LRRK2” and “genetic modifiers…. indicative that the subject having Parkinson’s disease associated with wild type LRRK2 will be responsive…” and independent claim 14 (from which claims 16-19 and 21 depend)(with claim 14 reciting PD “associated with wild-type LRRK2” and “genetic modifiers…indicative that a subject having Parkinson’s disease associated with wild type LRRK2”). Independent claim 7 additionally recites “determining whether a subject…..will respond to a LRRK2 inhibitor”, which is a conclusion based on test/assay results that may be formed entirely in the human mind, i.e., an abstract idea (another type of JE).
This judicial exceptions are not integrated into a practical application because none of the claims require any steps/actions amounting to more than data gathering, i.e., insignificant extrasolution activity. With regard to the activities of “providing”/ ”prescribing” inhibitors, it is reiterated that claim language as interpreted herein does not require actual administration of an inhibitor to a patient (such that the claims cannot be considered as requiring a “particular treatment” that amounts to a practical application). Independent claim 1 does not recite any other actions beyond a “providing” in such a manner that the recited inhibitor might or might not be used by the PD patient. Independent claim 7 encompasses (based on at least one reasonable interpretation) merely “conducting an assay” that might or might not result in any further action being taken, and which clearly constitutes nothing more than gathering data/information. Claim 14 recites the noted type of “prescribing or providing” in combination with “receiving genetic data”, which is again a type of data gathering that constitutes insignificant extra-solution activity.
The claim(s) also do not include additional elements that are sufficient to amount to significantly more than the judicial exception. Independent claim 1 requires nothing more that the recited “providing” that could potentially be considered as amounting to “significantly more”. Independent claim 7 broadly recites “conducting an assay on a sample…in order to obtain genetic data”, which clearly constitutes well-understood, routine, and conventional activity (as evidenced by, e.g., the teachings of Nalls et al discussed above). Independent claim 14 recites a combination of “receiving genetic data” and “prescribing or providing” that may be performed in any order relative to one another; as already noted such a “prescribing or providing” need not result in any action being taken/performed with regard to the recited subject, and “receiving data” encompasses receiving information (as opposed to any type of active/manipulative step that could potentially add something “significantly more”). It is also noted that generally recited activities such as “conducting an assay” to “obtain genetic data” correspond to types of laboratory techniques/activities that the courts have recognized as well-understood, routine, and conventional activity in the life science arts when claimed a generic manner (as they are in the instant claims); see MPEP 2106.05(d)(II). Further, to the extent that the claim may embrace embodiments requiring actual administration of LRRK2 inhibitors, MPEP 2106.03(II) states that: “A claim whose BRI covers both statutory and non-statutory embodiments embraces subject matter that is not eligible for patent protection and therefore is directed to non-statutory subject matter”
Regarding dependent claims 2-4, 8-11, and 16-19, these claims simply recite more particular types of genetic information that may be gathered (i.e., more specific types of natural phenomena); nothing amount to “significantly more” than a JE, or an application of a JE, is required. Regarding dependent claims 6, 13, and 21, while these claims reference more specific types of LRRK2 inhibitors, the actual administration of such inhibitors (i.e., a possible “particular treatment”) is not required by the present claim language (such that the analysis that applies to claims 1, 7, and 14 also applies to these dependent claim).
Accordingly, none of claims 1-4, 6-11, 13-14, 16-19, and 21 is directed to patent eligible subject matter.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-4, 6-11, 13-14, 16-19, and 21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of copending Application No. 19/480,142 (currently unpublished). Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
The instant claims and the ’142 claims each encompass methods of treating with (including by providing/prescribing) a LRRK2 inhibitor a subject with PD “associated with wild-type LRRK2” and a “genetic modifier of wild type LRRK2 such that the subject will respond” to the LRRK2 inhibitor. ’142 independent claim 1 recites such a “treating” by “providing” (analogous to instant independent claim 1), and also reciting groups of alternative SNPs that correspond to the “genetic modifier”; ‘142 independent claim 2 recites a “conducting an assay” followed by generating and providing a report (analogous to instant independent claim 7, while also including recited preferred SNPs); and ‘142 independent claim 3 recites “receiving genetic data” regarding genetic modifiers and “prescribing or providing” an LRRK2 inhibitor (analogous to instant independent claim 14 and again including recited preferred SNPS); the ’142 dependent claims further include embodiments of inhibitor corresponding to those of the instant claims, including the elected species (see, e.g., ‘142 dependent claim 5). With regard to instant claims 1-3, 6, 7-9, 11, 13, 14-17, 19, and 21, the ‘142 claims recites species that are encompassed by the instant claims, and thus anticipate those claims. With regard to instant dependent claims 4, 10, and 18, while it is noted that the ‘142 claims do not recited the elected SNP, they do recite the alternative SNP examined herein – rs76904798 – and thus also suggest the invention under consideration herein, rendering it obvious. As such, instant claims 1-4, 6-11, 13-14, 16-19, and 21 are not patentably distinct from the ’142 claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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/DIANA B JOHANNSEN/Primary Examiner, Art Unit 1682
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