DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This Office action is in response to the communication filed 12-31-25.
Claims 1, 2, 5, and 10-13 are pending in the instant application.
Claims 10-13 are withdrawn from further consideration as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1, 2 and 5 have been examined on their merits as set forth below.
Response to Arguments and Amendments
Withdrawn Objections/Rejections
Any objections or rejections not repeated in this Office action are hereby withdrawn.
Maintained Rejections
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph 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 the first paragraph of pre-AIA 35 U.S.C. 112:
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, 2 and 5 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for the in vitro inhibition of TTP expression using siRNA of SEQ ID No. 1 or No. 2 in human lung carcinoma and human colorectal carcinoma cells, A549 and HCT116 respectively, and the measurement of DNA breaks, apoptotic cells, analysis of chromosomal aberrations after replicative stress was applied in vitro, does not reasonably enable methods for enhancing sensitivity of DNA replication inhibitory anticancer-agent-resistant cancer cells in any subject comprising any siRNA, shRNA, miRNA, gRNA, or ASO inhibitor of tristetraprolin for the reasons set forth in the Office action mailed 10-1-25 and as set forth below.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
Applicant’s Arguments
Applicant argues
The Examiner also contends that the claims are not enabled because the specification allegedly fails to teach how to administer TTP inhibitors to a subject. Applicant respectfully submits that this position applies an unduly stringent enablement standard. The specification teaches the identity of the molecular target (TTP), the nature of the inhibition (suppression of TTP expression), the relevant anticancer agents (hydroxyurea and cisplatin), and the resulting enhancement in sensitivity. Once this relationship is disclosed, implementation of the claimed methods using known nucleic acid-based inhibitors falls within the routine skill of the art.
At the time of filing, siRNA, shRNA, miRNA, ASOs, and gRNA-based inhibitors were well-established technologies, and methods for formulating and administering such agents were widely known. The claims do not require any specific delivery vehicle, route of administration, or dosing regimen, nor do they demand optimization beyond routine experimentation. Moreover, the claims are directed to enhancing sensitivity to anticancer agents, not to guaranteeing a therapeutic outcome or cure. The enablement requirement does not obligate the specification to address every conceivable clinical variable or delivery challenge, but only to enable a person of ordinary skill in the art to practice the claimed invention without undue experimentation.
The Office Action places significant emphasis on alleged unpredictability in translating in vitro gene inhibition results to in vivo administration. However, such considerations do not negate enablement where the specification discloses the operative biological mechanism and the claimed implementation relies on conventional techniques. The claims do not recite a novel delivery technology or an unconventional therapeutic framework. Rather, they apply known inhibitory agents to a known molecular target for a purpose that is explicitly demonstrated in the specification. Any routine selection among known administration methods does not rise to the level of undue experimentation. In view of the foregoing, the specification provides adequate written description and enablement for the claimed invention. The amended claims are now tightly aligned with the disclosed embodiments, rely on predictable and well-understood inhibitory modalities, and require no more than routine skill to implement.
Response to Applicant’s Arguments
As stated previously, the following factors have been considered in determining that the specification does not enable the skilled artisan to make and/or use the invention over the broad scope claimed.
The breadth of the claims:
The claims are drawn to methods for enhancing sensitivity of DNA replication inhibitory anticancer-agent-resistant cancer cells comprising administering a composition comprising an anticancer adjuvant comprising a tristetraprolin (TTP) inhibitor optionally comprising any siRNA, shRNA, miRNA, gRNA, or ASO inhibitor of tristetraprolin, or an siRNA represented by SEQ ID NO: 1 or SEQ ID NO: 2, which DNA replication inhibitory anticancer agent optionally comprises 5-fluorouracil or cisplatin, which composition optionally further comprises a DNA replication inhibitory anticancer agent, and which cancer is optionally lung or colorectal cancer.
Teachings in the art and in the specification.
Teachings in the art:
Roberts et al (Nature Rev., Drug Discovery, Vol. 19, pages 673-694 (2020)) teaches on page 673 that “achieving efficient oligonucleotide delivery, particularly to extrahepatic tissues, remains a major translational limitation.”
