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 .
Detailed Action
Summary
This is the Final Office Action based on application 16/483714 response filed 10/02/2026.
Claims 1 & 24-26, 36, 40 & 55-64 have been examined and fully considered.
Claims 2-17, 27-35, 37-39, and 41-46 and & 47-54 are cancelled.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, orcomposition of matter, or any new and useful improvement thereof, may obtain a patenttherefor, subject to the conditions and requirements of this title.
Claim 1 & 24-26, 36, 40 & 55-64 are rejected under 35 U.S.C. 101 because they are determined to be directed to a natural correlation and abstract idea without significantly more. The rationale for this determination is explained below:
As instantly claimed in Claims 1 & 24-26, 36, 40, & 55-64, applicant is detecting a level of C4c and CYFRA 21-2 and CRP “obtaining,” cross sectional images of the lungs, and the either use it to screen for lung cancer or classify an indeterminant lung nodule. The claims encompass both an abstract idea and also a natural correlation/law of nature judicial exception. Nothing claimed instantly that makes the measured compounds or the correlation significantly more than the judicial exception (natural correlation/law of nature-if a person was sitting around with a level of c4c in them, they would have the same cancer state as being claimed), nor is there anything which takes the information from the judicial exception and practically applies it ( as shown by law of what is considered practical application).
With respect to the three-step inquiry for 101 guidance:
Step 1: Whether the claims fall within any statutory category
Yes, independent Claims 1 & 57 are both drawn towards methods.
Step 2A, Prong 1: Whether the claim/s recites a judicial exception
Independent Claims 1 & 57 recite the judicial exception of a natural correlation/law of nature & abstract idea which is detecting the level of the natural compound of c4c and identifying the patient as having lung cancer if the level is a certain level and not having cancer if it is at another level.
Claim 1 also recites the abstract idea of, “classifying,” in both the claim preamble and the claim body, however the classifying is related to whether the patient have stage I or II lung cancer, so even though the word “diagnosis,” is not used, that is what is being done. Classifying and screening are also mental processes which are abstract ideas. Diagnoses based on biomarkers(c4c, CYFRA 21-2 and CRP) (being greater or lower than the level found in a control)- which is what is being done instantly are natural correlations which are law of nature judicial exceptions.
Claim 57 recites the abstract idea of “screening,” in the preamble and “classifying,” and “identifying,” in the claim body which are mental processes which are abstract ideas. to a reference which are mental processes/abstract ideas. The screening, classifying, and identifying are related to whether the patient have stage I or II lung cancer, so even though the word “diagnosis,” is not used, that is what is being done. Diagnoses based on biomarkers (c4c, CYFRA 21-2 and CRP) (being greater or lower than the level found in a control)- which is what is being done instantly are natural correlations which are law of nature judicial exceptions.
Step 2A, Prong 2: Whether the claims as wholes integrate the recited judicial exceptions into a practical application of the exception.
The answer to this for Claims 1 & 57 is no.
For claim 1, in addition to the claimed steps which are judicial exceptions as shown above, the below is claimed:
obtaining cross sectional images of the lungs, which are machine generated (from a patient who is asymptomatic for Stage I or II lung cancer)
detecting an indeterminant lung nodule on the cross sectional image
detecting C4c, CYFRA 21-2 and CRP level in plasma or serum of the subject.
Obtaining images, as generally claimed can reading on someone handing a doctor and image, or the image being provided to view/visually detect to a doctor on a computer. Therefore, the claimed “obtaining,” and “detecting,” can read on mental process/abstract ideas through broadest reasonable interpretation.
That the imaging is “machine generated,” does not change matters and no actual imaging is required in the claim given how obtaining and detecting can be interpreted. Further, even if a positive imaging step were required to be done by a machine---- this is considered to be data gathering to perform the judicial exception and therefore is insignificant extra-solution activity and does not practically apply the judicial exception. See MPEP 2106.05(g).
The claimed detecting of c4c, CYFRA 21-2 and CRP level in plasma or serum of patient is interpreted similarly. Especially at the level of generality claimed, this detecting this is considered to be data gathering to perform the judicial exception and therefore is insignificant extra-solution activity and does not practically apply the judicial exception. See MPEP 2106.05(g).
The final step of Claim 1 is “classifying,” the nodule found in one of the images as malignant in comparison to a sample that does not have stage I or II lung cancer, based on the level of c4c. This natural correlation--- level of c4c indicates whether a patient with an indeterminant nodule has lung cancer or not in comparison to a reference/control, is the claimed natural correlation judicial exception itself. It and “classifying,” are also mental processes (the natural correlation = a mathematical a comparison) which are abstract ideas.
Claim 1 also requires that “the subject is asymptomatic for Stage I or Stage II lung cancer,” and that a plasma or serum sample is used. The fact that the subject tested is asymptomatic and that the blood or plasma sample is from an asymptomatic subject, also does not practically apply the judicial exception. Again--- the sample used, is just used to perform data gathering to accomplish the judicial exceptions as shown above for the detecting of c4c step. Therefore, this is also considered to be insignificant extra-solution activity and therefore to not practically apply the judicial exceptions. See MPEP 2106.05(g).
Independent Claim 57 requires the same steps as Claim 1, for
obtaining cross sectional images of the lungs, which are machine generated (from a patient who is asymptomatic for Stage I or II lung cancer)
detecting a lung nodules which can be any of malignant, benign, or indeterminant on the cross sectional image
detecting C4c, CYFRA 21-2 and CRP level in plasma or serum of the subject.
