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 .
Drawings
The drawings are objected to for the following reasons:
37 CFR 1.84 (u)(1) states “View numbers must be preceded by the abbreviation "FIG."”
In the current case, the view numbers for Figures 1-23 are preceded by the word "Figure" instead of the abbreviation "FIG.".
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 60, 79 and 90 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 60 recites “further comprising … administration of a chemotherapeutic agent, or, wherein the method does not comprise … administration of a chemotherapeutic agent”. As recited, the “or” allows for either administration of a chemotherapeutic agent or no administration of a chemotherapeutic agent, which covers all possible scenarios. Claims 30 and 50, from which Claim 51 depends, recite a method “comprising” and therefore, allow for both an additional step of administrating a chemotherapeutic agent or no additional step of an additional chemotherapeutic agent. Therefore, Claim 60 fails to further limit Claim 51.
Claims 79 and 90 recites additional limitation for an inhibitor. However, Claims 76 and 77 respectively do not integrate the inhibitor into any step such that the methods of Claim 76 and Claim 77 would be further limited. Therefore, Claim 79 and 90 fail to limit Claims 76 and 77 respectively.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claims 76, 77, 79 and 90 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
Step 1: Process, Machine, Manufacture or Composition of matter
Regarding Claim 76, Claim 76 recites, “A method of identifying whether a subject suffering from cancer is suitable for treatment”. Therefore, Claim 76 is a process.
Regarding Claim 77, Claim 77 recites, “A method of determining whether a subject is responding to treatment”. Therefore, Claim 77 is a process.
Step 2A, Prong One: Law of Nature, A Natural Phenomenon, or an Abstract Idea
MPEP 2106.4(a)(2).III recites, “The courts consider a mental process (thinking) that "can be performed in the human mind, or by a human using a pen and paper" to be an abstract idea.” As an example, MPEP 2106.4(a)(2).III.A recites, “Examples of claims that recite mental processes include: … claims to "comparing BRCA sequences and determining the existence of alterations," where the claims cover any way of comparing BRCA sequences such that the comparison steps can practically be performed in the human mind, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 763, 113 USPQ2d 1241, 1246 (Fed. Cir. 2014)”
Regarding Claim 76, Claim 76 recites a method comprising the step of “determining whether the cancer is ALT cancer”.
Regarding Claim 77, Claim 77 recites a method comprising “determining the presence and/or extent of genomic instability at one more or more telomeres in a cell taken from a subject” and/or “determining the presence and/or level of ALT activity in a cell in a cell taken from a subject”.
Claims 76 and 77 recite the steps “determining” and are therefore mental processes.
Step 2A, Prong Two: Additional Elements That Integrate the Judicial Exception Into a Practical Application
MPEP 2106.04(d)(2) recites, “A claim reciting a judicial exception is not directed to the judicial exception if it also recites additional element(s) demonstrating that the claim as a whole integrates the exception into a practical application. One way to demonstrate such integration is when the additional elements apply or use the recited judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition.
MPEP 2106.04(d)(2).c further recites, “The treatment or prophylaxis limitation must impose meaningful limits on the judicial exception, and cannot be extra-solution activity or a field-of-use … For example, consider a claim that recites (a) administering rabies and feline leukemia vaccines to a first group of domestic cats in accordance with different vaccination schedules, and (b) analyzing information about the vaccination schedules and whether the cats later developed chronic immune-mediated disorders to determine a lowest-risk vaccination schedule. Step (b) falls within the mental process grouping of abstract ideas enumerated in MPEP § 2106.04(a). While step (a) administers vaccines to the cats, this administration is performed in order to gather data for the mental analysis step, and is a necessary precursor for all uses of the recited exception. It is thus extra-solution activity, and does not integrate the judicial exception into a practical application.”
Regarding Claim 76, Claim 76 does not recite a step of treatment but instead recites “the subject is identified as suitable for treatment”. This step is also a mental process.
Regarding Claim 77, Claim 77 does not recite a step of treatment but instead recites in the preamble “determining whether a subject is responding to treatment”. As recited in MPEP2106.04(d)(2).c, the administration is performed in order to gather data for the mental analysis step and does not integrate the judicial exception into a practical application.
