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 .
Claims 1-12 are currently pending and under examination.
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 1-4 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because the claims simply recite a use for resistance to genomic DNA without providing any method steps. As such, the claims do not fall within one of the four categories of patent eligible subject matter.
Claims 5-12 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural correlation/law of nature and an abstract idea without significantly more. This judicial exception is not integrated into a practical application and the claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons set forth below.
35 U.S.C. § 101 requires that to be patent-eligible, an invention (1) must be directed to one of the four statutory categories, and (2) must not be wholly directed to subject matter encompassing a judicially recognized exception. M.P.E.P. § 2106. Regarding judicial exceptions, “[p]henomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.” Gottschalk v. Benson, 409 U.S. 63, 67 (1972); see also M.P.E.P. § 2106. The unpatentability of abstract ideas was confirmed by the U.S. Supreme court in Bilski v. Kappos, 561 U.S. 593, 601 (June 28, 2010) and Alice Corp. Pty. Ltd. v. CLS Bank Int’l, 134 S. Ct. 2347, 2354 (2014). See also Myriad v Ambry, CAFC 2014-1361, -1366, December 17, 2014. The unpatentability of laws of nature was confirmed by the U.S. Supreme Court in Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. 66, 71 (2012). “[L]aws of nature, natural phenomena, and abstract ideas” are not patentable. Dia-mond v. Diehr, 450 U. S. 175, 185 (1981); see also Bilski v. Kappos, 561 U. S. at 601 (2010).
Claims Analysis:
As set forth in MPEP 2106, the claims have been analyzed to determine whether they are directed to one of the four statutory categories (STEP 1).
The instant claims are directed to methods and therefore are directed to one of the four statutory categories of invention. With regard to claim 5 and 6, although they depend from claim 1 which is a ‘use claim” as set forth above, the claims do recite a step of determining.
The claims are then analyzed to determine if they recite a judicial exception (JE) (STEP 2A, prong 1) [Mayo Collaborative Services v. Prometheus Labs., Inc., 132 S. Ct. 1289, 1293 (2012), Alice Corp. Pry. Ltd. v. CLS Bank Int'l, 134 S. Ct. 2347 (2014)].
The claimed invention is directed to determining the resistance of genomic DNA against damage by radiation based on the damage indicated using single cell gel electrophoresis. The claims further provide an intended correlation between the extent of DNA damage (an an additional biomarker-claim 5) and an indication of proliferative disease or susceptibility for proliferative disease, including cancer. However, this recitation is a natural correlation between levels of DNA damage and susceptibility or detection of proliferative diseases, including cancer. With regard to the natural correlation, as in Mayo, the relationship is itself a natural process that exists apart from any human action. The recitation of “determining” “evaluating” or “indicative for” broadly encompass mental activity such as making conclusions or observations. Claim 12 also recites mathematical calculations. As such, the claims are also directed to recitations of abstract ideas. It is therefore determined that the claims are directed to judicial exceptions.
The claims are then analyzed to determine whether they recite an element or step that integrates the JE into a practical application (STEP 2A, prong 2) [Vanda Pharmaceuticals Inc., v. West-Ward Pharmaceuticals, 887 F.3d 1117 (Fed. Cir. 2018)].
The claims recite steps of providing a sample of blood, irradiating blood cells, performing cell lysis and using single cell gel electrophoresis. However this does not integrate the JE into a practical application because it is mere data gathering step to use the correlation and does not add a meaningful limitation to the method.
In the absence of steps or elements that integrate the JE into a practical application, the additional elements/steps are considered to determine whether they add significantly more to the JE either individually or as an ordered combination, to “’transform the nature of the claim’ into a patent eligible application” [Mayo Collaborative Services v. Prometheus Labs., Inc., 132 S. Ct. 1289, 1293 (2012), Alice Corp. Pry. Ltd. v. CLS Bank Int'l, 134 S. Ct. 2347 (2014)] (STEP 2B).
