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 .
Applicant's response to the previous Office action, dated June 3, 2026, has been received. By way of this submission, Applicant has amended claims 1, 25-28, 36, 39-41, 44-46, 48, 56-57, and 62-67, and cancelled claims 2-24, 29-35, 42, 43, 51-53, and 68-71.
Claims 1, 25-28, 36-41, 44-50, and 54-67 are pending in the application. Claims 25-27, 40-41, 44-50, 54-55, and 57-67 remain withdrawn from consideration, pursuant to the Restriction Requirement mailed July 14, 2025.
Claims 1, 28, 36-39, and 56 are therefore under examination before the Office.
The rejections of record can be found in the previous Office action, dated December 4, 2025.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on June 3, 2026 was filed after the mailing date of the first Office action on the merits on December 4, 2025. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Response to Amendment
Applicant argues that a person of skill in the art could not easily have conceived of the fusion protein of amended clam 1 in view of the recited references, as Figure 1B of Hishiya 2017 teaches that a fusion protein incorporating a J domain fragment of DNAJB1 is not as effective in enhancing target protein expression compared to J domain fragments from other J proteins such as DNAJC5 and SV40, and that Hishiya 2017 teaches J domain fusions with different technical effects. Applicant further argues that Aprile does not demonstrate that DNAJB6 interacts directly with alpha-synuclein. Applicant further argues that claimed fusion protein comprising a J domain and alpha-synuclein binding domain significantly reduced the aggregation of wildtype and mutant Syn(A53T) alpha-synuclein aggregation, which is an unexpected technical effect.
Applicant's arguments in view of the amendments to the claims have not addressed this issue fully. In the interest of compacting prosecution, the rejections under 35 U.S.C. 103 of claims 1, 3, 21, 36-39 and 56 over Hishiya 2017 (Sci Rep. 2017 Aug 17;7(1):8531, cited in IDS) in view of Arpile (Sci Rep. 2017 Aug 22;7(1):9039), claims 5-7 over Hishiya 2017 and Arpile as applied to claim 1 above, and further in view of Yarchoan (US20230173049A1), and claims 13-14, 22, 24, and 28 over Hishiya 2017, Arpile, and Yarchoan as applied to claim 1 above, and further in view of Cheruvara (J Biol Chem. 2015 Mar 20;290(12):7426-3 cited in IDS) are withdrawn. A new grounds of rejection is issued below, necessitated by Applicant's amendment to the claims.
Applicant further submits that the 18/033,454, 18/698,820, and 18/698,585 applicants have later filing dates than the instant application, and the outstanding double patenting rejections should be withdrawn pursuant to MPEP 804(I)(B)(1)(b)(i). As there are other rejections outstanding in the application, this argument is not persuasive.
The provisional double patenting rejections of claims 1, 28, 36-39, and 56 over claims 1, 3, 5-7, 20, 45 of application 18/033,454 in view of Arpile and Cheruvera, claims 1, 3, 5-7, 20, 57 of application 17/997,142 in view of Arpile and Cheruvera, claims 1, 5-6, 19, 62 of application 18/698,820 in view of Arpile and Cheruvera, and claims 1, 35, 48, 57-58, 76 of application 18/698,585 in view of Arpile and Cheruvera are therefore maintained.
In response to Applicant's arguments, a nonpreferred embodiment does not constitute a teaching away. A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989). "A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use." In re Gurley, 27 F.3d 551, 554, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994). MPEP 2123.
The technical effects of J domain fusions in correcting protein misfolding are taught by Arpile. Additionally, Hishiya 2017 also teaches J-domain fusion proteins may be useful for treating diseases of protein misfolding (page 9, fourth through sixth paragraphs).
There is nothing in the claims that requires that DNAJB6 interacts directly with alpha-synuclein, and even if there was, this is at best a latent property of the protein taught by the above references. Mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. In re Wiseman, 596 F.2d 1019, 201 USPQ 658 (CCPA 1979). Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). MPEP 2145(II).
