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
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 4DEC2025 has been entered.
Claims Pending 1,3,5-8,13-18,28-34
Claims Under Consideration 1,3,5-8,13-18,28-34
Priority
This application has a filing date of 6/22/2023 with no earlier priority documents.
Withdrawn Rejection
The rejection of claims 1,3,5-8,13-18 under 35 U.S.C. 102(a)(2) as being anticipated by Kojima et al (US PG-Pub 20240069033) is hereby withdrawn in view of Applicant’s amendments.
Maintained 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.
Claims 1,3,5-8,13-18 and 28-30 plus 31-34 are rejected under 35 U.S.C. 103 as being unpatentable over Kojima et al (US PG-Pub 20240069033; of record) in view of Han et al (2017 Science vol 356 eaal3755 13 pages; of record) with evidence provided by BioTek provided as an appendix to this action.
Kojima et al teach throughout the document and especially at least paragraphs 0003,0012,0015,0028 [method 61],0058 [method 78] and/or 0183, 0074,0180, 0135, evaluating protein-protein interactions (PPIs) with proximity assays based on split GFP (green fluorescent protein) complementation. More particularly in the passages, Kojima et al: (1) provides an assay mixture with:various candidate compound molecules, first protein molecules such as FKBP or ubiquitin E3 ligase that targets proteins for degradation and are covalently attached to a GFP10 first fragment and optionally an affinity component; and second protein molecules such as calcineurin or others covalently attached a GFP11 second fragment and a detector GFP fragment that complements the first and second GFP fragments and comprises GFP1-9, wherein the first and second tag (GFP fragments) plus detector generate or enhance an assay signal from the assay mixture arising from a complex of the first protein, the second protein and a compound; then optionally (2A) contacts the complex with an immobilized affinity binder targeting the affinity component, thereby forming an immobilized complex and/or finally (2B) detects and/or isolates the complex and thereby identifies the first protein, the second protein and/or the compound as associated with formation of such complex by fluorescence. In paragraphs 0123 and 0222, Kojima et al suggest untagged candidate compounds may be identified by affinity selection mass spectrometry (ASMS) as well as employing enhanced GFP (EGFP) that inherently has excitation and emission wavelengths of 488 and 509 nm respectively (as indicated by BioTek). The foregoing reads on claims 1,3,5,6,7,8,13,14,15,16,17,18,31 & 33.
Kojima et al do not teach: a compound identified as capable of causing the degradation of a first protein in the presence of a second protein by modulating a PPI that is administered to a subject to treat disease per claims 28-30.
Like claims 28,29 & 30 - applicant’s own publication - Han et al teach throughout the paper and especially the abstract and figure 1H, the aryl sulfonamide indisulam as an anticancer sulfonamide drug that acts as a molecular glue, targeting proteasomal degradation of a first protein (e.g. RBM39) in the presence of E3 ubiquitin ligase by modulating a PPI that is administered to a mouse experimental subject.
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have utilized the split GFP complementation technique advocated by Kojima et al for evaluating the specificity of indisulam for other proteins (in other cancer cell pathways), or else develop more a specific sulfonamide for the benefit of minimizing side-reactions, the former motivation being alluded to by Han et al in the last sentence of the text.
One of ordinary skill in the art would have had a reasonable expectation of success in developing sulfonamides targeting other pathways important for cancer proliferation with the split GFP proximity assays of Kojima et al since any cellular protein is susceptible to proteasomal destruction.
Concerning claims 32,34 and claims 1 and 3 when drawn to deconvolution, please note the test for obviousness is not that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
Here, paragraphs 0483-0485 of the present published application define deconvolution as when an individual POI (protein of interest; target; e.g. RBM39), a E3 (ubiquitin ligase), and potential glue compound (candidate molecular glue) are tested in such a way (including mass spectrometry) to uniquely and unambiguously identify which specific combination leads to a POI glued to E3. For example, as disclosed in Han figure 5B and discussed in the center column of p 6, the same POI and E3 mixture can be tested against individual compounds in an active pool for identification of the active glue molecule Therein, Han et al further disclose two other molecular glues, tasisulam and CQS (molecular glues) that target RBM39 to E3 like indisulam, Each of indisulam, tasisulam and CQS have a different molecular weight, thus alternatively deconvoluting a pool of molecular glues may be handily done my mass spectrometry including Kojima’s ASMS.
Response to Arguments
The remarks accompanying the current response argue (a) not all elements are taught and (b) motivation to combine is lacking.
Applicant’s arguments have been fully considered but they are not deemed persuasive for the following reasons.
More particularly concerning (a) pp 6-7 of the remarks allege Kojima et al is silent regarding: compound identification with mass spectrometry or deconvolution; and irradiation with 488 nm light set forth in amended claims 1 and 3.
In this vein, as detailed supra, Applicant’s attention is respectfully invited to paragraph 0123, where Kojima et al expressly disclose candidate molecule identification by mass spectrometry and paragraph 0222 where Kojima suggest EGFP (enhanced green fluorescent protein) that is inherently excited by 488 nm then emits 509 nm light as shown in BioTek.
