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 .
Claims and Previous Objections/Rejections Status
Claims 353,355-371,373-376 and 378-388 are pending in the application. Claims 358-361 and 379-383 are withdrawn from consideration.
Any objections and/or rejections from previous office actions that have not been reiterated in this office action are obviated.
Response to Arguments
Applicant's arguments filed 7/13/26 have been fully considered but they are not persuasive.
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.
Claim(s) 353,355,362-367,369-371,376 and 384-387 is/are rejected under 35 U.S.C. 103 as being
unpatentable over Napoli et al. (The EMBO Journal (2009) 28, 1708-1719) in view of Sanders et al. (Biochim. Biophys. Acta 1743 (2005) 141-150) and Mijatovic et al. (Mol Cancer Ther (2008) 7 (5): 1285-1296) and in further view of Vlach et al. (The EMBO Journal vol. 15 no. 23 pp. 6595-6604, 1996), Sears (Cell Cycle 3:9, 1133-1137; September 2004) and Kumar et al. (Cancer Informatics 2017, 16, 1-7) as stated in the office action mailed 3/13/26.
Applicant asserts that Napoli is completely silent about “imaging the cell for the condensate”. Although c-myc promoter-targeted siRNAs blocked assembly of the transcription pre-initiation complex in PC3 cells, such assessment was by ChIP, rather than by imaging the cells. Napoli never assessed the “formation, dissolution, size or composition” of condensates by imaging.
The reference of Napoli was not explicitly used to teach of a condensate but was used to teach of contacting a cell comprising c-Myc with siRNA test agent and of the investigation of the mechanism by which siRNA acts on c-Myc. Napoli teaches of imaging siRNAs in prostate cancer cells with an inverted microscope equipped with a digital camera. Therefore, Napoli does disclose imaging c-Myc within cells.
The reference of Sanders et al. was used to teach that c-Myc is largely localized to the nucleolus and is present in nucleolar extracts (e.g. condensate).
The reference of Mijatovic et al. was used to teach that c-MYC is sequestered in nucleoli of tumor cells.
The c-Myc of Napoli et al. encompasses the component of a condensate of the instant claims as c-Myc is largely localized to the nucleolus (e.g. condensate) and is sequestered in the nucleoli of tumor cells.
Therefore, the c-Myc of Napoli is present in condensates of tumor cells and it would have been predictable to image the c-Myc within condensates of tumor cells with the inverted microscope equipped with a digital camera.
Napoli et al. teaches that c-myc promoter-targeted siRNA interfered with transcription initiation blocking the assembly of the pre-initiation complex that encompasses the modification of one or
more properties of the condensate, such as formation or composition of the instant claims. The microscopy examination of the siRNA-treated cells is used to reveal the morphological changes.
Therefore, It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to image the morphological changes of the c-Myc condensate in the siRNA-treated cells of Napoli et al. to investigate the mechanism by which siRNA modifies of one or more properties of the condensate, such as formation or composition.
Applicant asserts that Sanders et al. is completely silent about “contacting a cell comprising the condensate or a component thereof with the test agent,” much less assessing if the test agent modulates one or more condensate properties (formation, dissolution, size or composition) or using such modulation as a read out of the test agent’s ability in modulating transcriptional activity associated with a condensate.
The reference of Sanders et al. was not used to teach of contacting a cell comprising the condensate or a component thereof with the test agent but was used to teach that c-Myc is largely localized to the nucleolus and is present in nucleolar extracts (e.g. condensate).
The reference of Napoli was used to teach of the investigation of the mechanism by which siRNA acts on c-Myc and imaging siRNAs in prostate cancer cells as they interfere with transcription initiation blocking the assembly of the pre-initiation complex as well as that stated above.
The Myc of Napoli et al. encompasses the component of a condensate of the instant claims as c-Myc is largely localized to the nucleolus (e.g. condensate) and is sequestered in the nucleoli
of tumor cells.
Therefore, the c-Myc of Napoli is present in condensates of tumor cells and the examination of
the siRNAs interference with transcription initiation blocking the assembly of the pre-initiation complex
encompasses that modulation is a read out of the test agent’s ability in modulating transcriptional activity associated with a condensate.
Applicant asserts that Sanders discloses a model proposed where the nucleolus serves to sequester c-Myc for down-regulation via proteasomal degradation and we speculate that the nucleolus may act to sequester c-Myc in quiescent hepatocytes while providing a pool of c-Myc that is readily available to teach its target in the nucleus. Therefore, Sanders merely states that it is a speculation.
