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 .
Response to Amendment
Applicant’s amendment filed 12/26/2025 is acknowledged. Claims 1-4, 9-12, 14 and 15 are amended; claims 5-8 and 13 are canceled and claims 19-21 are new. The previous indication of allowable subject matter in claims 3 and 9 at p. 3 of the Office action mailed 10/01/2025 is withdrawn upon further consideration, and a new rejection is made herein. This Office action is made non-final in order to give Applicant the opportunity to respond to the newly raised issue.
Claims 1-4, 9-12 and 14-21 are under examination.
Claim Interpretation
New claim 21 recites the judicial exception of comparing the level of circHOMER1 to a predetermined reference level (Prong One of Step 2A when considering patent eligibility under 35 USC 101). Nevertheless, claim 21, like claims 3 and 9, recites particular primers that were not routine in the detection of the encompassed circRNAs, and therefore, adds significantly more than the judicial exception.
Objections/Rejections Withdrawn
Any objections or rejections over claims 5-8 and 13 are hereby withdrawn in response to Applicant’s cancelation of those claims.
Claim Objections
The following objections for minor informalities in the claims have been addressed by Applicant’s amendment. Specifically, claim 9 has been amended to fix a typographical error. There is a remaining objection to claim 9 below. The objection to claim 12 is withdrawn in response to Applicant’s amendment deleting the redundant phrase.
Claim Rejections - 35 USC § 112(b)
The rejection of claim 11 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn in response to Applicant’s amendment. Specifically, claim 11 has been amended to clarify that that circDNAJC6 is increased relative to a reference.
Claim Rejections - 35 USC § 101
The rejection of claims 1, 2, 4, 10 and 11 under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more is withdrawn in response to Applicant’s amendment to affirmatively require treatment in the method claims.
Claim Rejections - 35 USC § 102
The rejection of claims 1, 4, 10 and 11 under 35 U.S.C. 102(a)(1) as being anticipated by Rajewsky et al. (WO2017/055487) is withdrawn in response to Applicant’s amendment. Specifically, the claims now require measuring cirHOMER1 and treatment, which Rajewsky et al. do not disclose.
Claim Rejections - 35 USC § 103
The following rejections under 35 U.S.C. 103 are hereby withdrawn in response to Applicant’s amendments to the claims to require both reduced or lower levels of circHOMER1 and methods of treatment together in the independent claims.
Claims 1, 2, 4-6, 8, 10 and 11 as being unpatentable over Rajewsky et al. (WO2017/055487) in view of Dube et al. (Alzheimer's and Dementia, (July 2018) Vol. 14, No. 7, Supp. Supplement, pp. P1401. Meeting Info: Alzheimer's Association International Conference 2018. Chicago, Illinois, United States. 22 Jul 2018-26 Jul 2018).
Claims 1, 4, 5, 8, 10-12 and 14-18 as being unpatentable over Rajewsky et al. (WO2017/055487) in view of Gervais (WO2004058258).
Claims 2, 5, 6 and 13 as being unpatentable over Rajewsky et al. (WO2017/055487) and Gervais (WO 2004058258) as applied to claims 1, 4, 5, 8, 10-12 and 14-18 above, and further in view of Dube et al. (Alzheimer's and Dementia, (July 2018) Vol. 14, No. 7, Supp. Supplement, pp. P1401. Meeting Info: Alzheimer's Association International Conference 2018. Chicago, Illinois, United States. 22 Jul 2018-26 Jul 2018).
Objections Maintained/New Objection/Rejection
Specification
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed.
The following title is suggested: METHODS OF DETECTING CIRCRNA ASSOCIATED WITH ALZHEIMER’S DISEASE.
Claim Objections
Claims 1, 12 and 20 are objected to because of the following informalities.
(i) The comma in claim 1, line 8, after “reference level” should be deleted.
(ii) In claim 12, line 7, the indefinite article “a” should be inserted before “level”. In addition, the recitation in line 8 “is indicative that the subject is having” is grammatically awkward. The verb form “is having” should be replaced by “has”.
(iii) Claim 20 recites “[a] method of Alzheimer’s disease” followed by an administration step (“comprising administering”), strongly suggesting that Applicant inadvertently left out the verb “treating” following “method” in line 1.
Appropriate correction is required.
New Rejection
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, 9-12 and 14-20 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 claims contain 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.
The claims are drawn to methods of treating Alzheimer’s disease in a subject who is asymptomatic or presymptomatic as indicated by reduced levels of circHOMER1 comprising administering a laundry list of agents that includes a passive immunotherapy, an active vaccine, a kinase inhibitor, a phosphatase activator, a phosphatase inhibitor and a microtubule protein modulator. The specification does not indicate which kinase or phosphatase is inhibited or activated. The specification provides two examples of an active vaccine, namely, CAD106, and AF20513 (see paragraph [00127]), both of which induce amyloid-beta antibody production. In addition, the specification does not disclose the type of agent contemplated for “passive immunotherapy”. Assuming that an antibody is contemplated, the specification does not disclose the target (antigen) such an antibody is directed against. Claims 12 and 19 also recite that the pharmaceutical composition that is administered “correct or stabilize the differentially expressed” circRNA.
