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 .
Election/Restrictions
Applicant elects Group 2; Species 1 (claim 1) applicant elects innate resistance; Species 2 (claims 4,5,16, and 20) applicant elects Non-small cell lung cancer (NSCLC); Species 3 (claims 13, 15, and 16) applicant elects FGF; Species 4 (claims 16 and 20) applicant elects EGFR, in the reply filed on March 06, 2026 is acknowledged.
Claims 1, 14 and 17-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claims.
Election was made without traverse in the reply filed on March 06, 2026.
Claim Objections
Claim 16, is objected to because of the following informality, applicant uses the acronym NSCLC without spelling out the proper term first.
Appropriate correction is required.
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 2-13,15, and 16 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.
Claim 2 recites in section (ii) the limitation, culturing tissues with “an additional agent that is a single agent, to thereby select an agent that does not have anti-cancer effect as a single agent”. It is unclear if the claim is requiring the presence of an agent having the anti-cancer effect, or if the claim is discovering an agent that has the anti-cancer effect. The claim requires the both the presence of an anti-cancer agent as a single agent in (i), and selecting an agent (ii), wherein (ii) refers by antecedent to “said EVOC” introduced in (i). It is unclear how the agent can be present, and also selected. Further, if the additional agent does not indicate traits that would fall within the category of “anti-cancer effect” what are the steps of the method—is there a progression in the assessment assay or does the assessment end? As such, it is unclear if ‘2ii’ should be delineated into additional steps or if a step in the process is missing. Due to the uncertainty in the scope of the claim, the claim is indefinite.
Claims 13 and 15 each recite references to tables: claim 13 recites “selected from the group of targets listed in Table 3” and claim 15 recites “selected from the group of combinations listed in Table 4A”. The claims rely on said tables to define the scope of the claimed invention; however, incorporation by reference to a specific table is permitted only in exceptional circumstances where there is no practical way to define the invention in words. The scope of the claim is unclear since it is not known which aspects of the table constitute claim limitations. Accordingly, the claims fail to particularly point out and distinctly claim the subject matter regarded as the invention. Appropriate correction is required. See MPEP 2173.05(s).
Claims 3-13,15, and 16 inherit and fail to cure the deficiencies of the claims discussed above.
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 2-13, 15, and 16 rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (abstract idea) without significantly more. The claim(s) recite(s) a method of selecting and determining an agent(s) used as cancer treatment.
With regards to Step 1, claim 2 is considered to be in a statutory category of process.
With regards to Step 2A, prong 1, claim 2 is directed towards the abstract idea of evaluating a change of cell viability detected in an EVOC system, with and without an agent and/or agents and making a correlation. This falls into the mental process grouping of abstract ideas as it involves collecting data, analyzing, and making a determination (selecting). These steps can be performed in the human mind using routine observation and reasoning, and thus constitute a mental process.
With regards to Step 2A, prong 2, regarding claim 2, the additional elements (recited in 2i, 2ii, and 2iii) are for routine and conventional methods of assessing agents with cancer cells for cytotoxicity as evidenced in the prior art ( Kim et al.). The mental steps of selecting treatment or determining therapeutic efficacy of a combination of agents are not integrated into a practical application because the steps of culturing cancer tissue (2i, 2ii, and 2iii), and determining combinations that are efficacious(2iv), are data gathering, mental processes, and interpretation of correlation and/or making data assessments based on measurements regarding agent toxicity—all of which can be done mathematically and/or are mental steps of selecting. Step 2b, is a highly general step regarding selecting and determining agents, relative to their response in the EVOC system; regarding administration of treatment, the step is void when the agent(s) do not indicate an outcome that is efficacious compared with current treatment regimens provided to patient. Accordingly, the claim as a whole, does not recite additional elements that amount to significantly more than the judicial exception itself and does not integrate the exception into a practical application.
With regards to Step 2B: in claim 2, the additional elements beyond the abstract idea (mental processes), selecting and determining cytotoxic agents in an EVOC system, culturing tissue(s), detecting cytotoxic activity of agents, relative to innate resistance and/or sensitivity, are recited in a generic manner and are routine conventional in the prior art, as evidenced by Kim et al. As such, the claims do not recite additional elements that alone or together amount to significantly more than the judicial exception itself.
Claim 3, similarly recites assessment of responsiveness to treatment, without further integration of the judicial exception.
Claims 4 and 5, further recites, at a high level of generality—select cancer cohorts, without further integration of the judicial exception.
Claims 6-13, 15, and 16 further recites at a high level of generality additional active steps of modification and/or selection of agent(s), these additional steps are routine and conventional to the art as evidenced by Kim et al. Summarily, the claim limitations generically claim the agents and/or assessment in an EVOC system for additional data gathering and analysis steps. The claims are directed to a method of use, however, they do not integrate into a practical application since they do not use the result of comparison for any purpose. The additional elements such as, a target that is a receptor and a protein and/or secreted protein, re-assessing resistance/sensitivity relative to generally recognized agents, and/or targets, are conventional as evidenced by Kim et al and/or Krell et al. Accordingly, the claims do not recite additional elements that alone or together amount to significantly more than the judicial exception.
For the forgoing reasons, claims 2-13,15, and 16 are not deemed to encompass patent eligible subject matter under 35 USC § 101.
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.
