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 .
Claim Status Summary
Claims 1- 19 are pending.
Claims 1- 19 are considered on the merits.
No Claims are allowed.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 9, 10, and 11, (and dependent claims 12-14, and 19) are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Those claims included in the statement of rejection but not otherwise discussed (claims 2-4, 6-8, 12-16, and 19) are rejected for depending from a rejected claim but failing to remedy the indefiniteness therein.
Regarding claim 9, the phrase "particularly" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claims 10 and 11, the claims begin with the recitations “A method for assigning…” and “The method according to claim 10…” respectively, however they both fail to include any active steps. Therefore they are interpreted as “use” claims. “Attempts to claim a process without setting forth any steps involved in the process generally raises an issue of indefiniteness” (see MPEP 2173.05(q)). Because these claims have no active steps, it is unclear what is the method or process.
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.
Claim 1 (and dependent claims 2-5, 9, 15, and 16) 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention. The specification does not reasonably provide enablement for “A pharmaceutical nucleic acid agent capable of downregulating or inhibiting the activity of the minor spliceosome (MiS) for use in treatment or prevention of recurrence of cancer.”
Breadth of the Claims and Nature of the Invention
Claims 1 is directed toward a therapeutic nucleic acid capable of treating cancer. The nucleic acid of claim 1 inhibits the minor splice some (MiS), thereby inhibiting cancer.
State of the Prior Art and Level of One of Ordinary Skill and Predictability in the Art
Verma (Verma et al. Semin Cell Dev Biol. 2018 Jul;79:103-112.) gives a high level overview of the MiS and disease, “The direct targets for human diseases specific for the minor spliceosome are the unique snRNA and protein components. This includes several components of the U11/U12 intron recognition complex and the U4atac and U6atac snRNAs in the minor tri-snRNP.” Verma further states MiS is only recently being studied for its role in cancer, “Finally, we mention the emerging role for the minor spliceosome in cancer and autoimmune disorders as well as neurodegenerative diseases.” Verma also shows the limited number of MiS associated cancer biomarkers, “In addition to being a target for disease-causing mutations, several components of the minor spliceosome have been reported as cancer biomarkers. Of these, the U11/U12-65K autoantibodies appear to show a reliable association with an increased risk of cancer occurring within 2 years of the onset of scleroderma. Similar associations have been described for U11 snRNA in familial prostate cancers and U11-59K protein in Acute Myeloid Leukemia.” Younis (Younis et al. Elife. 2013 Jul 30;2:e00780.) further explains MiS component snRNA U6atac is involved in tumor suppression pathways “Furthermore, p38MAPK-dependent U6atac modulation can control minor intron-containing tumor suppressor PTEN expression and cytokine production.” (Abstract).
This examiner did not find any art relating the activity of the MiS directly to cancer recurrence and the instant specification highlights this citing “Currently, little is known about MiS in cancer progression” [page 1, line 10]. Androgen deprivation therapy (ADT) is used to treat advanced PCa [specification, page 1, line 12]. “While the role of canonical splicing in cancer has been studied extensively, the present understanding of the interplay between minor intron splicing and cancer is lacking.” [page 1 lines 33- 35].
Direction Provided by the Inventor and Working Examples and Experimentation Required
The specification provides numerous working examples with prostate cancer cells and models. The applicant includes clustering data in Figure 1D of other cancers but this data does not support treatment of cancer via the nucleic acid agent. Figure 6D shows siU6atac knockdown data in prostate, colorectal, kidney endothelial, breast cancer, leukemia, and glioblastoma cell lines. There are numerous other examples with the aforementioned cell lines. While this data exemplifies the nucleic acid agent inhibits snRNA U6atac in cells, it does not enable the broad claim “treatment or prevention of recurrence of cancer.” A reasonable cancer treatment analysis could best be concluded from a clinical trial. However clinical trials are unpredictable. Therefore, it would require a PHOSITA an enormous amount of undue experimentation to take the teachings of the instant specification and use the invention as claimed.
Claims 10 (and dependent claims 12-14, and 19) 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention. The specification does not reasonably provide enablement for “A method for assigning a likelihood of having or developing cancer to a patient, wherein a high likelihood of having or developing cancer is assigned if an expression level of snRNA U6atac is 2 or 3.”
