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 .
Priority
Acknowledgement is made that the instant application is a National Stage of International application No. PCT/US2021/038767 (filed 06/23/2021), which claims the benefits of US Provisional Application No. 63/043,430 (filed 06/24/2020).
Claim interpretation
Claim 1 recites an intended use of reducing or inhibiting the function of FANCM in a target cell comprising an impaired, defective or deregulated DNA repair pathway. The intended use does not alter the structure or composition of the claimed composition. Thus, claim 1 is interpreted as any composition comprising a FANCM blocking agent.
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, 67, 70, 79, 81-85, 101-106, and 108-109 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1, 67, 70, and 81 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Independent claims 1, 67, 70, and 81 require the limitation of a FANCM blocking agent wherein… the blocking agent reduces or inhibits a function of FANCM. The issue at present is the scope of “a FANCM blocking agent” covered by the claim. In giving the term “a FANCM blocking agent” its broadest reasonable interpretation, one can include any type of molecule that can reduce or inhibit the function of FANCM including a blocking peptide, an siRNA, a small molecule, an antibody, a nuclease, an a FANCM protein with reduced function (See, e.g. Picket et al, who teaches siRNA, lentiviral vectors expressing FANCM mutants, and small molecule inhibitors of the MM2-RMI interaction with FANCM-BTR, See pg. 94, ln 25 – pg. 95 ln, 4 and pg. 115 lns 25-27).
Additionally, dependent claims 79, 82-85, 101-106, and 108-109 do not further limit the scope of “a FANCM blocking agent” to define a specific type of molecule and thus inherit the deficiencies of the claims from which they depend.
To satisfy the written description aspect of 35 U.S.C. 112(a) for a claimed genus of molecules, it must be clear that: (1) the identifying characteristic of the claimed molecules have been disclosed, e.g., structure or other physical and/or chemical properties, by functional characteristics coupled with known or disclosed correlation between function and structure, by a combination of such identifying characteristics; or (2) a representative number of species within the genus must be disclosed. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
While Applicants’ claims cover the full genus of a FANCM inhibitor, Applicants’ disclosure of such compounds is limited to a CRISPR-Cas9 system and a shRNA.
Regarding disclosure of structural and functional characteristics, the Applicants’ disclose a FANCM blocking agent as being able to reduce or inhibit the function of FANCM. However, no structural or chemical properties are disclosed which must be maintained in order to perform the disclosed function (i.e. the function is not linked to a structure). Therefore, Applicants have not disclosed the identifying characteristics of the claimed molecules.
Regarding disclosure of a representative number of species within the genus, a review of the specification shows that Applicants have disclosed an RNA guided nuclease (CRISPR-Cas9) and a single stranded nucleotide (shRNA). Disclosure two species does not constitute a representative number for such a broad genus as is encompassed by the breadth of “a FANCM blocking agent”. At the time the invention was filed, a limited number of species were taught in the art, including siRNA (See Picket et al, See Zhang et al, See Stoepker et al), lentiviral vectors expressing FANCM mutants, and PIP-199, a small molecule inhibitor of the MM2-RMI interaction within FANCM-BTR (See, e.g. Picket et al, pg. 94, ln 25 – pg. 95 ln, 4 and pg. 115 lns 25-27). However, ultimately the number of species taught by the specification and known from the prior art are not representative of the breadth of the current claims nor sufficient in number to support description and to show possession of the entire genus.
Thus, one of ordinary skill in the art, in looking to the instant specification, would not be able to determine that Applicants were in possession of the invention, as claimed, at the time the invention was made. Accordingly, claims 1, 67, 70, 79, 81-85, 101-106, and 108-109 are considered to lack sufficient written description and are properly rejected under 35 U.S.C. 112, first paragraph.
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)(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.
Claims 1, 67, 70, 81-84, 101, and 104 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Picket et al (WO202024330A2).
Picket et al teaches a methods of inhibiting FANCM activity in order to inhibit the growth and proliferation, and induce death of ALT tumor cells (See abstract). ALT cells are characterized by elevated levels of DNA damage resulting from persistent replication fork stalling (See pg. 2, ln32 – pg. 3, ln 12). Picket et al disclose that inhibiting FANCM in ALT cells results G2/M arrest and cell death (See pg. 33 lns27-30). Picket et al teaches embodiments in which FANCM is inhibited with siRNA, lentiviral vectors expressing FANCM mutants, or PIP-199, a small molecule inhibitor of the MM2-RMI interaction within FANCM-BTR (See pg. 94, ln 25 – pg. 95 ln, 4 and pg. 115 lns 25-27). Picket inhibits FANCM in ALT cell lines including U20S and non-ALT cell lines including Hela cells. FANCM-depleted U20S cells were quickly eliminated from the population, while HeLa cells continued to grow although at lower rates (See pg. 129 lns25-28). Picket et al further teaches a method of treating cancer, by administering a pharmaceutical composition comprising a FANCM antagonist to the individual (See pg. 10 lns 8-10 and claims 2 and 30-31). The antagonist can be a small molecule, antibody, aptamer, suppressor nucleic acid, siRNA, shRNA, or a targeted nuclease (See claims 3-15). The cancer treatment method of Picket et al can further comprise simultaneous, sequential, or separate administration of a chemotherapeutic agent such as carboplatin (See claim 60 and pg. 83, lns 20-29).
