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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on November 10, 2025 has been entered. By way of this submission, Applicant has amended claim 31.
Claims 31-41 are pending in the application. Claims 40-41 remain withdrawn from consideration, pursuant to the Restriction Requirement mailed May 24, 2024.
Claims 31-39 are therefore under examination before the Office.
The rejections of record can be found in the previous Office action, dated September 12, 2025.
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 31-39 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. The claims recite a natural phenomenon, a correlation between biomarker levels and lung cancer. This judicial exception is not integrated into a practical application because the claimed data gathering steps do not add a meaningful limitation to the method as they are insignificant extra-solution activity. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because quantifying levels of a biomarker is a well-understood, routine, conventional activity in laboratory technique, and therefore insufficient to amount to an inventive concept.
The unpatentability of laws of nature was confirmed by the U.S. Supreme Court in Mayo Collaborative Services v. Prometheus Laboratories, Inc., No. 10-1150 (March 20, 2012). “Laws of nature, natural phenomena, and abstract ideas” are not patentable. Diamond v. Diehr, 450 U.S. 175, 185 (1981); see also Bilski v. Kappos, 561 U.S. 593,604, 95 USPQ2d 1001, 1007 (2010). “Phenomena 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). The Supreme Court does acknowledge that it is possible to transform an unpatentable law of nature, but one must do more than simply state the law of nature while adding the words “apply it.” Essentially, appending conventional steps, specified at a high level of generality, to laws of nature, natural phenomena, and abstract ideas cannot make those laws, phenomena, and ideas patent-eligible.
In Prometheus, the Court found that “[i]f a law of nature is not patentable, the 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.” Additionally, “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.: “[T]he prohibition against patenting abstract ideas ‘cannot be circumvented by’. . . adding ‘insignificant post-solution activity’” (quoting Diehr, 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.”
The first step under this guidance is determining if the claim is directed to one of the four statutory categories (process, machine, manufacture, or composition of matter). In this case, the claims are a method (process). The second step is determining if the claims recite or involve judicial exception(s), such as laws of nature, natural phenomena, natural products, or an abstract idea. In this case, the claims are drawn to “An in vitro or ex vivo method for detection or prognosis of lung cancer (LC) in a subject by determining qualitative and quantitative variation of an antigenic epitome associated with LC.” This is a natural correlation/observation of a natural phenomenon, the relationship between variation of an antigenic epitome and diagnosis of LC, which is a judicial exception. Furthermore, the judicial exception is not integrated into a practical application, as the claims do not rely on or use the exception in a further step. See MPEP 2106.04(d). Thus, it must be determined if the claim as a whole recites something significantly more than the judicial exceptions.
The elements other than the detection itself is contacting a sample from a subject with a panel of antibodies in an enzyme-linked immunosorbent assay (ELISA), a calculation of a probability of a presence or an absence of lung cancer, performing either low dose computed tomography (LDCT) or chest X-ray examination to confirm the probability of the presence or absence of lung cancer, and the use of phage display to identify epitope-antigens of interest.
The use of antibodies or immunoassays to determine levels of a biomarker has been characterized by the Court as “mere data gathering” and “insignificant extra-solution activity”. Determining the level of a biomarker in blood by any means has also been recognized by the courts as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity. Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017). MPEP 2106.05 (ID). Using this method to make such a diagnosis would have been a routine, conventional choice, and as such does not offer significantly more than the exception itself.
Additionally, the panel of antibodies used in the claimed methods were also well-known in the art to be useful for the detection of lung cancer, as the specification at para. 0438 and Applicant's remarks submitted April 14, 2025 state at page 13 that the antibodies used in the claimed method are from the Quantiplasma™ or Plasmascan™ commercially available libraries, which were known to be useful in lung cancer diagnosis (see, e.g., Kovacs (Electrophoresis. 2013 Nov;34(20-21):3064-71, cited previously).
Likewise, the use of LDCT is well understood, routine, and conventional in the diagnosis of lung cancer. For example, Wood (J Natl Compr Canc Netw. 2018 Apr; 16(4):412-441, cited previously) describes standard clinical practice guidelines in oncology for the diagnosis of lung cancer, and states that LDCT is recommended for detecting noncalcified nodules that may be suspicious for lung cancer (page 19).