With regards to Applicant's assertion of unexpected results, Arpile further teaches that the J domain of a J protein catalyzes the transfer of misfolded proteins to Hsp70, which rescues aggregation of alpha-synuclein (Figure 4 and page 5, third paragraph). For this reason, it would be expected that a J domain protein would be expected to rescue aggregation of alpha-synuclein, especially when combined with an alpha-synuclein targeting sequence, according to the teachings of Hishiya 2017 and Cheruvara.
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 § 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 28, 36-39, and 56 are rejected under 35 U.S.C. 103 as being unpatentable over Hishiya 2017 (Sci Rep. 2017 Aug 17;7(1):8531, cited in IDS) in view of Arpile (Sci Rep. 2017 Aug 22;7(1):9039), Yarchoan (US20230173049A1), and Cheruvara (J Biol Chem. 2015 Mar 20;290(12):7426-3 cited in IDS). This is a new grounds of rejection, necessitated by Applicant’s amendments to the claims.
Hishiya 2017 teaches a protein, comprising a J domain conjugated to a target protein-binding domain (page 1, last paragraph).
Hishiya 2017 teaches that this fusion protein is useful in treating diseases of protein misfolding (page 9, fourth through sixth paragraphs).
Hishiya 2017 also teaches a J domain sequence from human DnaJB1 (page 12).
Hishiya 2017 further teaches the above protein an in SDS buffer (i.e., a pharmaceutically acceptable buffer) (page 12, fourth paragraph), which is pertinent to claim 56.
However, Hishiya 2017 does not teach an alpha-synuclein-binding domain.
Arpile teaches that aggregations of misfolded alpha-synuclein are associated with Parkinson's Disease (page 1, first paragraph).
Arpile further teaches that the J domain of a J protein catalyzes the transfer of misfolded proteins to Hsp70, which rescues aggregation of alpha-synuclein (Figure 4 and page 5, third paragraph).
Yarchoan teaches a human DnaJB1 protein with a sequence of MGKDYYQTLGLARGASDEEIKRAYRRQALRYHPDKNKEPGAEEKFKEIAEAYDVLSDPRKREIFDRYGEEGLKGS, which completely encompasses Applicant's SEQ ID NO.: 5.
Cheruvara teaches the alpha-synuclein binding peptide KDGIVNGVKA (Figure 1), which is identical to Applicant's SEQ ID NO.: 51.
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the teachings of Hishiya 2017, Arpile, Yarchoan, and Cheruvara to arrive at the claimed invention. An ordinary artisan would have been motivated to do so, and have a reasonable expectation of success, since all of Hishiya 2017, Arpile, Yarchoan, and Cheruvara are concerned with treatments for diseases of protein misfolding. Starting with the protein of Hishiya 2017, one of ordinary skill could use an alpha-synuclein-binding domain as the target protein-binding domain according to the teachings of Arpile by simple substitution. Hishiya 2017 also teaches that human DnaJB1 is one such sequence that can be used in this context, and such a sequence is taught by Yarochan. Cheruvara also teaches a suitable alpha-synuclein-binding domain. One of ordinary skill in the art could apply the human DnaJB1 sequence of Yarchoan and the alpha-synuclein-binding domain of Cheruvara to the protein of Hishiya 2017 and Arpile by known methods to arrive at the claimed invention, with each component of the combination performing its known, usual function, and the combination would yield nothing more that predictable results.
With regards to claim 28, Applicant's SEQ ID NO.: 100 comprises the sequence of MGKDYYQTLGLARGASDEEIKRAYRRQALRYHPDKNKEPGAEEKFKEIAEAYDVLSDFRKREIFDRYGEEGLKGS, which is taught by Yarchoan, fused to the sequence of KDGIVNGVKA, which is taught by Cheruvara. Hishiya 2017 teaches fusions of DnaJ domains to a target binding sequence. Therefore, it would be obvious to assemble these sequences into a single peptide.