Kobelt et al (Cancer Gene Therapy in Gene Therapy of Cancer: Methods and Protocols, Methods in Molecular Biology, Vol. 2521, pages 1-15 (Springer Nature 2022)) teach that limitations to cancer gene therapy relate to limitations in gene transfer efficiency (see esp. pages 3-4).
In addition, Osborn et al (Nucleic Acid Therapeutics, Vol. 28, No. 3, pages 128-136 (2018)) state the following about challenges to siRNA delivery on page 128:
…The primary challenge facing the clinical development of small interfering RNAs (siRNA) has been overcoming barriers that impede in vivo delivery. siRNAs are large, polyanionic macromolecules with intrinsically poor pharmacological properties. Unmodified siRNAs have a half-life of less than 5 min in circulation, and they do not permeate intact cellular membranes…
Damase et al (Frontiers in Bioengineering and Biotechnology, Vol. 9, Article 628137, pages 1-24 (2021)) on page 13 also address the challenges of using RNA-based drugs:
Targeted delivery is a major hurdle for effective RNA therapeutics, a hurdle that must be overcome to broaden the application of clinical translation of this type of therapeutic. …There is a need for novel delivery vehicles that will deliver the RNA drug to the site of therapeutic action facilitating the entry of the RNA drug into the cytoplasm where it may exert its effect…
Bost et al (ACS Nano, Vol. 15, pages 13993-14021 (2021)) on page 13993 also address the current challenges of oligonucleotide therapeutics:
…Historically, the largest hindrance to the widespread usage of ON therapeutics has been their inability to effectively internalize into cells and escape from endosomes to reach their molecular targets in the cytosol or nucleus…
Suswam et al (J. Neurooncolo., Vol. 113, pages 195-205 (2013)) teach that tristetraprolin (TTP) may be suppressed in glioma cell growth because of extensive phosphorylation. Suswam teaches the mutagenesis of TTP by converting 8 phosphoserine residues to alanines, which mutant had a significantly enhanced negative effect on growth factor expression in glioma cells at the post transcriptional and transcriptional levels. The mutant protein became stabilized, displaying significantly increased antiproliferative effects compared to wild type TTP. Suswam concludes that glioma cells suppress TTP function through phosphorylation of critical serine residues, contributing to growth factor upregulation and tumor progression (see esp. the text on page 195, Figure 1 on page 197).
Brennan et al (Cancer Res., Vol. 69, No. 12, pages 5168-5176 (2009)) evaluated the expression of some well characterized AU-rich element binding proteins (ARE-BPs), including tristetraprolin (TTP). Restoring TTP expression in an aggressive tumor cell line suppressed three key tumorgenic phenotypes, cell proliferation, resistance to proapoptotic stimuli, and expression of vascular endothelial growth factor mRNA. Brennan reported, however, that cellular consequences of TTP expression varied across different cell models. According to Brennan, gene array data sets illustrated that suppression of TTP expression is a negative prognostic indicator in breast cancer and patients with low tumor TTP mRNA levels were more likely to present increased pathologic tumor grade, vascular endothelial growth factor expression and mortality from recurrent disease (see page 5168). And on page 5175 Brennan concludes that “rigorous identification of TTP substrate mRNA populations across different cell types will be required to delineate the specific post transcriptional regulatory networks controlled by this factor.”
Brooks et al (Biochim. et Biophys. Acta, Vol. 1829, pages 666-670 (2013)) provide a review of TTP, also known as Nup475, G0S24 and TIS11, and is a member of the CCCH tandem zinc finger protein family. This review focuses on TTP interactions with mRNA and proteins, and examining TTP’s mechanism of action in promoting mRNA decay. Brooks also discusses the proposed regulation of TTP by phosphorylation, and evidence for TTP to operate as a translational regulator. Brooks concludes that a great deal of work remains for a complete understanding of the regulation of TTP function and its targets. Brooks concludes that TTP is clearly an mRNA stability regulator, its role in translational regulation requires additional work to establish the precise mechanism of action. Brooks states on page 676:
Finally, establishing the regulation of TTP expression, subcellular localization, and function in normal versus diseased tissues should enable a transition from the laboratory to bedside applications.