The use of phage display for the identification of epitope-antigens of interest is also well-known in the art. Hajdu (Immunol Lett. 2014 Aug;160(2):172-7, cited in IDS) teaches that phage display is frequently used for mapping antibody epitopes (page 173, left column, third paragraph).
The calculation of a probability step of clause b) of claim 31 is merely a mental process that amounts to only an abstract idea. Calculation relies upon the application of a mathematical formula, and can be performed within the mind. MPEP 2106.04(a)(2). The mathematical models recited were also known in the art as conventional and well-understood for the purpose of disease diagnosis (see, e.g., James (US20150072890A1, cited previously)). As such, this step does not add "significantly more” to the exception.
The remaining claims further characterize the exception itself, e.g., additional details for measuring antibody-antigen interactions. These specifics are also a) directed to the data gathering step and b) routine choices when practicing the well-established assays for detecting antibody-antigen binding.
Applicant argues that the mimotope antigens used in the present invention are not found in nature, and the use of measuring the antigenic epitome variations to identify proteomic changes associated with lung cancer is not a well-understood, routine, conventional activity in laboratory technique.
Applicant's arguments have been considered fully but are not found to be persuasive.
The claims are not directed to the mimotopes themselves. The claims recite a method of detection or prognosis of lung cancer, which is a judicial exception. This method is performed by the assessment of biomarkers in blood plasma, which is mere data gathering by a well-known method. No manipulation of the mimotopes themselves is claimed. MPEP 2106.05(g).
Likewise, the use of phage display to screen for mimotopes is also mere data gathering by a well-known method (see Hajdu, page 173, left column, last paragraph). This step is also recited at a high level of generality in the claims.
Simply appending well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, is not sufficient to integrate the judicial exception into an inventive concept. Applicant's use of what is conventionally known and routinely practiced in the art does not reach the threshold of "significantly more". MPEP 2106.05.
This rejection is therefore maintained.
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.
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 31-39 were previously rejected under 35 U.S.C. 103 as being unpatentable over James (US20150072890A1) in view of Kovacs (Electrophoresis. 2013 Nov;34(20-21):3064-71) and Riel-Mehan (WO2013062515A2).
Applicant argues that the cited references do not teach every aspect of the claims as amended; specifically, the references do not teach a method for detecting, managing or monitoring lung cancer via plasma protein epitome profiling, or the sequences of the antigen epitopes, also referred to as mimotope peptides.
Applicant's arguments in view of the amendments to the claims have not addressed this issue fully. In the interest of compacting prosecution, the above rejection is withdrawn, and the following new grounds of rejection is issued, necessitated by Applicant's amendment to the claims:
Claims 31-39 are rejected under 35 U.S.C. 103 as being unpatentable over James (US20150072890A1) in view of Kovacs (Electrophoresis. 2013 Nov;34(20-21):3064-71), Riel-Mehan (WO2013062515A2), and Hajdu (Immunol Lett. 2014 Aug;160(2):172-7, cited in IDS).
James teaches methods of detecting lung cancer in a patient by assessing antigenic biomarkers in a sample from the patient (para. 0013). James further teaches that the presence and quantification of one or more antigens or antibodies in a test sample can be determined by ELISA (para. 0100-0101).
James further teaches that the sample may be blood plasma (para. 0041).
James further teaches comparing measured biomarker values to a standard or control (para. 0102).
James further teaches that the probability of cancer is calculated using standard statistical analysis, wherein the measurements of each lung cancer biomarker in the panel are combined to provide a probability of cancer by logistic regression analysis (para. 0130). James also teaches the use of Receiver Operating Characteristic curves to distinguish between populations with or without cancer (para. 0059-0061).
James further teaches the use of low-dose computed tomographic screening and chest x- ray for the early detection of lung cancer (para. 0004).
James further teaches that CA125 is a lung cancer biomarker (para. 0014), which is pertinent to claim 35.
James further teaches that ELISA is a “sandwich assay” (para. 0101), which is pertinent to claim 36.