With regard to the claimed properties of claims 36-39, the fusion protein recited in the claims is the same as the protein of Hishiya 2017 and Arpile, and therefore would possess identical properties as those recited in claims 36-39. Hishiya 2017, Arpile, Yarchoan, and Cheruvara therefore inherently teach the subject matter of claims 36-39.
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, 28, 36-39, and 56 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 5-7, 20, and 57 of copending Application No. 17/997,142 in view of Arpile and Cheruvera.
The '142 application claims an isolated fusion protein comprising a J domain of a J protein and a TDP-43-binding domain (claim 1).
The '142 application further claims that the J domain of a J protein is of human origin (claim 3).
The '142 application further claims a J domain identical to that of Applicant's SEQ ID NO: 5 (claim 7).
The '142 application further claims that the DnaJ domain may be linked to the TDP-43 domain (claim 20).
The '142 application further claims a pharmaceutical composition, comprising the above fusion protein (claim 57).
However, the '142 application does not claim an alpha-synuclein binding domain.
Arpile teaches that aggregations of misfolded alpha-synuclein are associated with Parkinson's Disease (page 1, first paragraph).
Arpile further teaches that the J domain of the J protein DNAJB6 catalyzes the transfer of misfolded proteins to Hsp70, which rescues aggregation of alpha-synuclein (Figure 4 and page 5, third paragraph).
Cheruvara teaches the alpha-synuclein binding peptide KDGIVNGVKA (Figure 1), which is identical to Applicant's SEQ ID NO: 51.
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the claims of the '142 application with the teachings of Arpile and Cheruvara to arrive at the claimed invention. Starting with the protein claimed by the '142 application, one of ordinary skill could apply the alpha-synuclein-binding peptide of Cheruvara to arrive at the claimed invention. Motivation for such a combination can be found in Arpile, as Arpile teaches that J domains may rescue aggregation of alpha-synuclein, and in Cheruvara, as Cheruvara teaches that peptides that rescue aggregation of alpha-synuclein are useful in treating diseases such as Parkinson disease. Each component of the combination would perform its known, usual function, and the combination would yield nothing more than predictable results.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 28, 36-39, and 56 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 5-7, 20, and 45 of copending Application No. 18/033,454 in view of Arpile and Cheruvera.
The '454 application claims a fusion protein comprising a J domain of a J protein and a tau-binding domain (claim 1).
The '454 application further claims that the J domain of a J protein is of human origin (claim 3).
The '454 application further claims a J domain identical to that of Applicant's SEQ ID NO: 5 (claim 7).
The '454 application further claims that the DnaJ domain may be linked to the TDP-43 domain (claim 20).
The '454 application further claims a pharmaceutical composition, comprising the above fusion protein (claim 45).
However, the '454 application does not claim an alpha-synuclein binding domain.
Arpile teaches that aggregations of misfolded alpha-synuclein are associated with Parkinson's Disease (page 1, first paragraph).
Arpile further teaches that the J domain of the J protein DNAJB6 catalyzes the transfer of misfolded proteins to Hsp70, which rescues aggregation of alpha-synuclein (Figure 4 and page 5, third paragraph).
Cheruvara teaches the alpha-synuclein binding peptide KDGIVNGVKA (Figure 1), which is identical to Applicant's SEQ ID NO: 51.
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the claims of the '454 application with the teachings of Arpile and Cheruvara to arrive at the claimed invention. Starting with the protein claimed by the '454 application, one of ordinary skill could apply the alpha-synuclein-binding peptide of Cheruvara to arrive at the claimed invention. Motivation for such a combination can be found in Arpile, as Arpile teaches that J domains may rescue aggregation of alpha-synuclein, and in Cheruvara, as Cheruvara teaches that peptides that rescue aggregation of alpha-synuclein are useful in treating diseases such as Parkinson disease. Each component of the combination would perform its known, usual function, and the combination would yield nothing more than predictable results.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 28, 36-39, and 56 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 35, 48, 57-58, and 76 of copending Application No. 18/698,585 in view of Arpile and Cheruvera.