Carrick et al (Archives of Biochem. And Biophys., Vol. 462, pages 278-285 (2007)) compare expression of TTP family transcripts in normal human tissues and cancer cell lines. Carrick concludes (see esp. pages 282-283) that several issues must be considered in discussions of the characterization of “TTP equivalents” that were presented in comparing transcript expression. One concern is the target and biochemical specificity of the three human TTP family members. Another is the mechanism of the relative over -expression of some of the family members observed in certain of the tumor cell lines. Also of interest is consideration of major variations in expression levels seen in certain cancer cell types, possibly affecting the expression of mRNAs and proteins involved in the neoplastic process. (Emphases added].
Griseri et al (Human Molecular Genetics, Vol. 20, No. 23, pages 4556-4568 (2011)) discloses synonymous polymorphism of the TTP gene which affects translation efficiency and response to Herceptin treatment in breast cancer patients. Griseri investigated whether TTP correlated with tumor aggressiveness in breast cancer. Immunoblot analysis determined the amount of TTP protein in different breast cancer cell lines and found an inverse correlation between aggressiveness and metastatic potential. Griseri also found that TTP mRNA levels were very variable among cells lines and did not correlate with protein levels. (See entire document) On page 4564 Griseri concludes the following:
…Our work confirms a crucial role for TTP in breast cancer progression but at the same time underlies the complexity of the study of TTP gene expression for basic and translational research.
Deng et al (Tissue and Cell, Vol. 94, 102785, pages 1-8 (2025)) teach that TPP, also known as zinc finger protein 36 homolog (ZFP36), is an AU-rich element binding protein that regulates mRNA stability by recognizing and binding to AU rich elements within 3’ untranslated regions, mediating the degradation of a variety of proliferation related gene mRNA and inhibiting the abnormal proliferation of malignant tumors. TTP shuts down pro inflammatory cytokine gene expression by promoting relative mRNA decay. Deng shows that TPP overexpression suppressed the proliferation and migration capabilities in esophageal squamous cell carcinoma cells in vitro (see entire document, esp. the text on pages 1-2, Fig. 3 on page 4).
Sanduya et al (Frontiers in Bioscience, Vol. 17, pages 174-188 (2012)) provide a review of the structure, function and regulation of TTP, illustrating TTP’s role in ARE-mediated mRNA decay, and TTP’s role in cancer and inflammation (see esp. the text on pages 174-175, Figure 1 on page 175, Figure 2 on page 177).
Ross et al (Ageing Res. Review, Vol. 11, pages 473-484 (2012)) review research with TTP revealing its importance in the balance of inflammatory response mechanisms. TTP knockout mice exhibit severe chronic inflammatory phenotypes. However, TTP expression can also be induced in response to selected pro-inflammatory and anti-inflammatory stimuli, and many TTP substrate transcripts encode factors central to the control of inflammation and other pro-tumorigenic processes. Ross proposed a model for coordinated control of pro-oncogenic post-transcriptional gene regulatory networks by TPP (see esp. the Abstract, text on page 475, Figure 1 on page 476).
[Emphases added][Citations omitted].
Teachings in the specification:
As stated previously, the specification teaches the following:
FIGS. 1A to 1F correspond to Example 1, and FIG. 1A shows the result of the immunoblot analysis with the indicated antibodies after 20 J/m* UV-C treatment of A549 (human lung carcinoma) cells transfected with the siCTRL and siTTP. FIG. 1B shows the result of the immunoblot analysis with the indicated antibodies after 20 J/m UV treatment of A549 cells transfected with the vector expressing siRNA-resistant TTP.
FIG. 1C shows the result of the immunostain of control or UV-treated cells with the indicated antibodies, and the nuclei stained with Hoechst 33342 are depicted as dotted circles.
FIG. 1D is a quantification of the percentage of p-CHKl-positive cells from UV-treated data of FIG. 1c.
FIG. 1E shows cells treated with the indicated inhibitors after UV irradiation, fixed for 2 hours, and then immunostained with an anti-p- CHK1 antibody. In each experiment, >100 cells were randomly chosen to determine the percentage of p-CHK1- positive cells.
FIG. 1F shows the results of immunoblotting by treating either siCTRL- (control, 10 nM control siRNA) or siTTP transfected cells with DMSO or 4 mM HU for 2 hours, and then releasing them for the indicated periods.