Regarding (b), p 7 of the remarks again contends motivation is lacking because Kojima teaches away from the presently claimed invention in paragraph 0012, describing fluorescence detection as “…laborious, costly and limits the numbers of test molecules that can be handled.”, allegedly disparaging fluorescence and urges Kojima relies on nucleic acid tagging of candidate compounds.
In response reiterating from the last action, first, as interpreted in MPEP 2123 I, under Celeritas Technologies Ltd. v. Rockwell International Corp., 150 F.3d 1354, 1361, 47 USPQ2d 1516, 1522-23 (Fed. Cir. 1998), the court held that "The fact that a modem with a single carrier data signal is shown to be less than optimal does not vitiate the fact that it is disclosed.", that is prior art will anticipate claims even when it teaches away from the claimed invention. Likewise, here even assuming arguendo that Kojima et al disparages fluorescence detection, the fact that fluorescence is less optimal does not vitiate the fact that it is disclosed. Indeed, as in paragraph 0028 method [61] GFP complementation requires fluorescence detection.
Second taken in context, Kojima et al states “…in the case of fluorescence detection, a target molecule and a single candidate molecule are required… which is laborious and costly, and limits the number of test molecules that can be handled” (emphasis added). In other words, while detection with fluorescence may reduce throughput in libraries with large numbers of compounds according to Kojima et al, one motivation with Han et al concerns only four drug candidate aryl sulfonamides targeting ubiquitin ligase mediated degradation of proteins beyond RBM39. In contrast with Applicant’s argument, 4 spit GFP complementation experiments (deconvolution using the same POI and E3 mixture tested against individual glue candidates as in paragraph 0483 of the present published application) induced by each compound would not be particularly burdensome or costly and Kojima et al does not disparage fluorescence for such experiments, nor are large numbers of candidate compounds recited in the present claims.
Finally, even assuming arguendo that Han et al taught a large number of candidate molecular glues, such as to improve specificity such as for the second motivation identified in the rejection above and identification by fluorescence alone of would indeed be time consuming, as mentioned above, in paragraph 0123, Kojima suggests affinity selection by mass spectrometry as an alternative for untagged candidate compounds that does not rely on nucleic acid tags and can identify (deconvolute) hundreds of thousands of compounds in a few days)
In conclusion, Kojima et al does not teach away from fluorescence detection nor deconvolution by mass spectrometry and in fact, teaches toward both techniques, especially when working with compounds lacking nucleic acid tags
Claim Rejection(s) – 35 USC § 112
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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 1,3,5-8,13-18,28-34 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This rejection concerns new matter.
Claims 1 and 3 and new claims 31-32,34 introduce: irradiating a ternary split GFP complementation protein proximity assay mixture with 488 nm light and candidate compound identification by deconvolution and/or mass-spectrometry; claim 31 introduces 509 nm detection, whereas the current remarks urge support therefor may be found in the original specification at paragraphs 0373-0376 & 0378.
In reviewing the passages proffered, the examiner only finds narrower description of deconvoluting molecular glues that induce proximity between E3 ubiquitin ligase protein and target proteins optionally by mass spectrometry, rather than the broader any two proteins presently claimed. Similarly, concerning 488 nm excitation and 509 nm emission (detection), the passages only describe the even narrower GFP ternary complex formed from DCAF15 E3 ubiquitin ligase glued to RBM39 target with indisulam, as opposed to likewise the considerably broader any two proteins and any candidate compound as now claimed.
Accordingly, the specification as originally filed provided no implicit or explicit support for the new genera now presented in the claims and the remarks do not point to broader description elsewhere of such new material.
Applicants are reminded that it is their burden to show where the specification supports any amendments to the disclosure. See MPEP 714.02, paragraph 5, last sentence and also MPEP 2163.06 I.
MPEP 2163.06 notes “If new matter is added to the claims, the examiner should reject the claims under 35 U.S.C. 112, first paragraph - written description requirement. In re Rasmussen, 650 F.2d 1212, 211 USPQ 323 (CCPA 1981).” MPEP 2163.02 teaches that “Whenever the issue arises, the fundamental factual inquiry is whether a claim defines an invention that is clearly conveyed to those skilled in the art at the time the application was filed...If a claim is amended to include subject matter, limitations, or terminology not present in the application as filed, involving a departure from, addition to, or deletion from the disclosure of the application as filed, the examiner should conclude that the claimed subject matter is not described in that application. MPEP 2163.06 further notes “When an amendment is filed in reply to an objection or rejection based on 35 U.S.C. 112, first paragraph, a study of the entire application is often necessary to determine whether or not “new matter” is involved. Applicant should therefore specifically point out the support for any amendments made to the disclosure.
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 CHRISTOPHER M GROSS whose telephone number is (571)272-4446. The examiner can normally be reached M-F 10-6.
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, Heather Calamita can be reached on (571)272-2876. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/CHRISTOPHER M GROSS/Primary Examiner, Art Unit 1684