In the instant situation, the steps of providing a sample of blood, irradiating blood cells in the sample, performing cell lysis and using single cell gel electrophoresis are directed to the steps of the “comet” assay, which was well understood, routine, and conventional in the field years prior to the effective filing date of the invention, as evidenced by the art cited in applicant’s IDSs. See also, for example, the review taught by Speit (Speit and Hartmann, “The Comet Assay”, DNA REPAIR PROTOCOLS, 2nd ED, Human Press, 2006, pages 275-286), the teachings of Anderson (Anderson et al; WO2014/041340), and the teachings of McAuliffe (McAuliffe et al; Human Reproduction, vol 29, pages 2148-2155; 2014). Applicant is reminded that in Mayo, the Court found that “[i]f a law of nature is not patentable, then neither is a process reciting a law of nature, unless that process has additional features that provide practical assurance that the process is more than a drafting effort designed to monopolize the law of nature itself." Further "conventional or obvious" "[pre]solution activity" is normally not sufficient to transform an unpatentable law of nature into a patent-eligible application of such a law”. Flook, 437 U. S., at 590; see also Bilski, 561 U. S., at ___ (slip op., at 14) (“[T]he prohibition against patenting abstract ideas ‘cannot be circumvented by’ . . . adding ‘insignificant post-solution activity’” (quoting Diehr, supra, at 191–192)). The Court also summarized their holding by stating “[t]o put the matter more succinctly, the claims inform a relevant audience about certain laws of nature; any additional steps consist of well understood, routine, conventional activity already engaged in by the scientific community; and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately.” Therefore these limitations/steps do not “‘transform the nature of the claim’ into a patent-eligible application.’” Alice, 134 S. Ct. at 2355 (quoting Mayo, 132 S. Ct. at 1297).
When viewed as an ordered combination, the claimed limitations are directed to nothing more than the determination that a natural correlation/phenomena exists. Any additional element consists of using well understood, routine and conventional activity, and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately.
Accordingly, it is determined that the instant claims are not directed to patent eligible subject matter.
Claim Rejections - 35 USC § 112
112(a)
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.
Claims 1-12 are rejected under 35 U.S.C. 112(a) 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.
There are many factors to be considered when determining whether there is sufficient evidence to support determination that a disclosure does not satisfy the enablement requirements and whether any necessary experimentation is undue. These factors have been described by the court in In re Wands, 8 USPQ2d 1400 (CA FC 1988). Wands states at page 1404,
“Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex parte Forman. They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.”
The claims broadly encompass methods of determining the resistance of genomic DNA against damage by any type of radiation where an increased resistance of the genomic DNA is indicative for a proliferative disease or increased susceptibility for a proliferative disease.
The invention is in a class of inventions which the CAFC has characterized as 'the unpredictable arts such as chemistry and biology" (Mycolgen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Federal Circuit 2001)).
The specification teaches that the underlying biological principle is that genomic DNA of healthy individuals and cancer patients react differently to radiation, such as electromagnetic radiation (page 2). While the specification teaches that DNA sensitivity to damage by radiation is described in Anderson (Anderson et al; 2014/041340), the specification states “the inventors could show that the correlation is reverse”. The specification asserts that using the method of the present invention, it could be shown that healthy surrogate cells, such as PBMCs, from healthy subjects have higher sensitivity to electromagnetic radiation compared to healthy surrogate cells from cancer patients (page 2, last paragraph). At page 10, the specification states that genomic DNA of blood cells of cancer patients is better protected against UVB damage than cells from healthy individuals, but that there is no definite scientific rational explanation for this difference. The specification provides various hypothesis for the likelihood of the finding, including the time point of measurement in relation to the DNA damage response network of the individual with or without cancer.
At pages 12-13, the specification teaches that the step of determining genomic DNA damage comprises evaluation of DNA tail Normalized (DTN). While the specification states it is possible to use algorithms to determine and compare the absolute difference between healthy people and cancer patients, the specification does not teach any particular algorithms for the analysis. At page 16, the specification teaches an experimental protocol:
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The specification teaches that variation in timepoint of irradiation, either before or after introduction of cells into agarose gel was tested for 5 healthy subjects and 5 subjects with lung cancer and that diagnostic outcome was the same. However the specification does not teach how to evaluate the diagnostic outcome.
