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 .
Status
The Art Unit location of your application at the USPTO has changed. To aid in correlating any papers for this application, all further correspondence regarding this application should be directed to Examiner Christina Borgeest, Art Unit 1675.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-12 and 20) in the reply filed on 06/28/2026 is acknowledged. Upon further consideration, claims 13-19 are hereby rejoined and the restriction requirement between inventions I and II, as set forth in the Office action mailed on 04/23/2026, is hereby withdrawn. In view of the withdrawal of the restriction requirement, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Claims 1-20 are under examination.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) and 365(c) is acknowledged. Based on an inspection of the prior applications, the examiner has concluded that the subject matter defined in instant claims 1-20 is supported by the disclosure in provisional application serial no. 63/195,903 and PCT/QA2022/050010. Therefore, the priority date of claims 1-20 of the instant application is deemed to be 06/02/2021.
Claim Objections
Claims 2 and 3 are objected to because of the following informalities. The terms “αSynuclein” and “real-time quaking-induced conversion” should be written out the first time they appear in the claims, followed by the acronyms αSyn and RT-QuIC, respectively, in parentheses. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 9-19 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. Claims 9 and 13 recite administration of at least one of “αSyn targeting agents, NPT200-11, ambroxol”, among others. According to the instant specification, paragraph [0060], the αSyn targeting agents are described thus: “αSyn targeting agents including NPT200-11 and ambroxol” (emphasis added by examiner). The word “including” in the specification presents NPT200-11 and ambroxol as examples or species of the class of αSyn targeting agents. Description of examples and preferences is properly set forth in the specification rather than in a single claim. See MPEP § 2173.05(d).
Claims 10-12 and 14-19 are hereby included in this rejection for depending upon an indefinite claim without resolving the indefiniteness.
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 1-8 and 20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more. The claims recite methods of diagnosing a synucleinopathy comprising homogenizing a tissue sample from a patient, centrifuging the homogenized tissue to form a supernatant and a pellet, wherein said supernatant comprises an aqueous-soluble fraction, resuspending the pellet in a detergent, then centrifuging the resuspended pellet to form a supernatant comprising a detergent-soluble fraction; quantifying the seeding activity of the aqueous-soluble fraction; comparing the differences in seeding activity of the aqueous-soluble and detergent soluble fractions, wherein said differences are indicative of Parkinson’s disease (PD) or dementia with Lewy bodies (DLB). Claim 20 recites a method for diagnosing a synucleinopathy comprising comparing the differences in seeding activity of the aqueous-soluble and detergent soluble fractions of a homogenized tissue sample, wherein said differences are indicative of PD or DLB. Thus, the claims are drawn to processes (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 diagnosing a synucleinopathy (PD or DLB) comprising quantifying and comparing αSyn seeding activity of aqueous-soluble and detergent soluble fractions, wherein differences are indicative of disease. The judicial exception is the relationship between αSyn seeding activity, i.e., whether the activity is higher in a given tissue and/or fraction (see claims 4, 5, 15, 16) and the presence of a synucleinopathy. The mental step of comparing biomarker levels, in this case, αSyn seeding activity, 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 the active steps of homogenizing, centrifuging, resuspending and quantifying seeding activity, although “quantifying” also encompasses a mental step. Claim 20 does not actually require any active steps but rather requires only comparing differences in seeding activity in a homogenized sample. In the case of claim 1 and its dependents, the steps of homogenizing, centrifuging and resuspending in a sample encompass sample collection and preparation, which are the necessary data gathering techniques required in order to perform the mental analysis steps. The discovery of the relationship between differences in αSyn seeding activity and the presence of synucleinopathies 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. Claims 3 and 14 recite performing an RT-QuIC assay using purified αSyn. The prior art discloses RT-QuIC assays; for instance, see Green (WO2018/007817), which teaches quantifying full-length αSyn (1-140), as well as shorter fragments using RT-QuIC (see p. 7, lines 6-9; pages 17-19). Green also teaches the reaction sample comprises an aqueous solution (p. 5, lines 28-29). Groveman et al. (Acta Neuropathologica Communications (2018) 6:7 doi 10.1186/s40478-018-0508-2) teach quantifying αSyn via RT-QuIC in samples comprising detergent (see pages 4-5 under αSyn RT-QuIC protocol and p. 5, left column, last paragraph). In addition, Poggiolini et al. (Biomolecules 2021, 11,820. https://doi.org/10.3390/biom11060820—on IDS filed 12/01/2023) disclose measuring αSyn (αSyn (1-140), αSyn (1-115) and αSyn (1-130)) in samples comprising TBS which “represents the aqueous soluble fraction” followed by resuspension of the pellet in detergent, which represents the detergent-soluble fraction (see p. 3, last paragraph; p. 5, Figure 1b; p. 6, Figure 2). For a claim reciting a judicial exception 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 additional steps are simply 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)). Thus, the claims are not patent eligible.