FIGS. 2A to 2D correspond to Example 2, and FIG. 2A 10 shows that either siCTRL- or siTTP-transfected A549 (huma lung carcinoma) cells were sequentially pulse-labeled with IdU (red) for 20 min and CldU (green) for 40 min with or without UV-C (20 J/m2) exposure between the labeling procedures and were subjected to DNA fiber analysis. The ratios of CldU to IdU were calculated from active replication forks.
FIG. 2B shows that A549 cells transfected with siCTRL, siTTP or a combination of siTTP and the vector expressing siRNA-resistant TTP, were pulse labeled with IdU, treated with 4 mM HU for 2 4h, and release from HU block in presence of CldU for 6 h. Single-strand DNA (ssDNA; blue) was labelled with ssDNA-specific antibodies. Percentages of stalled forks were calculated by dividing the number of red-only tracts (stalled forks) by the total number of red-only plus red-green tracts (stalled and restarted forks, respectively). Analyses were performed on a minimum of 200 individual DNA fibers.
FIG.2C shows that A549 cells transfected with siCTRL, siTTP or a combination of siTTP and the vector expressing siRNA-resistant TTP were treated with 4 mM HU for 2 h, released for the indicated periods, and were pulse-labeled with EduU for the last 1 h. The recovery of S phase progression is presented as a percentage of EdU positive cells at 6 h after the release from HU treatment. In each experiment, >100 cells were randomly chosen to determine the percentage of EdU-positive cells.
FIG. 2D shows that A549 cells transfected with either siCTRL or siTTP were sequentially pulse-labeled with IdU and CldU, followed by treatment with 4 mM HU for 6 h and then were subjected to DNA fiber analysis. The ratio of CldU to IdU in terms of length was calculated from active replication forks (red-green). The median value of over 200 fibers per experimental condition is indicated as bars. Statistical analysis was conducted using Mann-Whitney test.
FIGS. 3A to 3E correspond to Example 3, and FIG. 3A shows the result of quantitative real-time PCR (qRT-PCR) of the mRNA levels for indicated genes of A549 (human lung carcinoma) cells transfected with either siCTRL or siTTP treated without actinomycin D.
FIG. 3B shows the result of qRT-PCR of the mRNA levels for indicated genes of A549 cells transfected with either the empty vector or the vector expressing SiRNA-resistant TTP treated with actinomycin D for the indicated times.
FIG. 3C shows the result of the RNA immunoprecipitation analysis performed with the antibody against TTP on the lysates of A549 cells transfected with either the empty vector or TTP-expressing vector with or without UV irradiation. The presence of TTP-binding sites in the 3’UTR of Claspin mRNA was analyzed by RT-PCR. GAPDH mRNA served as a negative control.
FIG 3D shows the result of the luciferase reporter assays of A549 cells cotransfected with PSICHECK2 luciferase reporter constructs (encoding mRNA containing either ARELWT or ARE1Mut) and either the TTP-expressing vector or SiTTP. Luciferase reporter activity was measured as the ratio of firefly luciferase signals to Renilla luciferase Signals.
FIG. 3E shows the result of immunoblot analysis with the indicated antibodies of whole-cell lysates of A549 cells which were cotransfected with either siCTRL or SiTTP and either the empty vector or vector expressing SiRNA-resistant TTP. A549 cells were treated with mock or 20 J/m* UV-C.
FIGS. 4A to 4C correspond to Example 3, and FIG. 4A shows the result of the immunoblot analysis with the indicated antibodies after mock or J/m* UV-C treatment of A549 (human lung carcinoma) cells transfected with the indicated siRNAs, or the vector expressing siRNA-resistant Claspin.
FIG. 4B shows the result of DNA fiber analysis of either siTTP- or siClaspin-transfected cells sequentially pulse-labeled with IdU(red) for 20 min and CldU (green) for 40 min with or without UV-C (20 J/m) exposure between the labeling procedures. The length ratio of CIdU to IdU was calculated from the active replication bifurcation (red-green, n>100).
FIG. 4C shows the result of DNA fiber analysis after treatment with 4 mM HU for 6 h of A549 cells transfected with the indicated siRNAs or the vector expressing siRNA-resistant Claspin sequentially pulse labeled with IdU and CldU. The ratio of CldU to IdU in terms of length was calculated from active replication forks (red-green). The median value of over 200 fibers per experimental condition is indicated as bars. Statistical analysis was conducted using Mann-Whitney test.