The reference of Sanders explicitly states that immunofluorescence and Western blot analysis on adult liver and cultured adult hepatocytes revealed that endogenous and transiently transfected c-Myc was predominantly localized to the nucleolus and is therefore not speculation. The sequestration in the nucleolus may provide for a pool of c-Myc that, upon release, can quickly reach its targets in the nucleus.
Applicant asserts that Mijatovic et al. does not disclose, teach or suggest using a modulation in one or more condensate properties selected from formation, dissolution, size and composition as a read out of a test agent’s ability in modulating transcriptional activity associated with a condensate.
The reference of Mijatovic et al. was not used to teach of modulation in one or more condensate properties selected from formation, dissolution, size and composition as a read out of a test agent’s ability in modulating transcriptional activity associated with a condensate. Mijatovic et al. was used to teach that c-MYC is sequestered in nucleoli/condensates of tumor cells.
The reference of Sanders et al. was used to teach that c-Myc is largely localized to the nucleolus and is present in nucleolar extracts (e.g. condensate).
The reference of Napoli was used to teach of the investigation of the mechanism by which siRNA acts on c-Myc and imaging siRNAs in prostate cancer cells as well as that stated above.
The c-Myc of Napoli et al. encompasses the component of a condensate of the instant claims as
c-Myc is largely localized to the nucleolus (e.g. condensate) and is sequestered in the nucleoli of tumor
cells.
Therefore, the c-Myc of Napoli is present in condensates of tumor cells.
Napoli et al. teaches that c-myc promoter-targeted siRNA interfered with transcription initiation blocking the assembly of the pre-initiation complex that encompasses the modification of one or
more properties of the condensate, such as formation or composition of the instant claims.
Applicant asserts that the unexpected finding that transcription activity associated with a condensate can be regulated by modulating the condensate, such as by affecting its formation, dissolution, size and/or composition. The inventors discovered that a change in one or more of the recited condensate properties can be used as identifiers for test agents that regulate transcription. The present invention thus provides a novel and inventive scheme for screening agents that regulate transcription based on the modulation of condensate properties. Hence, the claimed methods are superior for new drug identification and high-throughput screening, especially considering that aberrant condensates are found to associate with many diseases.
The reference of Napoli teaches of the method of assessing the ability of siRNAs to block c-myc transcription wherein it was determined that promoter-targeted siRNA inhibits transcription of the c-Myc transcription factor by blocking the assembly of the pre-initiation complex that encompasses the modification of one or more properties of the condensate, such as formation or composition of the instant claims.
The reference of Mijatovic et al. was used to teach that c-MYC is sequestered in nucleoli of tumor cells.
The reference of Sanders et al. was used to teach that c-Myc is largely localized to the nucleolus and is present in nucleolar extracts (e.g. condensate).
The Myc of Napoli et al. encompasses the component of a condensate of the instant claims as c-Myc is largely localized to the nucleolus (e.g. condensate) wherein the Myc is sequestered in the nucleoli
of tumor cells.
Therefore, the c-Myc of Napoli is present in condensates of tumor cells.
It would not have been unexpected to modulate the transcription activity associated with a condensate comprising c-Myc upon introduction of siRNAs as Napoli teaches that siRNAs blocks (e.g. modulates) c-myc transcription wherein c-Myc is sequestered in the nucleoli/condensates of tumor cells and.
The arguments of counsel cannot take the place of evidence in the record. Examples of attorney statements are not evidence and must be supported by an appropriate affidavit or declaration include statements regarding unexpected results. MPEP § 716.01 (c).
Applicant asserts that Vlach, Sears and Kumar are completely silent about “imaging the cell for the condensate.”
The references of Vlach, Sears and Kumar were not used to teach of imaging the cell for the condensate.
The reference of Vlach was used to teach that the effect of Myc is mediated by a non-covalent sequestration of p27 and requires transcriptionally active Myc-Max dimers.
The reference of Sears was used to teach that the life cycle of c-Myc involves double phosphorylation followed by dephosphorylation via PP2A of the c-Myc component of the condensate
The references of Kumar was used to teach that c-Myc is an IDP comprising regions called intrinsically disordered regions (IDRs).
Conclusion
Claims 356-357,368,373-375,378 and 388 are objected to as being dependent upon a rejected
base claim, but would be allowable if rewritten in independent form including all of the limitations of
the base claim and any intervening claims.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MELISSA JEAN PERREIRA whose telephone number is (571)272-1354. The examiner can normally be reached M9-3, T9-3, W9-3, Th9-2, F9-2.
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/MELISSA J PERREIRA/Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
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