DETAILED CORRESPONDENCE
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 .
This action is in response to the papers filed April 20, 2026. Currently, claims 10-16, 19-24, 26-27, 31-33 are pending. Claims 26-27, 31-33 have been withdrawn as drawn to non-elected subject matter.
Election/Restrictions
Applicant's election with traverse of Group I, Claims 10-19, 19-24 in the paper filed April 20, 2026 is acknowledged.
The response argues no serious burden has been show and cites MPEP 803. This argument has been reviewed but is not persuasive. The instant application is a 371 application. The standard for restriction in 371 applications is Lack of Unity. The lack of unity standard does not include burden. Thus, the examiner does not have to articulate a rationale for burden. The examiner separated the inventions based on lack of unity and there was no contribution over the art. Thus, restriction is proper.
Claims 26-27, 31-33 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
The requirement is still deemed proper and is therefore made FINAL.
This application contains claims 26-27, 31-33 are drawn to an invention nonelected with traverse in the paper filed April 20, 2026. A complete reply to the final rejection must include cancellation of nonelected claims or other appropriate action (37 CFR 1.144) See MPEP § 821.01.
Priority
This application is a 371 of PCT/US22/25469, filed April 20, 2022 and claims priority to provisional 63/177,189, filed April 20, 2021.
Drawings
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - Sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.831(c). Sequence identifiers for sequences (i.e., “SEQ ID NO:X” or the like) must appear either in the drawings or in the Brief Description of the Drawings. Figure 1 and 4 have sequences that are not identified by SEQ ID NO:. Correction is required.
Required response – Applicant must provide:
Amended drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers (i.e., “SEQ ID NO:X” or the like) into the Brief Description of the Drawings, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Claim Objections
Claims 14, 17, 18 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim. Claim 14 depends on 12 or 13. 12 is a multiple dependent claim. A multiple dependent claim may not serve as a basis for any other multiple dependent claim, either directly or indirectly. These limitations help to avoid undue confusion in determining how many prior claims are actually referred to in a multiple dependent claim. See MPEP § 608.01(n). Claims 17 and 18 also depend on multiple dependent claims. Accordingly, the claims 14, 17-18 not been further treated on the merits.
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 10-13, 15-16 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
35 U.S.C. § 101 requires that to be patent-eligible, an invention (1) must be directed to one of the four statutory categories, and (2) must not be wholly directed to subject matter encompassing a judicially recognized exception. M.P.E.P. § 2106. Regarding judicial exceptions, “[p]henomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.” Gottschalk v. Benson, 409 U.S. 63, 67 (1972); see also M.P.E.P. § 2106, part II.
Based upon consideration of the claims as a whole, as well as consideration of elements/steps recited in addition to the judicial exception, the present claims fail to meet the elements required for patent eligibility.
Question 1
The claimed invention is directed to a process that involves a natural principle and a judicial exception.
Question 2A Prong I
The claims are taken to be directed to an abstract idea, a law of nature and a natural phenomenon.
Claim 10 is directed to “a method of treating a subject with a therapeutic agent that treats or inhibits malignant mesothelioma”.
Claim 10 is directed to a process that involves the judicial exceptions of an abstract idea (i.e. the abstract steps of “determining if the subject has a genotype” and “wherein the presence of a genotype having the LRRK2 variant indicates the subject has an increased risk of developing malignant mesothelioma”) and a law of nature/natural phenomenon (i.e. the natural correlation between the LRRK1 variant and malignant mesothelioma).
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons that follow.
Herein, claim 10 involves the patent-ineligible concept of an abstract process. Claim 10 requires performing the step of “determining if the subject has a genotype”. Neither the specification nor the claims set forth a limiting definition for "determining" and the claims do not set forth how “determining” is accomplished. As broadly recited the determining step may be accomplished mentally by thinking about a subject’s genotype. Thus, the determining step constitutes an abstract process idea.
A correlation that preexists in the human is an unpatentable phenomenon. The association between LRRK2 genotype and increased risk of developing malignant mesothelioma is a law of nature/natural phenomenon. The wherein clause which tells users of the process to predict malignant mesothelioma in the sample, amounts to no more than an "instruction to apply the natural law". This wherein clause is no more than a mental step. Even if the step requires something more such as to verbalize the discovery of the natural law, this mere verbalization is not an application of the law of nature to a new and useful end. The wherein clause does not require the process user to do anything in light of the correlation. The wherein clause fails to provide the “practical assurance” sought by the Prometheus Court that the “process is more than a drafting effort designed to monopolize the law of nature itself.”
Question 2A Prong II
The exception is not integrated into a practical application of the exception. The claims do not recite any additional elements that integrate the exception into a practical application of the exception. While the claim recites obtaining a sample and performing an assay to genotype LRRK2 variant nucleic acid, this is not an integration of the exception into a practical application. Instead, these elements are data gathering required to perform the method. Thus, the claim is “directed to” the exception.