Step 2B: Claim Amounts to Significantly More
MPEP 2106.05 recites, “The second part of the Alice/Mayo test is often referred to as a search for an inventive concept. … an "inventive concept" is furnished by an element or combination of elements that is recited in the claim in addition to (beyond) the judicial exception, and is sufficient to ensure that the claim as a whole amounts to significantly more than the judicial exception itself. Alice Corp., 573 U.S. at 27-18, 110 USPQ2d at 1981 (citing Mayo, 566 U.S. at 72-73, 101 USPQ2d at 1966).”
Regarding Claim 76, Claim 76 does not provide any additional steps for an inventive concept.
Regarding Claim 77, Claim 77 does not provide any additional steps for an inventive concept.
Conclusion
Claims 76 and 77 recite mental processes that do not integrate the judicial exception into a practical application or claim significantly more than the mental processes. Therefore, Claim 76 and 77 are rejected under 35 USC 101 for claiming an abstract idea.
Regarding dependent Claims 79 and 90, Claims 79 and 90 recite limitations for the inhibitor, but Claims 76 and 77 respectively do not recite a step integrating the inhibitor. Therefore, Claim 79 and 90 fail to overcome the rejections of Claim 76 and 77 and are rejected under 35 USC 101 for claiming an abstract idea.
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.
Claims 1, 2, 7, 16, 17, 19, 22, 30, 31, 36, 45, 50, 51, 53, and 60 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhang, D., WO 2017/146947, published August 31, 2017.
Regarding Claim 1, Zhang teaches a method inhibiting ALT cell viability comprising reducing FANCM expression in the ALT cell: “a method for alleviating a condition characterized by
dysfunctional cells, where the dysfunction itself is characterized by cells using the alternative
lengthening of telomers, or "ALT", as the way to maintain their telomeres. More specifically, it
relates to inhibiting replication stress response or destruction of, said cells by inhibiting
expression of FANCM, and one or both of BRCA1 and BLM,” (p. 1, [001]). Therefore, Claim 1 is anticipated by Zhang.
Regarding Claim 2, Zhang teaches a method wherein the FANCM expression is reduced by administering a FANCM antagonist to the individual: “The cells were depleted of FANCM using siRNA” (p. 4, [0019]). Therefore, Claim 2 is anticipated by Zhang.
Regarding Claim 7, the instant specification provides siRNA as an example of a suppressor nucleic acid: “Suppressor nucleic acids, such as siRNAs” (p. 55, line 13). Zhang teaches a method with a siRNA, which is a suppressor nucleic acid. Therefore, Claim 3 is anticipated by Zhang.
Regarding Claim 16, Zhang teaches a method where one of BRCA1 or BLM is inhibited and therefore, either BRCA1 or BLM is not inhibited, which reads on “wherein activity or expression of BLM or BRCA1 is not reduced in the ALT cell”. Therefore, Claim 16 is anticipated by Zhang.
Regarding Claim 17, Zhang teaches a method in U2-OS cells, which are human bone osteosarcoma epithelial cells or epithelial cancer cells (p. 3, [0018]). Therefore, Claim 17 is anticipated by Zhang.
Regarding Claim 19, Zhang teaches a method inhibiting expression of FANCM and therefore, is a method of inhibiting FANCM ATPase activity because less FANCM is available. Therefore, Claim 19 is anticipated by Zhang.
Regarding Claim 22, the instant specification teaches a siRNA is a genetic inhibitor: “For
example, the genetic inhibitor may be siRNA” (p. 10, lines 25-26). Zhang teaches a genetic inhibitor, a small molecule inhibitor, or a peptide inhibitor of FANCM: “The inhibition can be at the nucleotide level using … siRNA … small molecules … antibodies, antibody fragments” (p. 10, [0058]). Therefore, Claim 22 is anticipated by Zhang.
Regarding Claim 30, Zhang teaches a method of inhibiting FANCM expression in am ALT cell as described in Claim 1. Zhang further teaches their invention may be used to treat cancer: “The methodology may be used in combination with other methodologies for inhibiting and/or eliminating dysfunctional cells. For example, several types of cancer cells are characterized by ALT. By inhibiting the mechanism which alleviates the ALT, standard drug therapies can be modified to … reduce the strain on normal cells caused by severe therapies” (p. 10-11, [0059]). Therefore, Claim 30 is anticipated by Zhang.