FIGS. 5A and 5B correspond to Example 4. A549 (human lung carcinoma) cells transfected with the indicated siRNAs were cotransfected with the empty vector or vector expressing siRNA-resistant TTP. The transfected cells were sequentially pulse-labeled with IdU and ClduU, each for 20 min.
FIG. 5A shows the representative images of the replicating tracts from indicated cells.
FIG. 5B shows the median value of over 150 fibers per experimental condition indicated as bars. Statistical analysis was conducted using Mann-Whitney test.
FIGS. 6A to 6E correspond to Example 5, and FIG. 6A shows the result of the immunostaining with the indicated antibodies of either siCTRL- or siTTP-transfected A549 (human lung carcinoma) cells treated with either 4 mM HU or 10 pM cisplatin. In each experiment, >100 cells were randomly chosen to quantify the colocalization of 53BP1 and yH2AX foci.
FIG. 6B show the result of the comet assay. The comet assay uncovered increased numbers of DNA breaks in TTP-deficient cells. Either siCTRL or siTTP-transfected A549 cells were treated with either 4 mM HU or 10 uM cisplatin. After drug removal, the extent of DNA breaks was assessed in a comet assay during alkaline electrophoresis.
FIG. 6C shows the analysis of chromosomal aberrations in HCT116 (human colorectal carcinoma) cells after replication stress was applied. Either siCTRL- or siTTP-transfected cells were treated with either 4 mM HU or 20 pM cisplatin and then incubated with 0.1 pg/ml colcemid. Representative images illustrate Giemsa-stained metaphase spreads and the arrows indicate abnormal chromosomes. In total, 100 metaphases were scored for each experiment.
FIG. 6D shows the result of the detection of apoptotic cells by immunofluorescence staining of cleaved caspase 3, an apoptosis factor. A549 cells were grown on coverslips and transfected with either siCTRL or silTTP After 48 h, the cells were treated with either 4 mM HU or 20 pM cisplatin and allowed to recover for 24 h before fixation, followed by immunostaining of cleaved caspase 3. In each experiment, >100 cells were randomly chosen to determine the percentage of cleaved-caspase-3-positive cells.
FIG. 6E shows the TUNEL assay. The TUNEL assay shows fluorescent labeling of apoptotic (TUNEL, green) versus all nuclei (Hoechst 33342, blue) among A549 cells after replication stress was applied. Either siCTRL- or siTTP-transfected cells were treated with either 4 mM HU15 or 20 uM cisplatin, and the TUNEL assay was performed. In each experiment, >200 cells were randomly chosen to determine the percentage of TUNEL-positive cells.
FIG. 7 shows the result of the RT-PCR of the mRNA levels of the indicated genes of HCT116 (human colorectal carcinoma) or ARPE-19 cells (the normal epithelial cells) co-transfected with either siCTRL or siTTP and either the control vector(empty vector) or vector expressing siRNA- resistant TTP.
FIG. 8 shows the locations of putative AREs in the Claspin mRNA.
FIG. 9 shows the representative cell cycle profiles of siCTRL- or siTTP-transfected A549 (human lung carcinoma) cells. Either siCTRL- or siTTP-transfected cells were labeled with EdU for 2 h and harvested. The cells were stained with Alexa 488 azide to detect EdU incorporation and with propidium 1odide (PIL) to detect DNA. Representative graph shows EdU incorporation on the y-axis and total DNA on the x-axis.
[Emphases added][Citations omitted].
Contrary to Applicant’s assertions, the examples provided in the instant specification, of the in vitro inhibition of TTP in A549 and HCT116 cells, and analyses of TTP expression and other cellular phenotypes as a result of TTP inhibition, are not representative or correlative of the ability to enhance sensitivity of any DNA replication inhibitory anticancer-agent-resistant cancer cell in any subject.
In light of the teachings in the art and the specification, one skilled in the art would not accept on its face the examples provided in the instant disclosure as being correlative or representative of the ability to provide treatment effects in a subject. Since the specification fails to provide the requisite guidance for the treatment in any subject, and since determination of the factors required for accomplishing this in any subject is highly unpredictable, it would require undue experimentation to practice the invention over the broad scope claimed.
