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 .
Status of the Application
Claims 1-2, 4-11, 13-19, and 21 are pending and under examination
Claims 3, 12, and 20 are canceled.
The following Office Action is in response to Applicant's communication dated 06/23/2026.
Applicant’s arguments with respect to claim(s) 1-2, 4-11, 13-19, and 21 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument. Specifically, Applicant amended independent claim 1 to further require the combine of moieties to have function/activity of a complete protein. This limitation was not in the previous claim set (Filed 12/12/2023). Hence narrowed the scope of claim 1 and required Examiner to conduct new prior art search directed to newly claimed subject matter.
RE: Applicant argues that Examiner improperly treated the recited "test molecules" and "candidate molecule" as the same population.
In response: The argument is acknowledged to the extent that the candidate molecule is not the entire “plurality of test molecules” collectively. The prior interpretation did clarify that “Examiner interprets the "test molecules" recited in step (1) as corresponding to the molecules being screened in the method, and the "candidate molecule" recited in step (2) as a molecule selected from that plurality based on its ability to form the complex with first and second targets”. Though the final sentence might cause confusion, Examiner is not interpreting the recited "test molecules" and "candidate molecule" as synonyms, rather Examiner is interpreting the "candidate molecule" as a member with ability to form complex chosen from the “plurality of test molecules”.
New Claim Rejections - 35 USC § 102- Necessitated by Amendment
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 2, 4, 8, 10, 11, and 15 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Zheng et al. (US20210382054A1, EFD: October 17th 2018)
Regarding claim 1, Zheng discloses method for screening for a candidate molecule capable of forming a complex with a first target molecule and a second target molecule, the method comprising steps (1) and (2) below:
(1) mixing the first target molecule linked to a first moiety, the second target molecule linked to a second moiety, and a library containing a plurality of test molecules, wherein the first moiety and the second moiety constitute a part or all of a protein; and wherein the first moiety and the second moiety have the structure, function or activity of the undivided protein when they are in proximity or association; [Fig 10 sees below for all components labeled]
(2) recovering, after step (1), a complex containing the first target molecule linked to the first moiety, the second target molecule linked to the second moiety, and the candidate molecule by an a pull-down method using a third molecule capable of detecting that the first moiety and the second moiety are in proximity or association, association, wherein the third molecule is a molecule that reacts with the first moiety and/or the second moiety when the first moiety and the second moiety are in proximity or association. (e.g. post optical detection, affinity pull down may be utilized for further validation of hit compounds [¶0072])
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Regarding claim 2, Zheng discloses identifying the candidate molecule contained in the recovered complex (step (3)). (e.g. After rounds of determining whether the candidate agonist is effective to result in binding the ubiquitin ligase to the neo-substrate, the goal is to identify the candidate agonist as a ubiquitin ligase agonist [Abstract].)
Regarding claims 4, Zheng discloses the third molecule is a molecule that does not substantially react with the first moiety and/or the second moiety when the first moiety and the second moiety are neither in proximity nor in association. (e.g. only compound-induced weak interactions between KEAP1 and KRAS can promote the interactions between two halves of luciferase individually fused to one of the binding proteins. Allow fully functional luciferase to convert luciferin into oxyluciferin through an oxidation and release energy as visible ligh [¶0023 and Fig. 10 shown above]).
Regarding claims 8, Zheng discloses the method is performed in vitro. [¶0032].
Regarding claims 10, Zheng discloses the library has a diversity of 1×104 or more. (e.g. 17,774 compounds were screened [¶0066]).
Regarding claims 11, Zheng discloses the protein is luciferase [Fig. 10].
Regarding claims 15, Zheng discloses The method according to claim 1, wherein the protein providing the first moiety and the second moiety contains an amino acid sequence SEQ ID No. 78 Luciferase/Nanoluc [¶0082-0084]
New Claim Rejections - 35 USC § 103- Necessitated by Amendment
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.
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.
Zheng et al.
Claim(s) 7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zheng et al. (US20210382054A1, EFD: October 17th 2018)
Regarding claims 7, Although Zheng does not expressly disclose repeating the claimed steps, the reference expressly mentioned measuring binding activity using multiple assays [¶0030], hence Zheng recognizes the desirability of carrying out successive screening operations to confirm and enrich candidate agonists. Accordingly, as of the application’ s effective filing date, it would have been prima facie obvious to a person of ordinary skill in the art to repeat the mixing and recovery steps to progressively enrich strong candidates and reduce background from non-specific library members.
Zheng et al. and Faver et al.