Note, claims 9-12 are not included in this rejection because claim 9 affirmatively requires treating a diagnosed synucleinopathy comprising administering one of the recited particular treatments.
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 9-19 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.
In deciding whether the application complies with the written description requirement of 35 USC 112(a) or 35 USC 112 (pre-AIA ), first paragraph, it is necessary to understand what Applicant is claiming and what Applicant has possession of. Claims 9 and 13 recite administering “αSyn targeting agents” to treat a synucleinopathy, namely Parkinson’s Disease (PD) or dementia with Lewy bodies (DLB). The αSyn targeting agent encompasses any molecule having any structure (e.g., polypeptide, antibody, nucleic acid or small molecule) capable of contacting αSyn. Therefore, the claims encompass a genus of αSyn modulating agents. The MPEP 2163(A) states “‘[a]n invention described solely in terms of a method of making and/or its function may lack written descriptive support where there is no described or art-recognized correlation between the disclosed function and the structure(s) responsible for the function.’” For inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession. (See MPEP 2163(II)(A)(3)(a)(i)).
To provide evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. According to the specification, Applicant has possession of the αSyn targeting agents, NPT200-11 and ambroxol. Price et al. (Sci Rep 8, 16165 (2018). doi.org/10.1038/s41598-018-34490-9) teach that NPT200-11 is a small molecule inhibitor of αSyn misfolding. Lin et al. (Int. J. Mol. Sci. 2024, 25, 12114. doi.org/10.3390/ ijms252212114) teach that the mucolytic drug, ambroxol, commonly used to treat coughs, may have potential in clearing αSyn aggregates (see abstract, p. 7, Figure 3 legend; paragraph bridging pages 9-10). Thus, the specification describes two possible species within a large genus of possible αSyn targeting agents. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). Except for NPT200-11 and ambroxol, the skilled artisan cannot envision the detailed chemical structure of the encompassed αSyn targeting agents, which are not limited to any type of structure, and may comprise a polypeptide, antibody, nucleic acid or small molecule Therefore, conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence. Therefore, only NPT200-11 and ambroxol, but not the full breadth of the claim meets the written description provision of 35 U.S.C. §112, first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
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 1-8 and 20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Poggiolini et al. (Biomolecules 2021, 11,820. https://doi.org/10.3390/biom11060820 —on IDS filed 12/01/2023). The effective filing date of the instant claims is 06/02/2021, and the publication date of Poggiolini et al. is 05/31/2021). Poggiolini et al. disclose a method for diagnosing a synucleinopathy in which samples containing αSynuclein (αSyn) were homogenized and centrifuged in TBS, which “represent[ed] the aqueous soluble fraction” followed by resuspension of the pellet in detergent, which represented the detergent-soluble fraction (see p. 3, 3rd paragraph). Purified full-length αSyn (1-140), as well as the truncated proteins, αSyn (1-115) and αSyn (1-130), were measured (see p. 3, last paragraph; p. 5, Figure 1b; p. 6, Figure 2). The truncated αSyn 1-130 in the detergent-soluble fraction was capable of distinguishing between Parkinson’s Disease (PD) and dementia with Lewy bodies (DLB) in the frontal cortex (see p. 5, Figure 1b; p. 7, last paragraph; p. 8, 1st paragraph).