While the basis of the comet assay discussed in the instant specification was known in the art prior to the invention, the specification acknowledges that a different outcome was achieved in terms of analysis of the DNA damage of healthy blood cells from those of cancer patients. While the specification cites Anderson as an assay which used irradiation of blood cells to detect resistance or susceptibility of DNA to damage, the specification acknowledges that the prior art found the reverse result. Also, Sharpe (Sharpe et al; WO2008/050134) teaches assessment of the susceptibility of lymphocyte DNA to damage from irradiation with UV light using the comet assay. Sharpe notes that there was a significant difference between the response to UV irradiation based on skin type of normal patients and melanoma patients (pages 18-19). Notably, Sharpe acknowledges “anomalous data” included one skin type displaying genomic response similar to that of a melanoma patient’s response and that variability in response between different skin types may be due to genes resulting in an increased sensitivity to UV irradiation. Therefore, it appears that different factors exist which may affect the outcome of the assay and the determination of genomic DNA resistance or sensitivity against damage by radiation.
In the instant situation, it is clear that the specification concludes from the experimentation conducted, that genomic DNA from blood cells is more resistant to damage by radiation in cancer patients than in non cancer patients. However, given that similar assays have reached the opposite conclusion, it is not clear what parameters led to the results taught in the instant specification. It is not clear if the types of samples used, the stage of cancer patients, or if the type of cancer affected the results. It is not clear if particular experimental parameters or algorithms are critical for reproducibility of the results noted in the specification. The specification only teaches analysis of 5 lung cancer samples and 5 healthy controls. No information is provided for the patients in terms of stage of cancer. Furthermore, the specification does not teach if the results can be extrapolated to any type or stage of cancer. Without such guidance, the skilled artisan would be required to practice undue trial and error experimentation to determine if the results are reproduceable and if so, which parameters are required to predictably identify any proliferative disease, or cancer, based on the resistance of genomic DNA in blood cells to damage by radiation.
112(b)
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.
Claims 1-6 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention.
Claims 1-4 recite a use however no active steps are stated. Additionally, claims 5-6 depend from claims 1-4, and while a step is recited in each, it is not clear how the steps further limit a presumed method which itself has no steps. Accordingly, the metes and bounds of the claims are unclear.
Claim Rejections - 35 USC § 102
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 1-10 and 12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Anderson (Anderson et al; WO2014/041340).
With regard to claims 7 and 9, Anderson teaches obtaining whole blood from a subject, exposing the the blood to different levels of electromagnetic radiation (UV), and determining the level of damage and comparing to predetermined values (see pages 4-6). Anderson teaches that blood cells are lysed after having been exposed to radiation. Anderson teaches that DNA damage is assessed using single cell gel electrophoresis (the comet assay, pages 8-9). With regard to claim 8, it is noted that the elements are recited in a “wherein” clause and do not recite any active steps that distinguish the claims from the teachings of Anderson. With regard to claim 10, Anderson teaches that following irradiation, the slides are immersed in a container with cold lysing solution, therefore Anderson inherently teaches cell lysis less than 7 minutes following irradiation because Anderson teaches that following irradiation, the slides are immersed in a container with cold lysing solution (see page 8). With regard to claim 12, Anderson teaches that % tail DNA is used for statistical analysis (page 9). Anderson teaches that the method is used to screen for cancers including skin, lung, breast, bowel, prostate, and colorectal cancer. With regard to claims 1-6, the teachings of Anderson are taken to anticipate the claims since the claims do not set forth any clear active steps. The multiple slides taught by Anderson are taken as “at least one further biomarker”.
Claims 1-10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sharpe (Sharpe et al; WO2008/050134).
