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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 6/04/2026 has been entered.
Claims 1, 23-24, 26-28, 30, 32-33 and 35 are currently pending.
Claims 26-28, 30, 32-33 and 35 are withdrawn from consideration as being drawn to a non
elected invention.
In the response to the species requirement of 5/28/2025, Applicants elected the following species:
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which reads on amended claim 1. The examiner expanded the election to encompass structurally similar compounds found in the prior art as set forth below.
Claims 1 and 23-24 are currently under consideration.
Rejections Maintained, but amended in view of Applicants amendment:
Claim Rejections - 35 USC § 103
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.
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.
Claim(s) 1 and 23-24 remain rejected under 35 U.S.C. 103 as being unpatentable over Dana-Farber Cancer Institute (WO2019/014429A1, 2019-01-17, IDS) referred to herein as Dana in view of Higuchi et al. (US2015/0239878A1, 2015-08-27, IDS).
Dana teaches compounds of Formula I: T-L-E, wherein T is a tau protein binding moiety, E is an E3 ubiquitin binding moiety and L is a substituted or unsubstituted alkylene, substituted or unsubstituted alkenylene, substituted or unsubstituted alkynylene, substituted or unsubstituted arylene, substituted or unsubstituted heterocyclylene, substituted or unsubstituted arylene, substituted or unsubstituted heteroarylene, substituted or unsubstituted heteroalkylene, a bond or a variety of substituted heteroatoms (paragraph 00121). With regards to T, the WO document teaches that T includes, but is not limited to,
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which reads on the instantly claimed Tau targeting ligand (page 66). Moreover, the WO document teaches that compounds having the following formulas wherein T is a tau targeting moiety and q is 1-6 or 1-4:
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,
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,
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,
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,
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,
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which read on the instantly claimed Linker and Degron (claims 46-53 of the WO document). Moreover, the WO document teaches a pharmaceutical composition comprising the compound and a pharmaceutically acceptable excipient (claim 57 of the WO document). With regards to the pharmaceutical composition, the WO document teaches that the pharmaceutical composition is in the form of a solid or a liquid (paragraph 00373).
While Dana contemplates targeting moieties having the structure
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, Dana does not specifically select a targeting moiety having said structures. Nor does Dana teach wherein q is as recited in claim 1 of the instant application.
Higuchi et al. teach compounds that can specifically bind to Tau aggregates having the formula
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, wherein ring A is a benzene ring or pyridine and ring B has the formula
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(paragraphs 0012-0017). In particular, the PG Publication teaches specific compounds encompassed by formula I including, but not limited to, a compound referred to as PBB3 having the structure:
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which bound strongly with NFT’s in the AD patient’s hippocampus (paragraph 0083, Table 1, and paragraph 0428).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to modify compound taught by Dana to include a Tau targeting compound having the formula
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in view of the teachings of Higuchi et al.. One of ordinary skill in the art would have been motivated to make such a modification, with a reasonable expectation of success, because:
-Higuchi et al. teach a structurally similar compound having high affinity for NFT’s in AD patient’s hippocampus.
Moreover, it would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to modify the linker within the compound taught by Dana to include 2, 3, 4 or 5 methylene or methoxy groups. One would have been motivated to do so because compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). Accordingly, it would appear that the specific compounds claimed in claim 22 of the instant application are obvious over the combination for the reasons set forth above.
In response to this rejection, Applicants contend that Dana-Farber fails to disclose any molecules with a tau targeting ligand further comprising an alkylene-amide or PEG amide linker. Moreover, Applicants contend that in order to arrive at the claims as amended, Dana-Farber would have to select a specific tau targeting ligand from over two dozen, a linker that was an alkylene-amide linker or PEG-amide linker out of a near infinite number of linkers, wherein there is no motivation or suggestion that these linkers are superior to any other linkers especially with the specific tau targeting ligand described by the examiner. Applicants further contend that Huguchi does not remedy the deficiencies of Dana-Farber. Lastly, Applicants contend that the results shown by compounds within the scope of the claims as amended are unexpected, as shown in Example 7, wherein the compounds within the scope of the claims are useful for degrading tau protein in cultured human differentiated frontotemporal dementia neurons. By contrast, Applicants contend that neither Dana-Farber nor Higuchi provide evidence that compounds falling within the scope of the claims would be effective at degrading tau protein.
These arguments have been carefully considered, but are not found persuasive.
In response to Applicants arguments pertaining to the teachings of Dana-Farber, the Examiner acknowledges that the WO document does not specifically provide an example of a tau targeting ligand further comprising an alkylene-amide or PEG amide linker. However, the examiner recognizes that Dana-Faber does contemplate a Tau targeting ligand such as
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, as well as, provides a number of compounds having an alkylene-amide linker linked to the degrader such as
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, wherein T is the targeting ligand (see for example, claim 51 of the WO document). Specific selection of the T comes from the teachings of Huguchi as described above. Regarding Applicants assertion of unexpected results, the Examiner has reviewed example 7 of the specification and cannot find any specific recitation of “surprising” or “unexpected” and Applicants have not specifically pointed out how or why the results of Example 7 are truly unexpected. "[A]ppellants have the burden of explaining the data in any declaration they proffer as evidence of non-obviousness." Ex parte Ishizaka, 24 USPQ2d 1621, 1624 (Bd. Pat. App. & Inter. 1992). See MPEP 716.02 (b). Application are reminded that [A]rguments presented by the applicant cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965) and In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984). Examples of statements which are not evidence and which must be supported by an appropriate affidavit or declaration include statements regarding unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the inventor or at least one joint inventor. In the instant case, the Examiner recognizes that Dana et al. teach that the Tau portion of the molecules is the targeting moiety and the compound having in the structure I-1 above is the degron. As such, it is would be reasonably expected that degradation of Tau protein would occur.
Conclusion
Therefore, No claim is allowed.
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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 BRANDON J FETTEROLF whose telephone number is (571)272-2919. The examiner can normally be reached M-F 6AM-4PM.
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, Jeffrey S Lundgren can be reached at 571-272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BRANDON J FETTEROLF/Primary Examiner, Art Unit 1626
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