Poggiolini et al. teach that the seeding activity was measured in brain lysates by the real-time quaking-induced conversion (RT-QulC) assay (see pages 3-4, under “2.4 RT-QuIC Assay). Poggiolini et al. disclose that “C-αSyn-130 is an attractive substrate for RT-QuIC assays. It differentiated DLB and PD from HC with 100% specificity and sensitivity using the TBS-soluble temporal cortex, and distinguished PD from DLB with 88% sensitivity and 100% specificity using the detergent-soluble frontal cortex” (see p. 8, 1st paragraph). Poggiolini et al. also teach that the C-αSyn-115 form induced a higher rate of seeding activity in the aqueous soluble fraction compared to the detergent soluble fraction compared to detergent soluble fraction in DLB samples (see p. 5, 1st paragraph; p. 6, 1st paragraph).
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 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over Poggiolini et al. in view of Krainc (US20140288093—on IDS filed 12/01/2023). 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. Poggiolini et al. disclose a method for diagnosing a synucleinopathy in which samples containing αSynuclein (αSyn) were homogenized and centrifuged in TBS, which “represent[ed] the aqueous soluble fraction” followed by resuspension of the pellet in detergent, which represented the detergent-soluble fraction (see p. 3, 3rd paragraph). Purified full-length αSyn (1-140), as well as the truncated proteins, αSyn (1-115) and αSyn (1-130), were measured (see p. 3, last paragraph; p. 5, Figure 1b; p. 6, Figure 2). The truncated αSyn 1-130 in the detergent-soluble fraction was capable of distinguishing between Parkinson’s Disease (PD) and dementia with Lewy bodies (DLB) in the frontal cortex (see p. 5, Figure 1b; p. 7, last paragraph; p. 8, 1st paragraph).
Poggiolini et al. teach that the seeding activity was measured in brain lysates by the real-time quaking-induced conversion (RT-QulC) assay (see pages 3-4, under “2.4 RT-QuIC Assay). Poggiolini et al. disclose that “C-αSyn-130 is an attractive substrate for RT-QuIC assays. It differentiated DLB and PD from HC with 100% specificity and sensitivity using the TBS-soluble temporal cortex, and distinguished PD from DLB with 88% sensitivity and 100% specificity using the detergent-soluble frontal cortex” (see p. 8, 1st paragraph). Poggiolini et al. also teach that the C-αSyn-115 form induced a higher rate of seeding activity in the aqueous soluble fraction compared to the detergent soluble fraction compared to detergent soluble fraction in DLB samples (see p. 5, 1st paragraph; p. 6, 1st paragraph).
The second factor to consider is to ascertain the differences between the prior art and the instant claims. Poggiolini et al. do not specifically disclose treating a diagnosed synucleinopathy, said treatment comprising administration of levodopa, for example. In addition, Poggiolini et al. do not disclose administering an anti-inflammatory or anti-oxidant. Nevertheless, Poggiolini et al. acknowledge the importance of developing therapeutics for PD and DLB (p. 12, 2nd paragraph). Further, Poggiolini et al. teach PD and DLB are characterized by “misfolding and aggregation of αSyn in neurons, neuronal processes, or glial cells” (see p. 1, 1st paragraph) and Krainc discloses “[g]enetic and histopathological evidence supports the idea that α-synuclein is the major component of several proteinaceous inclusions characteristic of specific neurodegenerative diseases” (see paragraph [0197]). Thus, the applied prior art provides a strong motivation for determining αSyn levels in diagnosing synucleinopathies.
Krainc discloses treatment of synucleinopathies, including PD and DLB with levodopa (see claims 75, 79; paragraphs [0212], [0459]-[0460]). In addition, Krainc discloses treatment with anti-inflammatory agents when inflammation is present (see paragraph [0470]). 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 Poggiolini et al. by treating PD and/or DLB, as taught in Krainc because both conditions require medication. The person of ordinary skill in the art would have been motivated to treat PD and DLB with known therapies because there is a general motivation to treat disease in the art. Furthermore, the person of ordinary skill in the art could have reasonably expected success because although levodopa and anti-inflammatories are not perfect treatments, they are routine medicaments when treating PD and DLB.
Thus, the claims do not contribute anything non-obvious over the prior art.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINA M BORGEEST whose telephone number is (571)272-4482. The examiner can normally be reached M-F 9-5:30 EDT.
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/CHRISTINA M BORGEEST/Primary Examiner, Art Unit 1675
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