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 .
DETAILED ACTION
RESPONSE TO AMENDMENT
Status of Application/Amendments/claims
2. Applicant’s amendment filed October 1, 2025 is acknowledged. Claims 8 and 16-32 are canceled. Claims 1-4, 6-7, 9, 11 and 14 are amended. Claims 1-7 and 9-15 are pending in this application. Election was made without traverse in the reply filed on March 10, 2025.
3. Claims 1-7 and 9-15 are under examination in this office action.
4. Applicant’s arguments filed on October 1, 2025 have been fully considered but they are not deemed to be persuasive for the reasons set forth below.
Specification
5. The objection to the specification is withdrawn in response to Applicant’s amendment to the specification.
Claim Rejections/Objections Withdrawn
6. The objection to claims 1 and 16 is withdrawn in response to Applicant’s amendment to the claims and cancelation of claim 16.
The rejection of claims 4, 9, 14 and 19 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn in response to Applicant’s amendment to the claims and cancelation of claim 19.
The rejection of claims 8 and 16-20 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, lack of scope of enablement is moot because the claims are canceled.
The rejection of claims 8 and 16-20 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 is moot because the claims are canceled.
Claim Rejections/Objections Maintained
In view of the amendment filed on October 1, 2025, the following rejections are maintained.
Claim Rejections - 35 USC § 112
7. 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 1-7 and 9-15 stand rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for reducing aggregation of TDP-43ΔNLS in 293T cells that are transfected with an inducible TDP-43 aggregating construct of TDP-43ΔNLS (293T-TDP-43ΔNLS cells) by transfecting the 293T-TDP-43ΔNLS cells with an expression construct encoding SRRD (SEQ ID NO:1) or the N-terminal Arg-rich LCD of SRRD (i.e. aa 1-50 of SEQ ID NO:1) compared to control 293T-TDP-43ΔNLS cells without transfection or reducing toxicity induced by TDP-43, alpha-synuclein or FUS in yeast cells that express TDP-43, alpha-synuclein or FUS by transfecting the yeast cells with an expression construct encoding SRRD (SEQ ID NO:1) compared to control yeast without transfection, does not reasonably provide enablement for methods of reducing all forms of protein aggregation in a cell in vitro or in vivo including all possible conditions by providing to a cell the claimed active fragment comprising residues 1-50 of SEQ ID NO:1 or an expression construct encoding the claimed active fragment thereof as broadly claimed. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. The rejection is maintained for the reasons of record and the reasons set forth below.
Claims 1-7 and 9-15 as amended are drawn to a method of reducing all forms of protein aggregation in a cell including in vitro and in vivo, comprising providing to a mammalian cell or yeast cell an active fragment of SSRD comprising residues 1-50 of SEQ ID NO:1 or an expression construct encoding the claimed active fragment thereof.
Response to Arguments
On p. 5-6 of the response, Applicant argues that the rejection has been overcome in view of amendment to the claims by defining the SRRD as an active fragment comprising residues 1-50 of SEQ ID NO:1 and limiting the claims to mammalian or yeast cells and eliminating the disease therapy.
Applicant's arguments have been fully considered but they are not found persuasive. Contrary to Applicant's arguments, the examiner asserts that based on MPEP §2164, MPEP §§2164.01-2164.06(b) & 2164.08, the specification provides insufficient guidance to enable a skilled artisan to practice the full scope of the claimed invention without undue experimentation because:
i. Claims 1-7 and 9-15 as amended encompass reducing all forms of protein aggregation in vitro and in vivo in all possible conditions by the claimed active fragment comprising residues 1-50 of SEQ ID NO:1 or an expression construct thereof.
Claim 15 is directed to a method of reducing protein aggregation in a living mammal using the claimed active fragment because claim 15 recites “wherein said cell is a mammalian cell and is located in a living mammal including living mammals with all possible conditions.
ii. The specification provides no well-established correlation between the in vitro cell model of specific protein aggregation caused by TDP-43ΔNLS in 293T-TDP-43ΔNLS cells or toxicity caused by TDP-43, alpha-synuclein or FUS in yeast cells overexpressing TDP-43, alpha-synuclein or FUS and different forms of protein aggregation in vitro or in vivo, or in different diseases associated with different forms of protein aggregation.