Further, the claim recites if the subject doesn’t have a genotype comprising LRRK2 variant, the subject is administered a standard dosage of a therapeutic agent and if the subject has a genotype comprising LRRK2 variant the same as or greater than a standard dosage amount is administered. The claim encompasses administering the standard dosage to subjects with and without the LRRK2 variant. The same treatment is administered regardless of variant status, thus, this is not an integration of the judicial exception.
Even more, the generic treatment of a “therapeutic agent that treats or inhibits malignant mesothelioma” is not a particular treatment. The instant claims are directed to administering the standard dosage of an unspecified therapeutic agent to both patients with the variant and without the variant. This is not a step of treating the patient with a particular medication tailored to the patient’s genotype. As such, this claim is directed to the relationship and is not a practical application of the judicial exception.
Question 2B
The second step of Alice involves determining whether the remaining elements, either in isolation or combination with the other non patent ineligible elements, are sufficient to “’transform the nature of the claim’ into a patent eligible application” Alice, 134 S. Ct. at 2355 (quoting Mayo, 132 S. Ct. at 1297).
The claims are not sufficiently defined to provide a method which is significantly more from a statement of a natural principle for at least these reasons:
The claims do not include applying the judicial exception, or by use of, a particular machine. The claims do not tie the steps to a “particular machine" and therefore do not meet the machine or transformation test on these grounds. The use of machines generally does not impose a meaningful limit on claim scope.
The claims also do not add a specific limitation other than what is well-understood, routine and conventional in the field. The determining whether the subject has LRRK2 variants is a mere data gathering step that amounts to extra solution activity to the judicial exception. It merely tells the users of the method to determine the variant of a sample without further specification as to how the sample should be analyzed. The claim does not recite a new, innovative method for such determination. The determining step essentially tells users to determine the markers through whatever known processes they wish to use.
The step of determining variants in LRRK2 was well known in the art at the time the invention was made. The prior art teaches that LRRK2 variants were routinely determined by sequencing. The steps are recited at a high level of generality. The claim merely instructs a scientist to use any variant analysis to determine the mutation status. The claims do not require the use of any particular non-conventional reagents. When recited at this high level of generality, there is no meaningful limitation that distinguishes this step from well understood, routine and conventional activities engaged in by scientists prior to applicant’s invention and at the time the application was filed.
Additionally, the teachings in the specification demonstrate the well understood, routine, conventional nature of additional elements because it teaches that the additional elements were well known. Specifically, the specification teaches the nucleotide sequence of LRRK2 reference nucleic acid is GRCh38/hg38, ENST0000298910.12 which was known and sequenced in the prior art (page 23, lines 16). The art teaches a large number of mutations in LRRK2 are associated with Parkinson’s disease. As such, methods of detecting LRRK2 variants were well known in the art.
Further it is noted that the courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity.
Analyzing DNA to provide sequence information or detect allelic variants, Genetic Techs., 818 F.3d at 1377; 118 USPQ2d at 1546;
Amplifying and sequencing nucleic acid sequences, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014)
For these reasons the claims are rejected under section 101 as being directed to non-statutory subject matter.
Claim Rejections - 35 USC § 112-Description
The following is a quotation 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.
Claim 10 is 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are broadly drawn to methods which comprise identifying any structurally undefined variant in the gene encoding LRRK2 which possess the functionality of being associated with increased risk of developing malignant mesothelioma.
Relevant to the lack of particular structural limitations in the rejected claims drawn to nucleic acids, MPEP 2163 states:
The claimed invention as a whole may not be adequately described if the claims require an essential or critical feature which is not adequately described in the specification and which is not conventional in the art or known to one of ordinary skill in the art.
Ariad Pharmaceuticals Inc. v. Eli Lilly & Co., 94 USPQ 2d 1161 (Fed. Cir. 2010) recently re-affirmed the written description requirement. Ariad reiterates that “the hallmark of written description is disclosure" and “possession as shown in the disclosure” is a more complete formulation of the test for written description. Ariad considers situations of genus claims and states that the written description requirement ensure that "when a patent claims a genus by its function or result, the specification recites sufficient materials to accomplish that function."
In the case of the instant claims, the functionality of identifying variants diagnostic of increased risk of developing malignant mesothelioma is a critical feature of the claimed methods.
The specification teaches a single deletion mutation of AAAGGTAAGG (SEQ ID NO: 3). The specification further states that is “is believed that no variants of the LRRK2 gene or protein have any known association with a malignant mesothelioma (page 7, lines 29-32).
The art teaches there are nearly 4100 variants in LRRK2 gene (see ClinVar, National Library of Medicine).
PNG
media_image1.png
784
1528
media_image1.png
Greyscale
Neither the art nor the specification provide any guidance which of these 4068 variants are indicative the subject has an increased risk of developing malignant mesothelioma. Given the guidance in the specification and what was taught in the art prior to the invention, the skilled artisan would be unable to predictably correlate structural changes in the gene encoding LRRK2 with malignant mesothelioma, simply based on their existence.