Similarly, Claim 11 and 15 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification does not reasonably provide enablement for “a high likelihood of having or developing a cancer of advanced, therapy resistant phenotype is assigned if an expression level of snRNA U6atac is 2 or 3.” The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Similarly, Claim 17 (and dependent claim 18) are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification does not reasonably provide enablement for “identifying a patient with high risk of recurrence of cancer if said expression level of snRNA U6atac is 2 or 3.” The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Breadth of the Claims and Nature of the Invention
Claims 10, 11, 15, 17 are directed toward methods of measuring snRNA U6atac levels and subsequently translating that level into a score indicating the likelihood of developing cancer or advanced cancer. Claim 17 goes slightly further by including more detailed steps and ending with drug treatment.
State of the Prior Art and Level of One of Ordinary Skill and Predictability in the Art
Regarding cancer, the dysregulation of minor intron splicing has been linked to the Peutz-Jegher's syndrome and myelodysplastic syndrome which frequently proceed to gastrointestinal cancer and acute myeloid leukemia, respectively [specification page 2, lines 5-7]. As recently as 2024, Kumar AM states “Serum PSA testing, DRE, and systematic transrectal ultrasonography-guided biopsies are the core components for the management of prostate cancer” (page 5). To assist the prediction of aggressive cancer upon biopsy or repeated biopsy, several fluid-based molecular biomarkers have been developed, including the PHI, Progensa, 4Kscore, MyProstateScore, Select mdx, ExoDX Prostate, Apifiny, and Proclarix (Kumar AM. page 5). The [4Kscore] analysis of RNA expression of 31 cell cycle progression (CCP) genes normalized to 15 housekeeping genes yields the CCP score (Kumar AM. page 5). However, as cited in the instant specification, “Currently, little is known about MiS in cancer progression” [specification page 1, line 10].
Direction Provided by the Inventor and Working Examples and Experimentation Required
Figures 1J, 2A, and 7A descriptions each discloses “U6atac score of the TMA analysis. ” However, each graph label reads “log10 (U6ATAC sore +1).” Figure 8 has a similar discrepancy. Figure 3A and other figures further disclose “fold change” of U6atac expression levels but these values are in the 2-4 to 24 range, not 0- 3. While many of these graphs indicates U6atac values in the range of 0, 1, 2, 3, none of these figures nor their descriptions indicate these are “expression levels.” Furthermore, there are no further instructions in the specifications to this regard. Finally, there are no instructions in the specification how to convert any of these data values to the “expression level of snRNA U6atac” according to the claims. Therefore, the specification does not show evidence that the applicant was in possession of the claimed invention.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 10, 11, and 12 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. The claim 10 recite(s) “assigning a likelihood of having or developing cancer to a patient.” These judicial exceptions are a mental process. Claim 10 further recites “a high likelihood of having or developing cancer is assigned if an expression level of snRNA U6atac is 2 or 3.” The claim 11 recites “a high likelihood of having or developing a cancer of advanced, therapy resistant phenotype is assigned if an expression level of snRNA U6atac is 2 or 3.” These judicial exceptions are laws of nature. The claim 12 recites “wherein said cancer is selected from glioblastoma, breast cancer, chronic myeloid leukemia (CML), bladder cancer, colon cancer, kidney cancer and prostate cancer.” These are natural phenomenon. These are judicial exceptions because they may be performed in the human mind and the other is a correlation between a naturally occurring chemical and its naturally occurring effects. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claim does not recite any additional elements.
Claim Rejections - 35 USC § 102
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)(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- 8 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Kanadia (Kanadia US 20230293525 A1, effectively filed 2020 July 30).
Claim interpretation
The clause “for use in treatment or prevention of recurrence of cancer” is interpreted as intended use language. The claim as written is not a process claim, but rather a product. Therefore, the intended use language does not provide any additional structural limitations and therefore is not given any patentable weight.
Kanadia teaches “included herein are pharmaceutical compositions comprising a minor spliceosome inhibitor” [0030]; and “In an aspect, anti-sense oligonucleotides, morpholinos, and siRNAs that bind the U12, U4atac and U6atac snRNAs can be used to inhibit the minor spliceosome” [0024].
Regarding claim 2, Kanadia teaches all of the elements of claim 1.
Furthermore, the nature of an siRNA is such that it binds its target (U6atac snRNAs in this instant) and inherently downregulates or inhibits its expression.
Regarding claim 3, Kanadia teaches all of the elements of claim 1.
Furthermore, an siRNA inherently is or encodes an antisense oligonucleotide.
Regarding claim 4, Kanadia teaches all of the elements of claim 1.
Furthermore, an siRNA is an siRNA.
Regarding claim 5 and 6, 7, 8, Kanadia teaches all of the elements of claim 1.