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, applicant was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc., 935 F.2d at 1563-64, 19 USPQ2d at 1117. The factors to be considered when analyzing claims for compliance with the written description requirement include: actual reduction to practice; disclosure of drawings or structural chemical formulas; sufficient relevant identifying characteristics (e.g., disclosure of complete or partial structure, physical and/or chemical properties, structure/function correlation); method of making the claimed invention; level of skill and knowledge in the art; and predictability in the art. 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)).
The categories of active vaccines, kinase inhibitors, phosphatase activators and phosphatase inhibitors are known generally, but in the instant case, the claims recite functionally-claimed agents with no disclosure of any relevant structures capable of treating Alzheimer’s disease and correcting or stabilizing differentially expressed circRNA. Regarding the phosphatase activators, the reference by Bownes et al. (J Pediatr Surg. Author manuscript; available in PMC: 2024 Jun 1) teaches that fingolimod activates protein phosphatase 2A, and that other activators are being developed (see p. 2, last paragraph). Nevertheless, Bownes et al., published four years post-filing, teach only one type of phosphatase for the development of activators. Similarly, Swingle (Curr Med Chem. 2019; 26(15): 2634-2660. doi:10.2174/0929867325666180508095242) teaches that while phosphatase inhibition may be a worthy goal in cancer treatment, “developing PPPase [PPP-family phosphatases] inhibitors into drugs will be challenging because as discussed above the PPP-family phosphatases share a catalytic mechanism, and many family members retain a high degree of structural similarity in the regions surrounding the active site” (see p. 2643, right column, 1st full paragraph). The PPPases represent a single category of serine/threonine phosphatases, but there are dozens of phosphatases (see Chen et al., Sci. Signal. 10, eaag1796 (2017) at p. 1, right column, last paragraph). Regarding kinases, while there are at least 20 mostly cancer drugs that have been developed that target protein kinases, there are 518 different kinases (see Swingle, p. 2643, right column, 1st full paragraph and Bhanumathy et al., Cancers 2021, 13, 184. https://doi.org/10.3390/ cancers13020184, especially abstract; p. 2; 1st paragraph). In summary, the genus of the encompassed active vaccines, phosphatase inhibitors/activators and kinase inhibitors is vast, but with no corresponding structure to function (treating Alzheimer’s disease) correlation.
Regarding antibodies, a single example of a type of passive immunotherapy, the Federal Circuit has clarified Written Description as it applies to antibodies in Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017). The Federal Circuit explained in Amgen that when an antibody is claimed, 35 U.S.C. 112(a) (or pre-AIA first paragraph) requires adequate written description of the antibody itself. Amgen, 872 F.3d at 1378-79. The Amgen court expressly stated that the so-called “newly characterized antigen” test, which had been based on an example in USPTO-issued training materials and was noted in dicta in several earlier Federal Circuit decisions, should not be used in determining whether there is adequate written description under 35 U.S.C. 112(a) for a claim drawn to an antibody. Citing its decision in Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., the court also stressed that the “newly characterized antigen” test could not stand because it contradicted the quid pro quo of the patent system whereby one must describe an invention in order to obtain a patent. Amgen, 872 F.3d at 1378-79, quoting Ariad, 598 F.3d 1336, 1345 (Fed. Cir. 2010). In view of the Amgen decision, adequate written description of a newly characterized antigen alone is not considered adequate written description of a claimed antibody to that antigen, even when preparation of such an antibody is routine and conventional. Id.
The recitation of a passive immunotherapy capable of treating Alzheimer’s disease represents functional characteristics with limited structure. While the generic structure of antibodies is known, the specification does not disclose the structure of the encompassed antibodies. The genus of antibodies is vast, but with no corresponding structure to function (treating Alzheimer’s disease) correlation. The relevant art recognizes that diversity of antibodies binding to any particular target antigen or epitope is extremely broad, and therefore there is no way to reasonably predict the structure of the antigen-binding region of an antibody even if the antigen or epitope were known (see, for example, Lloyd et al. Protein Eng. Design & Select, 2009, 22(3):159-168; and Edwards et al. J. Mol. Biol. 2003, 334:103-118). Consequently, in the absence of sufficient recitation of distinguishing identifying characteristics of the encompassed molecules and in light of the unpredictable nature of designing such molecules, the specification does not provide adequate written description of the claimed genus nor guidance as to which of the myriad of molecules encompassed by the recited passive immunotherapy, kinase inhibitor, phosphatase activator, phosphatase inhibitor would meet the limitations of the claims.
Functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. Abbvie Deutschland GMBH & Co. v. Janssen Biotech, Inc. (Fed. Cir. 2014, Appeal No. 13-1338 at page 26). Therefore, the full breadth of the claims does not meet the written description provision of 35 U.S.C. 112(a). Applicants are reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. 112(a) is severable from its enablement provision.
Conclusion
Claims 1-4, 9-12 and 14-20 are rejected and claim 21 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