As previously made of record, the causes of different forms of protein aggregation or different protein aggregation diseases including all forms of AD, PD, ALS or FTD are different. For example, several genes have been found to be associated with familial ALS, including SOD1, TARDBP, FUS, UBQLN2, PFN1, OPTN, VCP, MATR3, TUBA4A, C9ORF72, NEK1, KIF5A, VCP, ALS2, SETX, ANG, CHCH10, SQSTM1, TBK1 and CCNF as taught by Williams et al. (Nat. Commun. 2016;7:11253. DOI:10.1038/ncomms11253, cited previously), Ranganathan et al. (Front. in Neurosci. 2020; doi:10.3389/fnins.2020.00684, cited previously) and Bruijn et al. (Annu. Rev. Neurosci. 2004, 27: 723-49, cited previously). While mutations in SOD-1, TARDBP, FUS/TLS and CCNF have been identified and considered as causative for familial ALS, the pathogenesis of ALS is multifactorial. TDP-43 aggregates can only be found in sporadic ALS patients. The pathogenesis mechanisms for different forms of ALS are independent and distinct from each other as evidenced by Ju et al. (PLoS Biology 2011; 9: 1-17; e1001052, cited previously) and Lagier-Tourenne et al. (see table 1, Human Mol. Genet. 2010; 19: R46-R64, cited previously).
The in vitro data in examples only showed reducing aggregation of TDP-43ΔNLS in 293T-TDP-43ΔNLS cells or reducing toxicity caused by overexpression of TDP-43, alpha-synuclein or FUS. There is no nexus or correlation between protein aggregation caused by TDP-43ΔNLS in 293T-TDP-43ΔNLS cells or toxicity caused by TDP-43, alpha-synuclein or FUS in yeast cells overexpressing TDP-43, alpha-synuclein or FUS and different forms of protein aggregation in vitro or in vivo, or in different diseases associated with different forms of protein aggregation. There is no correlation between reducing protein aggregation caused by TDP-43ΔNLS in 293T-TDP-43ΔNLS cells by the claimed active fragment and other genes/mechanisms involved in different forms of protein aggregation or the pathogenesis of different protein aggregation diseases including all forms of AD, PD, ALS or FTD that are not associated with TDP-43ΔNLS, TDP-43, alpha-synuclein or FUS. Thus, it is unpredictable whether administration of the claimed active fragment or an expression construct thereof can reduce different forms of protein aggregation or the pathogenesis of different protein aggregation diseases including all forms of AD, PD, ALS or FTD that are not associated with TDP-43ΔNLS, TDP-43, alpha-synuclein or FUS, indicating undue experimentation is required by a skilled artisan to perform while practicing the claimed invention.
iii. The specification also provides no well-established correlation between reducing aggregation of TDP-43ΔNLS in 293T-TDP-43ΔNLS cells transfected with an expression construct encoding SRRD of SEQ ID NO:1 or the N-terminal SRRD of aa 1-50 of SEQ ID NO:1 or reducing toxicity caused by TDP-43, alpha-synuclein or FUS in yeast cells and reducing all forms of protein aggregation in vitro or in vivo including all forms of protein aggregation diseases in vivo by the claimed active fragment comprising residues 1-50 of SEQ ID NO:1 without any specific targeting moiety to enter the nucleus or cytoplasm of the cell in vitro or in vivo or all forms of protein aggregation diseases in vivo. It is unpredictable whether providing the claimed active fragment with no specific targeting moiety can enter the nucleus or cytoplasm of the cell to reduce aggregation caused by TDP-43, or toxicity caused by alpha-synuclein or FUS or even to reduce all forms of protein aggregation in vitro and in vivo or in all possible conditions in vivo. Thus, the skilled artisan cannot contemplate how to make and use the claimed method without undue experimentation.
Note that the scope of the claims must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1970)). Without such guidance, it is unpredictable whether other forms of protein aggregations can be reduced or whether protein aggregations in different diseases can be treated by the claimed active fragment; and thus the experimentation left to those skilled in the art is extensive and undue. See Ex parte Forman, 230 USPQ 546 (Bd. Pat. App. & Int. 1986). Thus, the skilled artisan cannot readily know how to use the claimed invention as currently claimed without further undue experimentation. In re Marzocchi, 439 F.2d 220, 223-24,169 USPQ 367, 369-70 (CCPA 1971)” See MPEP § 2164.03.