Furthermore, because "treatment of advanced therapy resistant cancer" is an intended use, the prior art does not need to specifically disclose an agent being used as "treatment of advanced therapy resistant cancer." Rather, the prior art need only discloses an agent that has the capability of treating advanced cancer. The instant specification defines "advanced therapy resistant cancer" as having high expression of U6atac snRNAs, “The inventors have observed a strong difference, regarding U6atac expression, between 1) benign tissue and cancer 2) primary and advanced or metastatic cancer. Their conclusion is that the relationship is valid for any cancer, wherein a higher U6atac score signals a more advanced stage of cancer”[page 7, lines 13- 15; page 2, lines 28- 34]. The agent of Kanadia targets U6atac snRNAs, and therefore is capable of treating "advanced, therapy resistant cancer.”
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) 9, 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kanadia (Kanadia US 20230293525 A1, effectively filed 2020 July 30) as applied to claim 1 above, and further in view of Okunade (Okunade et al. J Obstet Gynaecol. 2020 Jul;40(5):602-608.), and Khodarev (Khodarev US 20170268001 A1).
Regarding claim 9, Kanadia teaches all of the elements of claim 1.
Kanadia does not teach “wherein said agent is administered in combination with a platinum-containing complex, particularly in combination with a platinum-containing drug selected from carboplatin, satraplatin, cisplatin, dicycloplatin, nedaplatin, oxaliplatin, picoplatin, and/or triplatin.”
Kanadia further teaches their composition is directed toward “a method inhibiting replication of an RNA/DNA virus” [Abstract].
Okunade teaches “About 99.7% of cervical cancer cases are caused by persistent genital high-risk human papillomavirus (HPV) infection” (Abstract).
Khodarev teaches “the present invention relates to a composition for treating cancer in a subject in need thereof, and the composition comprises a therapeutically effective amount of at least one rbRNA ( e.g., snRNA) or its functionally equivalent fragment, and a pharmaceutically acceptable carrier,” [0012]; and “snRNA may often be divided into two classes” [0183]; and “the second class, … consists of … U6atac.” [0184]; and “the composition further comprises another therapeutic agent” [0024]; and “the other therapeutic agent is selected from the group consisting of … cis-platinum preparations or platinum derivatives, such as Cisplatin” [0025]; and “the agent includes at least one of a shRNA, a siRNA, a micro-RNA mimic, an antisense oligonucleotide,”[0048].
It would have been obvious for a person having ordinary skill in the art (PHOSITA) at the time of filing to have combined the pharmaceutical nucleic acid agent of Kanadia with the platinum-containing complex of Khodarev, based on the teaching of Okunade because it is simply combining prior art elements according to known methods to yield predictable results. As described above, both Kanadia and Khodarev taught pharmaceutical compositions directed toward the snRNA U6atac. Kanadia’s composition was directed toward viruses and Khodarev’s composition was directed toward cancer. Okunade taught viruses cause cancer. Both Kanadia’s virus inhibitor and Khodarev’s platinum-containing adjuvant were effective. Therefore, a PHOSITA in the field of endeavor of treating viral based cancers would necessarily look toward the combination of Kanadia’s viral inhibitor and Khodarev’s platinum-containing adjuvant and would have predicted a successful combination.
Regarding claim 16, Kanadia, Okunade, and Khodarev teach all of the elements of claim 1 and its application toward the treatment of cancer for claim 9.
Kanadia further teaches “methods and compositions for the treatment of viral infections” [Title] and Khodarev further teaches “Treatment of a cancer in a subject in need thereof is provided herein, as are compositions, kits, and methods for treating cancer” [0156].
Conclusion
This examiner was unable to find prior art that reads on claim 10, 11, 15, and 17.
Regarding claim 12, the claim limitation has similar language to claim 6 and would therefore be rejected for similar reasons as claim 6. However, claim 12 depends from claim 10 and as noted above, is currently free of the prior art and therefore claim 12 is currently immune to a prior art rejection.
Similarly, claim 13 has similar claim limitation language to claim 7 and similarly depends from claim 10 and therefore follows the analysis above.
Similarly, claim 19 has similar claim limitation language to claim 1 and similarly depends from claim 17 and therefore follows the analysis above.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AARON DUREL WARD whose telephone number is (571)272-8495. The examiner can normally be reached Monday to Thursday 8:00AM 6:00PM.
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, Neil Hammell can be reached at 15712705919. 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.
/AARON DUREL WARD/Examiner, Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636
Prosecution Insights