In analyzing whether the written description requirement is met for a genus claim, it is first determined whether a representative number of species have been described by their complete structure. With respect to claims which encompass variants, no common structural attributes identify the members of the genus. The current claims encompass a large genus of nucleic acids which comprise variants in any region of any LRRK2 nucleic acid. The genus includes an enormous number of variants, polymorphisms and mutations for which no written description is provided in the specification. This large genus is represented in the specification by only the particularly named single deletion mutation of AAAGGTAAGG (SEQ ID NO: 3) for which data is provided. The genus of variants encompasses SNPs, deletions, insertions, translocations, microsatellites, for example. The claims encompass a genus of structurally undefined polymorphisms which require a specific functionality. The genus includes a large number of polymorphisms and mutations for which no written description is provided in the specification. The disclosure in the specification does not provide for a predictable association with any variant in the LRRK2 gene as is broadly claimed. Here, no common element or attributes of the sequences are disclosed which would permit selection of sequences as polymorphisms. No structural limitations or requirements which provide guidance on the identification of sequences which meet the functional limitations of being indicative of malignant mesothelioma provided. The specification provides no correlation between the structure of the recited polymorphisms and the claimed function of such polymorphisms. Therefore, the polymorphisms are not representative of the genus of any polymorphism associated with malignant meothelioma because it is not clear which polymorphisms or mutations within the coding or non-coding region of the TREX1 gene would have the same affect. Therefore, the specification fails to teach how to distinguish members of the claimed genus of polymorphisms and variants which possess the claimed functionality from non members.
Thus considering the breadth of the polynucleotides required by the claimed methods, their specific required functionalities, and the teachings of the instant specification, it is the conclusion that the specification does not provide an adequate written description of the broadly claimed subject matter.
Claim Rejections - 35 USC § 112- 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.
Claims 10-13, 15-16, 19-24 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 pre-AIA the applicant regards as the invention.
Claim 10 recites a “standard dosage amount” of the therapeutic agent that treats or inhibits malignant mesothelioma. The recitation “standard dosage amount” is indefinite because it is unclear what the standard dosage amount is. The specification does not provide any standard or guidance of how to determine the standard dosage amount or what the standard is relative to. Thus, specification provides no metes and bounds for the term and it is unclear the boundaries to determine what dosage is "standard". Clarification is required.
Claim 11 recites a deletion of the nucleotides….(SEQ ID NO: 3) located at positions corresponding to positions….according to SEQ ID NO:1. It is unclear what “corresponding” is intended to encompass. It is unclear if this means the position is not the recited positions of SEQ ID NO: 1. Claim 12-13, 15-16 use similar language. Applicant may wish to amend the claims to require a deletion of nucleotides AAAGGTAAGG (SEQ ID NO: 3) located at positions 97,182 to 97,191 of SEQ ID NO: 1.
Claims 13, 20-21 are directed to a primer that is proximate to positions 97,182-97,181 of SEQ ID NO: 1. The language proximate is a relative term. It is unclear what makes something proximate and something that is not proximate. The metes and bounds of the claimed invention are unclear. Correction is required.
Claim 21 is directed to sequencing “the entire nucleic acid molecule”. “The entire nucleic acid molecule” lacks proper antecedent basis. It is unclear what the nucleic acid molecule is referring to. It is unclear whether the molecule is the deletion, the gene, LRRK2, the chromosome or some other nucleic acid molecule. Correction is required.
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.
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 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(s) 19-21 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Paisan-Ruiz et al (Human Mutation, Vol. 29, No. 4, pages 485-490, 2008).
Paisan-Ruiz teaches a comprehensive analysis of LRRK2 by sequencing the large gene for mutations. Paisan-Ruiz teaches screening the entire coding sequence (abstract). Paisan-Ruiz teaches PCR analysis was performed using forward and reverse primers designed by Exon Primer (page 486, col. 2). Thus, Paisan-Ruiz teaches determining “whether” a nucleic acid molecule comprises a deletion mutation. Paisan-Ruiz did not identify the deletion mutation which is encompassed by determining whether or not the nucleic acid comprised the nucleic acid sequence comprising the SEQ ID NO: 3 deletion.
With respect to Claim 20, the primers were configured for each exon so a primer hybridized “proximate” the deletion mutation of SEQ ID NO: 3.
With respect to Claim 21, the assay sequenced the entire coding region, namely the entire nucleic acid molecule.
Conclusion
No claims allowable.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Cheung et al. (Human Molecular Genetics, Vol. 30, No. 18, pages 1750-1761, May 18, 2021) teaches LRRK2 mutations associated with mesothelioma. This is applicant’s post-filing art describing the mutation in 12 MM patients.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEANINE ANNE GOLDBERG whose telephone number is (571)272-0743. The examiner can normally be reached Monday-Friday 6am-3:30pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Winston Shen can be reached on (571)272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JEANINE A GOLDBERG/Primary Examiner, Art Unit 1682
May 5, 2026
Prosecution Insights