Therefore, in view of the breadth of the claims, the lack of guidance in the specification, no working examples, the unpredictability of inventions, and the current status of the art, undue experimentation would be required by a skilled artisan to perform in order to practice the claimed invention as it pertains to a method of reducing protein aggregation in a cell by the claimed active fragment.
Accordingly, the rejection of claims 1-7 and 9-15 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, lack of scope of enablement is maintained.
Claim Rejections - 35 USC § 112
8. Claims 1-7 and 9-15 stand 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 rejection is maintained for the reasons of record and the reasons set forth below.
Claims 1-7 and 9-15 as amended encompass using the claimed active fragment comprising residues 1-50 of SEQ ID NO:1 or an expression construct encoding the claimed active fragment thereof for reducing a genus of protein aggregation in a mammalian cell or yeast cell in vitro and in vivo including all possible conditions.
Applicant has not disclosed sufficient species for the broad genus of protein aggregation reduced by the claimed active fragment or an expression construct thereof.
Response to Arguments
On p. 5-6 of the response, Applicant argues that the rejection has been overcome in view of amendment to the claims by defining the SRRD as an active fragment comprising residues 1-50 of SEQ ID NO:1 and limiting the claims to mammalian or yeast cells and eliminating the disease therapy.
Applicant's arguments have been fully considered but they are not found persuasive. Contrary to Applicant's arguments, the examiner asserts that based on MPEP §2163, MPEP §§2163.01-2163.03, the specification fails to provide sufficient description or information or evidence to demonstrate that Applicant is in possession of the claimed method of reducing the claimed genus of protein aggregation in vitro or in vivo including all possible conditions because:
i. Claims 1-7 and 9-15 as amended encompass reducing a genus of protein aggregation in vitro and in vivo including all possible conditions by the claimed active fragment comprising residues 1-50 of SEQ ID NO:1 or an expression construct thereof.
ii. There is no well-established correlation between the in vitro cell model of specific protein aggregation caused by TDP-43ΔNLS in 293T-TDP-43ΔNLS cells or toxicity caused by TDP-43, alpha-synuclein or FUS in yeast cells overexpressing TDP-43, alpha-synuclein or FUS and different forms of protein aggregation in vitro or in vivo, or in different diseases associated with different forms of protein aggregation.
iii. There is no well-established correlation between reducing aggregation of TDP-43ΔNLS in 293T-TDP-43ΔNLS cells transfected with an expression construct encoding SRRD of SEQ ID NO:1 or the N-terminal SRRD of aa 1-50 of SEQ ID NO:1 or reducing toxicity caused by TDP-43, alpha-synuclein or FUS in yeast cells and reducing all forms of protein aggregation in vitro or in vivo including all forms of protein aggregation diseases in vivo by the claimed active fragment comprising residues 1-50 of SEQ ID NO:1 without any specific targeting moiety to enter the nucleus or cytoplasm of the cell in vitro or in vivo or all forms of protein aggregation diseases in vivo.
The instant specification fails to provide sufficient descriptive information, such as definitive structural or functional features of the claimed genus of protein aggregation. There is no information regarding the relation of the structure of other forms of protein aggregation to the function of protein aggregation caused by TDP-43ΔNLS in 293T-TDP-43ΔNLS cells or toxicity caused by TDP-43, alpha-synuclein or FUS in yeast cells overexpressing TDP-43, alpha-synuclein or FUS. Furthermore, the prior art does not provide compensatory structural or correlative teachings sufficient to enable one of skill to identify what other forms of protein aggregation might be. Since the common characteristics/features of other forms of protein aggregation are unknown, a skilled artisan cannot envision the functional correlations of the genus with the claimed invention. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the genus of undefined protein aggregation.
Based on MPEP § 2161.01 and §2163, “to satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116”.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “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).
As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of undefined protein aggregation, and 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.
Therefore, the claimed method has not met 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). Applicant is directed to the Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, ¶ 1 "Written Description" Requirement. See MPEP § 2161.01 and 2163.
Accordingly, the rejection of claims 1-7 and 9-15 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 is maintained.
Conclusion
9. NO CLAIM IS ALLOWED.
10. THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Chang-Yu Wang whose telephone number is (571)272-4521. The examiner can normally be reached on Monday-Thursday, 7:00am-5:30pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker, can be reached on 571-272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Chang-Yu Wang
January 27, 2026
/CHANG-YU WANG/Primary Examiner, Art Unit 1675