Claim(s) 5, 6, 9, 13, 16-19, and 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zheng et al. (US20210382054A1, EFD: October 17th 2018) in view of Faver et al. (ACS Comb. Sci. 11 February 2019; 21 (2): 75–82).
Regarding claims 5 and 13, Zheng does not explicitly disclose eluting the candidate molecule between selection steps from a complex by heat.
Faver discloses contacting a DNA-encoded chemical library with protein target immobilized on beads, washing away unbound library members, and eluting the bound DNA-encoded candidates by heating the beads at 80 °C for 10 min. The resulting eluent in which target protein binding molecules were enriched and further subjected to another round of selection [Experimental Procedures and Abstract].
As of the application’ s effective filing date, it would have been prima facie obvious to a person of ordinary skill in the art to employ the Faver’s DNA-encoded library, including additional candidate recovery step in Zheng’s method because Faver teaches DNA barcodes permit numerous candidates to be pooled and screened simultaneously while maintaining the ability to identify each selected candidate through isolating/enriching the bound candidates for multiple cycle of selections. The modification would predictably increase screening throughput, reduce number of individual assays required, conserve reagents, and enable efficient identification if active compounds.
Regarding claims 9 and 17, Zheng does not disclose the library is a display library or a DNA encoding library.
Faver discloses contacting a DNA-encoded chemical library with protein target immobilized on beads, washing away unbound library members, and eluting the bound DNA-encoded candidates by heating the beads at 80 °C for 10 min. The resulting eluent in which target protein binding molecules were enriched and further subjected to another round of selection [Experimental Procedures and Abstract].
The rationale for combining the Zheng and Faver references with respect to claims 9 and 17 is the same as set forth above for claim 5 and is incorporated herein by reference, as claim 9 and 17 does not introduce a limitation that would alter the motivation to combine or the predictable resulted achieved by the combination.
Regarding claims 6, Faver discloses determining a sequence of a polynucleotide encoding the candidate molecule (e.g. Identifying candidate compounds from these libraries involves affinity selection, DNA sequencing, and measuring enrichment in a sample pool of DNA barcodes. Sequencing step is after enrichment and recovery of selected candidates [Experimental Procedures and Abstract].)
Regarding claims 16, Although Zheng does not expressly disclose repeating the claimed steps, the reference expressly mentioned measuring binding activity using multiple assays [¶0030], hence Zheng recognizes the desirability of carrying out successive screening operations to confirm and enrich candidate agonists. Accordingly, as of the application’ s effective filing date, it would have been prima facie obvious to a person of ordinary skill in the art to repeat the mixing and recovery steps to progressively enrich strong candidates and reduce background from non-specific library members.
Regarding claims 18, Zheng discloses the library has a diversity of 1×104 or more. (e.g. 17,774 compounds were screened [¶0066]).
Regarding claims 19, Zheng discloses the protein is luciferase [Fig. 10].
Regarding claims 21, Zheng discloses The method according to claim 1, wherein the protein providing the first moiety and the second moiety contains an amino acid sequence SEQ ID No. 78 Luciferase/Nanoluc [¶0082-0084]
Zheng et al., Faver et al., and Chen et al.
Claim(s) 14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zheng et al. (US20210382054A1, EFD: October 17th 2018) in view of Faver et al. (ACS Comb. Sci. 11 February 2019; 21 (2): 75–82) and Chen et al. (Adv Drug Deliv Rev. 2013 October 15; 65(10): 1357–1369).
Regarding claim 14, Zheng does not disclose the eluting step is performed by cleaving a first linker located between the first moiety of the protein and the first target molecule and a second linker located between the second moiety of the protein and the second target molecule.
Chen discloses linkers are conventionally used to join functional protein domains in recombinant fusion proteins and cleavable linkers allow the joined functional domains to be released by enzymatic or proteolytic cleavage. [page 7]
As of the application’ s effective filing date, it would have been prima facie obvious to a person of ordinary skill in the art to provide each linker connecting target protein and its associated reporter moiety in Zheng with a cleavable linker because the modification would allow the reporter moiety to be selectively removed after their detection function to reduce steric hindrance between functional domains, decreased activity of target molecules, and altered biodistribution and metabolism of the protein moieties due to the interference between domains [page 6].
Conclusion
No claims are 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 Khai Quynh Tien Pham whose telephone number is (571)272-6998. The examiner can normally be reached M-T, 9-4 ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Heather Calamita can be reached at (571) 272-2876. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KHAI QUYNH TIEN PHAM/ Examiner, Art Unit 1684
/JEREMY C FLINDERS/ Primary Examiner, Art Unit 1684
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