For these reasons, the instant rejection for lacking enablement over the full scope claimed is properly maintained.
Claims 1, 2 and 5 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 for the reasons of record set forth in the Office action mailed 10-1-25 and as set forth below.
Applicant’s Arguments
Applicant argues:
The specification clearly demonstrates possession of the claimed invention. As described in the specification, inhibition of TTP expression results in increased DNA damage, chromosomal aberrations, and apoptosis when cells are exposed to DNA replication-inhibitory anticancer agents such as hydroxyurea and cisplatin. These effects are directly demonstrated in the experimental examples, thereby establishing the fundamental biological relationship that forms the basis of the claims.
The amended claims are now expressly limited to enhancing sensitivity to hydroxyurea or cisplatin, both of which are specifically disclosed and experimentally evaluated in the specification. Thus, the claims no longer seek coverage of an undefined or speculative class of anticancer agents, but instead correspond directly to disclosed embodiments.
The Examiner further asserts that the specification does not support the full scope of the recited TTP inhibitors. However, the specification expressly discloses inhibition of TTP expression using siRNA and explains that suppression of TTP expression is the operative mechanism underlying the observed enhancement in sensitivity. A person of ordinary skill in the art would readily understand that other well-known nucleic acid-based inhibitory modalities- including shRNA, miRNA, guide RNA (gRNA), and antisense oligonucleotides (ASOs)-operate through the same predictable, sequence-specific gene-silencing mechanisms.
Accordingly, the claims do not recite a disparate or unpredictable genus, but rather a cohesive group of functionally equivalent inhibitors that achieve the same disclosed biological effect. The written description requirement does not mandate separate experimental exemplification of each such modality where, as here, the specification conveys possession of the common inventive concept and the genus is predictable to those skilled in the art.
Response to Applicant’s Arguments
The claims are drawn to methods for enhancing sensitivity of DNA replication inhibitory anticancer-agent-resistant cancer cells comprising administering a composition comprising an anticancer adjuvant comprising a tristetraprolin (TTP) inhibitor optionally comprising any siRNA, shRNA, miRNA, gRNA, or ASO inhibitor of tristetraprolin, or optionally comprising an siRNA represented by SEQ ID NO: 1 or SEQ ID NO: 2, which DNA replication inhibitory anticancer agent optionally comprises 5-fluorouracil or cisplatin, which composition optionally further comprises a DNA replication inhibitory anticancer agent, and which cancer is optionally lung or colorectal cancer.
As stated previously, the teachings in the specification are not representative of the large genus of modulators claimed.
Teachings in the specification
The teachings in the specification are described above in the scope of enablement rejection. The specification teaches in vitro inhibition of TTP expression using siRNA of SEQ ID No. 1. This single siRNA inhibitor is not representative of the genus comprising any TTP inhibitor, and further whereby TTP expression is inhibited in any subject.
The specification fails to provide the requisite guidance for using the large genus of modulatory agents instantly claimed, and further whereby treatment for anticancer agent resistance is reduced and sensitivity of inhibitors is enhanced in any cell in any subject. Since the disclosure fails to describe the common attributes and characteristics concisely identifying members of the proposed genus of modulators, and because the claimed genus is highly variant, the description provided is insufficient, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the broad genus of modulatory agents instantly claimed.
Thus, Applicant was not in possession of the broadly claimed genus.
Conclusion
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.
Certain papers related to this application may be submitted to Art Unit 1637 by facsimile transmission. The faxing of such papers must conform with the notices published in the Official Gazette, 1156 OG 61 (November 16, 1993) and 1157 OG 94 (December 28, 1993) (see 37 C.F.R. ' 1.6(d)). The official fax telephone number for the Group is 571-273-8300. NOTE: If Applicant does submit a paper by fax, the original signed copy should be retained by applicant or applicant's representative. NO DUPLICATE COPIES SHOULD BE SUBMITTED so as to avoid the processing of duplicate papers in the Office.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jane Zara whose telephone number is (571) 272-0765. The examiner’s office hours are generally Monday-Friday, 10:30am - 7pm. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Jennifer Dunston, can be reached on (571)-272-2916. Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (703) 308-0196.
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Jane Zara
1-26-26
/JANE J ZARA/Primary Examiner, Art Unit 1637