With regard to claims 7 and 9, Sharpe teaches obtaining lymphocytes from a subject, exposing the the cells to different levels of electromagnetic radiation (UV), and determining the level of damage and comparing to predetermined values (see pages 20-23). Sharpe teaches that blood cells are lysed after having been exposed to radiation. Sharpe teaches that DNA damage is assessed using single cell gel electrophoresis (3D comet assay). With regard to claim 8, it is noted that the elements are recited in a “wherein” clause and do not recite any active steps that distinguish the claims from the teachings of Anderson. With regard to claim 10, Sharpe teaches that following irradiation, the slides are transferred to a lysing solution, therefore Sharpe inherently teaches cell lysis less than 7 minutes following irradiation because Sharpe teaches that following irradiation, the slides are transferred to a lysing solution. With regard to claims 1-6, the teachings of Sharpe are taken to anticipate the claims since the claims do not set forth any clear active steps. The multiple assays taught by Anderson are taken as “at least one further biomarker”.
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 11 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over the Anderson (Anderson et al; WO2014/041340) and Sharpe (Sharpe et al; WO2008/050134).
The teachings of Anderson and Sharpe are set forth above and incorporated herein. With regard to claim 11, although Anderson and Sharpe, each individually exemplify an assay using UVA irradiation, Sharpe does teach that the UV radiation source may emit both UVA and UVB light or either UVA or UVB only. Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date to have also determined the susceptibility or resistance of DNA to damage by UVB irradiation because Sharpe teaches to do so, With regard to claim 12, although Sharpe teaches analysis of comet tail moment, Anderson teaches analysis using DNA tail percent. Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date, to have analyzed the DNA tail percent as taught by Anderson, in the method of Sharpe because Anderson exemplifies it use in analysis of data using the comet assay.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 12,270,783 in view of Anderson and Sharpe.
The claims of the ‘783 patent are directed to detecting DNA damage from cells by depositing a liquid sample comprising cells in a spot on a carrier plate, performing gel electrophoresis, and determining DNA damage. The claims do not teach providing a sample containing blood cells, irradiating the blood cells, or performing cell lysis. However, With regard to claims 7 and 9, Anderson teaches obtaining whole blood from a subject, exposing the the blood to different levels of electromagnetic radiation (UV), and determining the level of damage and comparing to predetermined values (see pages 4-6). Anderson teaches that blood cells are lysed after having been exposed to radiation. Anderson teaches that DNA damage is assessed using single cell gel electrophoresis (the comet assay, pages 8-9). With regard to claim 8, it is noted that the elements are recited in a “wherein” clause and do not recite any active steps that distinguish the claims from the teachings of Anderson. With regard to claim 10, Anderson teaches that following irradiation, the slides are immersed in a container with cold lysing solution, therefore Anderson necessarily teaches cell lysis less than 7 minutes following irradiation because Anderson teaches that following irradiation, the slides are immersed in a container with cold lysing solution (see page 8). With regard to claim 12, Anderson teaches that % tail DNA is used for statistical analysis (page 9). Anderson teaches that the method is used to screen for cancers including skin, lung, breast, bowel, prostate, and colorectal cancer. Further, Sharpe teaches obtaining lymphocytes from a subject, exposing the the cells to different levels of electromagnetic radiation (UV), and determining the level of damage and comparing to predetermined values (see pages 20-23). Sharpe teaches that blood cells are lysed after having been exposed to radiation. Sharpe teaches that DNA damage is assessed using single cell gel electrophoresis (3D comet assay). Additionally, Sharpe teaches UV radiation source may emit both UVA and UVB light or either UVA or UVB only. Therefore, it would have been prima facie obvious to the ordinary artisan to use the method of the ‘783 claims to assess DNA damage by irradiation as taught by Anderson and Sharpe because Anderson and Sharpe teach the importance of assessing DNA damage in cancer detection.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to examiner Jehanne Sitton whose telephone number is (571) 272-0752. The examiner is a hoteling examiner and can normally be reached Mondays-Fridays from 8:00 AM to 2:00 PM Eastern Time Zone.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Winston Shen, can be reached on (571) 272-3157. The fax phone number for organization where this application or proceeding is assigned is (571) 273-8300.
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/JEHANNE S SITTON/Primary Examiner, Art Unit 1682