Regarding claim 1: Picket et al teaches a composition comprising a FANCM antagonist, specifically siRNA, lentiviral vectors expressing FANCM mutants, and PIP-199, each of which reads on a composition comprising a FANCM blocking agent.
Regarding claims 67, 70, 81, and 101: Picket et al teaches a method of inducing cell death and G2/M arrest (reads on cell cycle arrest) in ALT cancer cells (reads on proliferating cells and cells comprising a deregulated DNA repair pathway) by treating the cells with a FANCM antagonist which reads on contacting the cells with a FANCM blocking agent that reduces or inhibits a function of FANCM. Additionally, Picket teaches administering the FANCM antagonist to an individual with and ALT cancer (reads on cancer cells comprising deregulated homologous recombination repair pathway) as a treatment method.
Regarding claims 82, 83, and 84: Following the discussion of claim 81 above, the cancer treatment method of Picket et al can further comprise treatment with a chemotherapeutic agent such as carboplatin which reads on a second therapy, a chemotherapy, and a platinum-based therapy.
Regarding claims 104: Following the discussion of claim 81 above, Picket et al teaches a method of treating an ALT cancer which reads on the cancer cells are ALT+ cells.
Claims 1, 67, 70, 81, 101, and 104 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhang et al (WO2017146947A1).
Zhang et al teaches a method of inhibiting replication of ALT cells by contacting the cells with an inhibitor of FANCM and an inhibitor of BRCA1 or BLM (See claim 1). Zhang et al teaches co-depletion of FANCM and one of BLM or BRCA1 dramatically increases micronuclei formation and increases synthetic lethality (See ¶0012). Specifically, Zhang et al teaches using siRNA which targets FANCM (See ¶0019). The method of Zhang et al can be used to reduce the number of defective ALT cells such as cancer cells in a subject (See ¶0013, ¶0059, and claim 2).
Regarding claim 1: Zhang et al teaches administering a composition comprising an inhibitor of FANCM, specifically siRNA which targets FANCM. The composition comprising an inhibitor of FANCM reads on a composition comprising a FANCM blocking agent.
Regarding claims 67, 70, 81, and 101: Zhang et al teaches a method of inhibiting replication (reads on inducing cell cycle arrest in a proliferating cell) of ALT cancer cells (reads on cancer cells comprising deregulated homologous recombination repair pathway) by contacting the cells with an inhibitor of FANCM which reads on contacting the cells with a FANCM blocking agent that reduces or inhibits a function of FANCM. Additionally, Zhang et al teaches the method can be used to reduce the number of ALT cancer cells (reads on inducing cell death) in a subject which reads on a method of treating cancer comprising administering an effective amount of a FANCM inhibitor.
Regarding claims 104: Following the discussion of claim 81 above, Zhang et al teaches reducing the number of ALT cancer cells which reads on cancer cells that are ALT+.
Claim 1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Stoepker et al (DNA Repair, 2015).
Stoepker et al studies how FANCM affects PARP inhibitor sensitivity (See abstract). Stoepker et al uses siRNA to inhibit different components of the FANCM DNA repair pathway in cell lines, including siRNA targeting FANCM (See pg. 55, Sec. 2.8). Stoepker et al further teaches patient derived lymphoblasts with FANCM mutations which result in FANCM deficiency are hypersensitive to PARP inhibitors and correcting these mutations in vitro results in PARP inhibitor resistance (See pg. 57, Se. 3.2, and table 1)
Regarding claim 1: Stoepker et al teaches an siRNA which targets FANCM which reads on a composition comprising a FANCM blocking agent.
Stoepker et al further teaches EUFA867-L, a patient derived lymphoblast cell line comprising a c.2171C >A mutation in FANCM which results in FANCM deficiency. The genetic mutation in EUFA867-L cells further reads on a FANCM blocking agent. Therefore, the cell culture of Stoepker et al reads on a composition comprising a FANCM blocking agent.