The '585 application claims a fusion protein comprising a J domain of a J protein and a target binding domain, wherein the target binding domain binds a protein associated with a neurodegenerative disease (claim 1).
The '585 application further claims a J domain identical to that of Applicant's SEQ ID NO: 5 (claim 35).
The '585 application further claims that the DnaJ domain may be linked to the target binding domain (claim 48).
The '585 application further claims that the fusion protein is capable of restoring the function of a target protein in a cell (claim 57).
The '585 application further claims that the fusion protein is capable of reducing misfolding of the target protein (claim 58).
The '585 application further claims a pharmaceutical composition, comprising the above fusion protein (claim 76).
However, the '585 application does not claim an alpha-synuclein binding domain.
Arpile teaches that aggregations of misfolded alpha-synuclein are associated with Parkinson's Disease (page 1, first paragraph).
Arpile further teaches that the J domain of the J protein DNAJB6 catalyzes the transfer of misfolded proteins to Hsp70, which rescues aggregation of alpha-synuclein (Figure 4 and page 5, third paragraph).
Cheruvara teaches the alpha-synuclein binding peptide KDGIVNGVKA (Figure 1), which is identical to Applicant's SEQ ID NO: 51.
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the claims of the '585 application with the teachings of Arpile and Cheruvara to arrive at the claimed invention. Starting with the protein claimed by the '585 application, one of ordinary skill could apply the alpha-synuclein-binding peptide of Cheruvara to arrive at the claimed invention. Motivation for such a combination can be found in Arpile, as Arpile teaches that J domains may rescue aggregation of alpha-synuclein, and in Cheruvara, as Cheruvara teaches that peptides that rescue aggregation of alpha-synuclein are useful in treating diseases such as Parkinson disease. Each component of the combination would perform its known, usual function, and the combination would yield nothing more than predictable results.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 28, 36-39, and 56 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5-6, 19, and 62 of copending Application No. 18/698,820 in view of Arpile and Cheruvera.
The '820 application claims a fusion protein comprising a J domain of a J protein and a protein binding domain (claim 1).
The '820 application further claims a J domain identical to that of Applicant's SEQ ID NO: 5 (claim 6).
The '820 application further claims that the DnaJ domain may be linked to the target binding domain (claim 19).
The '820 application further claims a pharmaceutical composition, comprising the above fusion protein (claim 62).
However, the '820 application does not claim an alpha-synuclein binding domain.
Arpile teaches that aggregations of misfolded alpha-synuclein are associated with Parkinson's Disease (page 1, first paragraph).
Arpile further teaches that the J domain of the J protein DNAJB6 catalyzes the transfer of misfolded proteins to Hsp70, which rescues aggregation of alpha-synuclein (Figure 4 and page 5, third paragraph).
Cheruvara teaches the alpha-synuclein binding peptide KDGIVNGVKA (Figure 1), which is identical to Applicant's SEQ ID NO: 51.
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the claims of the '820 application with the teachings of Arpile and Cheruvara to arrive at the claimed invention. Starting with the protein claimed by the '820 application, one of ordinary skill could apply the alpha-synuclein-binding peptide of Cheruvara to arrive at the claimed invention. Motivation for such a combination can be found in Arpile, as Arpile teaches that J domains may rescue aggregation of alpha-synuclein, and in Cheruvara, as Cheruvara teaches that peptides that rescue aggregation of alpha-synuclein are useful in treating diseases such as Parkinson disease. Each component of the combination would perform its known, usual function, and the combination would yield nothing more than predictable results.
This is a provisional nonstatutory double patenting rejection.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Gao (Mol Cell. 2015 Sep 3;59(5):781-93) teaches that DNAJB1 is useful for solubilizing fibrils of alpha-synuclein (page 9, last paragraph).
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PETER JOHANSEN whose telephone number is (571)272-0280. The examiner can normally be reached Monday-Friday, 7:00 to 3:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached at (571) 270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PETER JOHANSEN/Examiner, Art Unit 1644
/SAMIRA J JEAN-LOUIS/Supervisory Patent Examiner, Art Unit 1642
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