Regarding Claim 31, the instant specification provides as an example of a FANCM antagonist as a siRNA: “A FANCM antagonist … may reduce or suppress the expression of FANCM, for example a suppressor nucleic acid” (p. 44, lines 27-28); “Suppressor nucleic acids, such as siRNAs” (p. 55, line 13). Zhang teaches a method using a siRNA to reduce the expression of FANCM: ““The cells were depleted of FANCM using siRNA” (p. 4, [0019])”. Therefore, Claim 31 is anticipated by Zhang.
Regarding Claim 35, Zhang teaches siRNA reduces the expression of FANCM. Therefore, Claim 35 is anticipated by Zhang.
Regarding Claim 36, Zhang teaches a method using a siRNA, which is a suppressor nucleic acid. Therefore, Claim 36 is anticipated by Zhang.
Regarding Claim 45, Zhang teaches a method where one of BRCA1 or BLM is inhibited and therefore, either BRCA1 or BLM is not inhibited, which reads on “wherein activity or expression of BLM or BRCA1 is not reduced in the ALT cell”. Therefore, Claim 16 is anticipated by Zhang.
Regarding Claim 50, Zhang teaches a method inhibiting expression of FANCM and therefore, is a method of inhibiting FANCM ATPase activity because less FANCM is available. Therefore, Claim 50 is anticipated by Zhang.
Regarding Claim 51, Zhang teaches a method comprising administering an inhibitor of ATPase activity of FANCM, a siRNA. Therefore, Claim 51 is anticipated by Zhang.
Regarding Claim 53, the instant specification teaches a siRNA is a genetic inhibitor: “For
example, the genetic inhibitor may be siRNA” (p. 10, lines 25-26). Zhang teaches a genetic inhibitor, a small molecule inhibitor, or a peptide inhibitor of FANCM: “The inhibition can be at the nucleotide level using … siRNA … small molecules … antibodies, antibody fragments” (p. 10, [0058]). Therefore, Claim 53 is anticipated by Zhang.
Regarding Claim 60, Claim 60 is rejected under 112d as an improper dependent claim. For compact prosecution, Claim 60 is interpreted as the treatment further comprises administration of another chemotherapeutic agent. Zhang teaches a method further comprising further treatment with a chemotherapeutic agent: “The methodology may be used in combination with other methodologies for inhibiting and/or eliminating dysfunctional cells. For example, several types of cancer cells are characterized by ALT. By inhibiting the mechanism which alleviates the ALT, standard drug therapies can be modified to … reduce the strain on normal cells caused by severe therapies” (p. 10-11, [0059]). Therefore, Claim 60 is anticipated by Zhang.
Claims 76, 77, 79 and 90 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hakin-Smith, et. al., The Lancet, Vol. 361, p. 836-838, published March 8, 2003.
Regarding Claim 76, Claim 76 is interpreted as having the sole step of determining whether the cancer is ALT cancer as claimed the determination of ALT cancer is the only step necessary to identify a subject as suitable for treatment with an inhibitor of the FANCM-RMI interaction. Hakin-Smith teaches a method of identifying whether a subject suffering from cancer has ALT cancer: “We obtained tissue samples from 77 patients … We measured the length of telomeres for all tumour samples using standard methods … we assigned these tumours an ALT phenotype” (p. 837). Therefore, Claim 76 is anticipated by Hakin-Smith.
Regarding Claim 77, the preamble of Claim 77 does not provide an additional limitation because the recited steps do not recite the inhibitor of FANCM-RMI interaction. Hakin-Smith teaches a method comprising determining the presence and/or extent of genomic instability at one or more telomeres in a cell taken from a subject as described in Claim 76. Therefore, Claim 77 is anticipated by Hakin-Smith.
Regarding Claim 79, Claim 79 recites a limitation for the inhibitor of the FANCM-RMI interaction, but Claim 76 does not recite a step using the FANCM-RMI interaction. Hakin-Smith teaches the steps of Claim 76. Therefore, Claim 79 is anticipated by Hakin-Smith.
Regarding Claim 90, Claim 90 recites a limitation for the inhibitor of FANCM-RMI interaction, but Claim 77 does not recite a step using the FANCM-RMI interaction. Hakin-Smith teaches the steps of Claim 77. Therefore, Claim 90 is anticipated by Hakin-Smith.
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.
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.