Claims 2-13,15, and 16are rejected under 35 U.S.C. 103 as being unpatentable over Krell, J. et al., Prediction of Drug Response Using an Ex Vivo Organ Culture (EVOC) on Fresh Human Tumour Samples From Metastatic Patients (CURESPONSE) (ClinicalTrials.gov ID: NCT04599608; Last Posted Date 2020-10-22) and further in view of Kim et al., Patient-derived lung cancer organoids as in vitro cancer models for therapeutic screening. Nature Communications. 2019; 10:3991; pp.1-15.
Regarding Claims 2, 3,6, and 9 Krell, J et al., (Researcher View; Outcome Measures) teaches a method of treating cancer in a subject in need:
Regarding step 2 (a)(i): culturing a cancerous tissue, in an ex vivo organ culture (EVOC) and determining the efficacy of agents that are anti-cancer, as a single agent.
Regarding step 2 (a)(ii): further culturing the cancerous tissues with an additional agent(s).
Regarding step 2(a)(iii): assessment continues, as described in 2(a)(ii) along with treatment and assessment to other therapeutic agents.
Regarding step 2(a) (iv): the results of the clinical study inform whether EVOC prospectively determines clinical treatment benefits, for a certain clinical treatment, and a given patient.
Regarding step 2 (b) and claim 3: assess treatment responsiveness from sensitivity and specificity analysis of at least 70% in predicting patient clinical response from patient cohorts treated with a specific anti-cancer therapy, along with evaluation and characterization of viable (i.e. sensitive) and resistance in the EVOC following treatment and assessment response to other therapeutic agents based on tumor heterogeneity.
Regarding claims 6 and 9: further including tumor heterogeneity from tumor gene profiling and genomic profiling of tumors compared with germline data (which provide mutation profiles, associated with responsiveness to an anti-cancer agent), and/or in vitro fluorescent-activated cell sorting (FACS) analysis from biopsy samples, of previously diagnosed patients, receiving treatment, with metastatic disease. .
Krell et al., do not specify in their teaching, the following:
Regarding claim 2(ii): an agent that does not have an anti-cancer effect as a single agent, however it inhibits expression and/or activity of a target conferring innate resistance or increases activity of a target conferring innate sensitivity to said anti-cancer agent.
Krell et al., does teach patients with metastatic cancers but does not specify non-small cell lung cancer (claims 4 and 5), a targeted therapy agent (claim 7), cytotoxic agent (claim 8), a target that is a secreted factor or protein that is expressed by cancer cells (claims 10 and 11), or an additional agent that binds a target and/or receptor that is FGF, or a mutated egfr (claims 12 ,13 15, and 16 (elected embodiments iii and iv)).
However, regarding claims 2 (ii), 4, 5, 7, 8, 10-12, Kim et al., teaches targeted agent, erlotinib, a tyrosine kinase inhibitor (TKI) to treat NSCLC with innate resistance (wherein, EGFR is a protein receptor) (page 11, Figure 6), and the agent is cytotoxic; as examined in an EVOC drug screen model for lung cancer organoids (LCO), (page 7, ‘LCOs for in vitro patient-specific drug trials’).
Regarding claims 13,15, and 16 (iii and iv), Kim et al., teaches fibroblast growth factor (FGF2, bFGF, FGF10, FGF4 among others) to establish five subtypes of lung cancer organoids (page 2, ‘Results’) which activates intrinsic/innate resistance pathways to erlotinib and/or treatment of EGFR mutated NSCLC with MET amplification, with a tyrosine kinase inhibitor that is a MET inhibitor, crizotinib (as a additional agent), along with erlotinib (page 7, ‘”LCOs for in vitro patient-specific drug trials” and page 9-10, paragraph 1 -continued).
Therefore, it would have been obvious for one of ordinary skill in the art at the effective date of filing to have combined the methods of Krell et al., regarding EVOC testing for patient treatment, to examine for EGFR mutated NSCLC as taught by Kim et al., and further assess innate resistance to targeted TKI therapy, erlotinib, following incubation of biopsied NSCLC tissue(s) with FGF-family secondary agents; sequentially evidencing treatment with TKI, crizotinib as an additional agent to overcome innate resistance – consequently resulting in concomitant treatment analysis and patient-specific therapeutics. Secondly, it would have been obvious to a skilled artisan to combine said methods of Krell et al., and Kim et al., to perform combinatorial analyses of genomic/genetic variants along with targeted therapy analyses from patient-derived tissues with the use of an ex vivo model to further personalize, patient treatment.
Accordingly, the motivation to combine the methods of Krell et al., with Kim et al., are simply to provide a cancer specific EVOC model to assess and predict therapeutic outcome for patients, relative to genetic mutations present in said cancer(s) along with cancer-associated metabolic and/or cellular pathways activated and/or repressed by innate resistance and/or sensitive mutations, that then determine primary/secondary therapeutic decision-making and/or prognostics. The prior art independently and/or combined teach EVOC methods along with therapy decision-making, and further teaches NSCLC with mutated EGFR, along with targeted therapies that bind to EGFR, that are cytotoxic agents, and treatment affected by FGF-family expression resulting in a second therapeutic agent, for the combined result-effective and patient-specific treatment. Therefore, it is prima facie obvious that the combined art is able to produce the same outcome prescribed by the instant application.
Conclusion
No claims are deemed allowable.
Correspondence Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ENUSHA KARUNASENA whose telephone number is (571)272-3972. The examiner can normally be reached Monday-Friday 7:30am-5pm.
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/ENUSHA KARUNASENA/Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
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