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.
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.
Claims 1, 67, 70, 79, 81-85, 101, and 104-106 are rejected under 35 U.S.C. 103 as being unpatentable over Picket et al (WO202024330A2).
The teachings of Picket et al are set forth above.
Picket et al anticipates claims 1, 67, 70, 81-84, 101, and 104.
Regarding claim 105: Following the discussion of claim 81 above. Picket et al teaches a method of treating an ALT cancer with a FANCM antagonist. Picket et al further teaches inhibiting FANCM in non-ALT cell lines reduces the growth rate of the cells.
Picket et al does not teach treating a cancer without ALT+ cells.
Although Picket et al does not teach treating a cancer without ALT+ cells, Picket teaches treating non-ALT cancer lines with a FANCM inhibitor reduces their growth rate. Therefore, it would have been prima facie obvious to modify the method of Picket et al to further include treating subjects with non-ALT cancers. One would have been motivated to modify the method of Picket et al because Picket et al teaches FANCM inhibition reduces the growth rate of non-ALT cell lines. There is a reasonable expectation of success because Picket et al teaches FANCM inhibition reduces growth in non-ALT cancer cells.
Claims 1, 67, 70, 81, 101-104, 108, and 109 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al (WO2017146947A1).
The teachings of Zhang et al are set forth above.
Zhang et al anticipates claims 1, 67, 70, 81, 101, and 104.
Regarding claims 102, 103, 108, and 109: Following the discussion of claims 81 and 101 above, Zhang et al teaches reducing the number of ALT cancer cells in a subject by administering a FANCM inhibitor. Zhang et al further teaches co-depletion of FANCM and BRCA1 increases cell lethality.
Zhang et al does not teach treating a subject with cancer cells comprising a variant BRCA1 protein or BRCA1-/- breast or ovarian cancer.
Although Zhang et al does not disclose treating a subject with BRCA1-/- breast or ovarian cancer, Zhang et al teaches inhibiting FANCM and BRCA1 increased cell lethality. Therefore, it would have been prima facie obvious to modify the method of Zhang et al to include treating individuals with BRCA1-/- breast or ovarian cancer. One would have been motivated to treat individuals with BRCA1-/- cancers with the method of Zhang et al because BRCA1-/- cancers have decreased BRCA1 expressed and Zhang et al teaches decreasing both FANCM and BRCA1 expression improves ALT cell lethality. Therefore, inhibiting FANCM in an individual with decreased BRCA expression would be expected to result in improved cancer treatment. There is a reasonable expectation of success because Zhang et al teaches reducing expression of both FANCM and BRCA1 results in increased lethality.
Claims 1, 67, 70, 79, 81-85, 101, and 104-106 are rejected under 35 U.S.C. 103 as being unpatentable over Picket et al (WO202024330A2) in view of Stoepker et al (DNA Repair, 2015).
The teachings of Picket et al and Stoepker et al are set forth above.
Picket et al anticipates claims 1, 67, 70, 81-84, 101, and 104 and renders claim 105 obvious.
Regarding claims 79, 85, and 106: Following the discussion of claims 70 and 81 above, Picket et al teaches a method of inducing cell cycle arrest and cell death in ALT cancer cells (reads on proliferating cells) which can be used as a cancer treatment.
Picket et al does not teach the cancer cells are resistant to a PARP inhibitor as a monotherapy.
Stoepker et al teaches mutations resulting in FANCM deficiency in lymphoblastoid cell lines (reads on cancer cells) increases sensitivity to PARP inhibitors.
Given that Picket et al teaches a method of treating cancer cells with a FANCM inhibitor and Stoepker et al teaches FANCM deficiency increases sensitivity to PARP inhibitors, it would have been prima facie obvious to modify the method of Picket et al to further include treating individuals who are resistant to PARP inhibitor treatment. One would have been motivated to treat individuals resistant to PARP inhibitors with the method of Picket et al because Stoepker et al teaches FANCM deficiency improves sensitivity to PARP inhibitors. Therefore, including a treatment with a FANCM inhibitor could increase PARP sensitivity in individuals who are resistant to PARP inhibitor therapies. There is a reasonable expectation of success because Picket et al teaches the treatment method can be used in combination with chemotherapeutic agents.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARISOL A O'NEILL whose telephone number is (571)272-2490. The examiner can normally be reached Monday - Friday 7:30 - 5:00 EST.
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, Christopher Babic can be reached at (571) 272-8507. 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.
/MARISOL ANN O'NEILL/Examiner, Art Unit 1633
/ALLISON M FOX/Primary Examiner, Art Unit 1633