James further teaches that this method has a specificity of 80%, and an area under the curve (AUC) value of 0.80 (para. 0033), which is pertinent to claims 38 and 39.
However, James does not teach the specific antibodies recited in the claims, or the identification of epitope-antigens with phage display.
Kovacs teaches the PlasmaScan™ and QuantiPlasma™ antibody libraries, and that said libraries are useful for screening for biomarkers of lung cancer (page 3065, left column, first paragraph). According to Applicant's specification at para. 0438, the panel of antibodies used in the claimed invention are found in the PlasmaScan™ and QuantiPlasma™ antibody libraries.
Riel-Mehan teaches that chest x-ray and low dose spiral computed tomography are useful in diagnosis of lung cancer (para. 0007).
Riel-Mehan also teaches the use of biomarkers for the detection and diagnosis of cancer (para. 0020). Riel-Mehan further teaches the use of ELISA as a method to detect an analyte (para. 0174-0175).
Riel-Mehan further teaches that a receiver operating characteristic curve is useful in assessing biomarkers (para. 0349).
Riel-Mehan further teaches comparison between gene expression levels of normal subjects and subjects suffering from a disease, or between various stages of the same disease (para. 0121).
Riel-Mehan further teaches that testing of biomarker levels in combination with evaluation of any additional biomedical information, such as routine imaging techniques, may improve sensitivity and specificity of lung cancer detection (para. 0127).
Riel-Mehan further teaches the use of labels (i.e., a labeled tracer) in the context of ELISA (para. 0162 and 0174), which is pertinent to claim 37.
Hadju teaches the use of phage display to identify and select for mimotopes (i.e., epitope-antigens specific for an antibody) (page 173, left column, last paragraph). Hajdu further teaches the use of ELISA in verifying binding of phage clones (page 173, right column, last paragraph).
Hadju further teaches that this method is useful in combination with an antibody library to perform assays of the subject's proteome (Figure 1).
Hadju further teaches that epitope profiling is useful in biomarkers associated with lung cancer (page 173, left column, second paragraph).
Hadju also teaches the PlasmaScan™ and QuantiPlasma™ antibody libraries (abstract).
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the teachings of James, Kovacs, Riel-Mehan, and Hadju to arrive at the claimed invention. As both James and Riel-Mehan teach, the evaluation of biomarkers in combination with imaging techniques such as chest x-ray and low dose spiral computed tomography were known to be useful for detection of lung cancer. Kovacs teaches the use of the PlasmaScan™ and QuantiPlasma™ antibody libraries to screen for biomarkers of lung cancer. Hadju teaches the use of phage display and ELISA to identify mimotopes of interest while screening an antibody library.
One of ordinary skill using said libraries to screen for biomarkers of lung cancer according to Kovacs, would therefore use all of the antibodies of the current claim, as evidenced by the instant specification. One of ordinary skill could use the antibodies of Kovacs in methods of James, Riel-Mehan, and Hadju to arrive at the claimed invention, with each component of the combination performing its known, usual function, and the combination would have yielded nothing more than predictable results.
The steps of the claimed method are recited using the open-ended transitional term "comprising", which does not exclude additional, unrecited elements or method steps. See, e.g., Mars Inc. v. H.J. Heinz Co., 377 F.3d 1369, 1376, 71 USPQ2d 1837, 1843 (Fed. Cir. 2004). MPEP 2111.03(I).
In response to Applicant's arguments, the preamble of the claim merely states the intended use of the invention without any limiting steps. If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020) (The court found that the preamble in one patent’s claim is limiting but is not in a related patent); Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See also Rowe v. Dror, 112 F.3d 473, 478, 42 USPQ2d 1550, 1553 (Fed. Cir. 1997) ("where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation"); Kropa v. Robie, 187 F.2d at 152, 88 USPQ2d at 480-81 (preamble is not a limitation where claim is directed to a product and the preamble merely recites a property inherent in an old product defined by the remainder of the claim). MPEP 2111.02(II).
Conclusion
No claim is allowed.
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/PETER JOHANSEN/Examiner, Art Unit 1644