Claims 19 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang, D., WO 2017/146947, published August 31, 2017 as applied to Claim 1 above, and further in view of Voter, A., et. al., Journal of Biomolecular Screening, Vol. 21, No. 6, p. 626-633, published July, 2016.
Regarding Claim 19, Zhang anticipates Claim 1.
Zhang does not teach a method comprising of disrupting the FANCM-RMI interaction.
Voter teaches a method comprising of disrupting the FANCM-RMI interaction using PIP-199: “a 34–amino acid motif within FANCM called MM2” (p. 627, col. 1); “identification of a single compound that specifically disrupted the RMI core complex–MM2 interaction” (p. 627, col. 1); “PIP-199, the most selective inhibitor discovered in the screen” (p. 628, col. 1). Voter provides motivation for using their method: “Such inhibitors … could serve as lead compounds in developing new strategies for treating chemoresistant tumors” (p. 633).
Regarding Claim 19, it would have been obvious to one skilled in the art to perform a simple substitution with the method of Zhang with PIP-199 of Voter to create the method of Claim 1 using Voter because both methods teach a method of targeting FANCM. One skilled in the art would have high expectation of success because Voter provides dose-response curves (p. 631, Figure 4) and SPR results (Figure 5, p. 632) for PIP-199. Voter provides motivation to use PIP-199 for use with chemoresistant tumors. Therefore, Claim 19 is obvious over Zhang in further view of Voter.
Regarding Claim 22, Zhang does not teach a small molecule disrupting the FANCM-RMI interaction. Voter teaches a small molecule, PIP-199. Therefore, Claim 22 is obvious over Zhang in further view of Voter as described for Claim 19.
Claim 46 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang, D., WO 2017/146947, published August 31, 2017 as applied to Claim 1 above, and further in view of Muntoni, A. and Reddel, R., Human Molecular Genetics, Vol. 14, No. 2, published October 15, 2005.
Regarding Claim 46, Zhang anticipates Claim 30.
Zhang does not teach the ALT cancer is a mesenchymal or epithelial cancer.
Muntoni teaches ALT cancers are mesenchymal or epithelial: “ALT is most commonly activated in tumors of neuroepithelial origin (astrocytomas) or mesenchymal origin” (p. R194, col. 1).
It would have obvious for one skilled in the art to apply the method of Zhang to ALT cancers which are mesenchymal or epithelial cancers because Muntoni teaches the most common ALT cancers are mesenchymal or epithelial cancers. One skilled in the art would have a reasonable expectation of success because Zhang tested their method in U2-OS cells, which are human bone osteosarcoma epithelial cells or epithelial cancer cells (p. 3, [0018]). Therefore, Claim 46 is obvious over Zhang in further view of Muntoni.
Claim 87, is rejected under 35 U.S.C. 103 as being unpatentable over Tsai, W. and Chang W., Gene Function Analysis, NY, Humana Press, p. 321-338, published 2014 and Murshedi, F., Role of FANCM in Telomere Maintenance in Alternative Lengthening of Telomeres (ALT) Human Cells, Masters Thesis, University of Toronto, 2010.
Regarding Claim 87, Tsai teaches a method of screening for a compound that reduces the expression of a gene through siRNA: “the protocols described in this chapter … provides the basis for an improved approach to screen and identify the most potent siRNA for therapeutic purposes” (p. 323, para 3).
Tsai does not teach compounds that induce the death of ALT cancer cells or FANCM.
Murshedi teaches siRNA knockdown of FANCM results in the death of ALT cancer cells: “siRNA knockdown of FANCM results in poor growth and increased cell death in ALT” (p. 52, 2.3.3.1).
It would have been obvious to one skilled in the art before the effective filing date to used the teachings of Tsai to screen for a siRNA with the teachings of Murshedi to screen for an siRNA that results in the death of ALT cancer cells because Tsai teaches their method identifies the most potent siRNA for therapeutic purposes. One skilled in the art would have a reasonable expectation of success because Murshedi used an siRNA to cause cell death in ALT cancer cells. Therefore, Claim 87 is obvious over Tsai and Murshedi.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Krishna Nuggehalli Ravindra whose telephone number is (571)272-2758. The examiner can normally be reached M-Th, alternate F, 8a-5p est.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammell can be reached at (571) 270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/K.N.R./Examiner, Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636