For Claim 57 as in Claim 1, obtaining images, as generally claimed can reading on someone handing a doctor and image, or the image being provided to view/visually detect to a doctor on a computer. Therefore, the claimed “obtaining,” and “detecting,” can read on mental process/abstract ideas through broadest reasonable interpretation.
That the imaging is “machine generated,” does not change matters and no actual imaging is required in the claim given how obtaining and detecting can be interpreted. Further, even if a positive imaging step were required to be done by a machine---- this is considered to be data gathering to perform the judicial exception and therefore is insignificant extra-solution activity and does not practically apply the judicial exception. See MPEP 2106.05(g).
The claimed detecting of c4c, CYFRA 21-2 and CRP level in plasma or serum of patient is interpreted similarly. Especially at the level of generality claimed, this detecting this is considered to be data gathering to perform the judicial exception and therefore is insignificant extra-solution activity and does not practically apply the judicial exception. See MPEP 2106.05(g).
The final steps in Claim 57 of “classifying,” and “ the nodule found in one of the images as malignant in comparison to a sample that does not have stage I or II lung cancer, based on the level of c4c, and then “identifying,” the subject as having stage I or II lung cancer if one or more malignant modules are detected, is all judicial exceptions. The natural correlation--- level of c4c indicates whether a patient with an indeterminant nodule has lung cancer or not in comparison to a reference/control, is the claimed natural correlation judicial exception itself. “Identifying,” a patient as have the stage II or III lung cancer is a mental process based on the “classifying,” above, so it is also a judicial exception of an abstract idea.
Claim 57 also requires that “the subject is asymptomatic for Stage I or Stage II lung cancer,” and that a plasma or serum sample is used. The fact that the subject tested is asymptomatic and that the blood or plasma sample is from an asymptomatic subject, also does not practically apply the judicial exception. Again--- the sample used, is just used to perform data gathering to accomplish the judicial exceptions as shown above for the detecting of c4c step. Therefore, this is also considered to be insignificant extra-solution activity and therefore to not practically apply the judicial exceptions. See MPEP 2106.05(g).
Further--- for both Claims 1 & 57, nothing is claimed after the final claim step wherein lung cancer is diagnosed/identified or classified, such as a particular treatment.
Step 2B: Do the claims recite any elements which are significantly more than the abstract idea?
The answer for Claims 1 & 57 is no.
Both independent Claims 1 & 57 require the same steps in addition to the judicial exceptions identified above. They are:
obtaining cross sectional images of the lungs, which are machine generated (from a patient who is asymptomatic for Stage I or II lung cancer)
detecting a lung nodule/s based on the cross sectional image
detecting C4c, CYFRA 21-2 and CRP level in plasma or serum of the subject.
The obtaining images, or “machine generated,” images and instantly claimed, especially at the level of generality claimed is well understood, routine and conventional (WURC). Things which are WURC are not considered to add significantly more to a judicial exception. Further, as generally claimed the claimed detecting of the image can reading on someone handing a doctor and image, or the image being provided to view/visually detect to a doctor on a computer. Therefore, the claimed “obtaining,” and “detecting,” can read on mental process/abstract ideas through broadest reasonable interpretation. See MPEP 2106.05 (d) for what is considered WURC and “laboratory techniques as well-understood, routine, conventional activity.”
That this element is WURC is evidenced by KEARNEY in US 20130217057 who teaches of using CT scanning imaging for one or more images by a CT machine- which spit out cross sectional images (paragraph 0002, 0005, 0027, 0053, 004, 0098, 0025, Claim 5).
The claimed detecting of c4c, CRP, and CYFRA 21-1 and level in plasma or serum of patient is interpreted similarly. Especially at the level of generality claimed, general detecting, of c4c is WURC—see the prior art rejection below for teaching of this. Using plasma samples (from subjects who don’t have cancer versus ones that do) is also something that is WURC in the art, so does not add significantly more. See MPEP 2106.06 (d).
That detecting these biomarkers is WURC is evidenced by PILELY in “A specific assay for quantification of human C4c by use of anti-c4c monoclonal antibody” in view of KEARNEY in US 20130217057 and further in view of JAMES in US 20150072890.
PILELY teaches of detection method using monoclonal antibody (mAb) that is able to detect fluid phase C4c fragment without interference from other products generated from the complement component C4(full-length) (as is done instantly). Specifically, PILELY teaches of c4c Mab 99-72-18 (Figure 1 description & 2.3, first paragraph, 2.6, second paragraph).
KEARNEY teaches of using the specific biomarkers prolactin (Table 2) and CRP (Table 6) as biomarkers.
JAMES teaches of a method for detecting a biomarker panel as associating it with lung cancer (abstract). JAMES further teaches of detecting CYFRA 21-1, prolaction, and CRP (paragraph 0087, 0014, 0007, 0090) in serum or plasma(paragraph 0041) and determining the differential expression(higher or lower) of these markers (paragraph 0008, 0045). It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention to detect CYFRA 21-1 as is done in JAMES in the other pieces of prior art due to the advantage it has in being a tumor markers ( JAMES, paragraph 0091).
Further, in Claims 1 & 57 “classifying,” and “the nodule found in one of the images as malignant in comparison to a sample that does not have stage I or II lung cancer, based on the level of c4c, and/or then “identifying,” the subject as having stage I or II lung cancer if one or more malignant modules are detected, is all judicial exceptions. The natural correlation--- level of c4c indicates whether a patient with an indeterminant nodule has lung cancer or not in comparison to a reference/control, is the claimed natural correlation judicial exception itself. “Identifying,” a patient as have the stage II or III lung cancer is a mental process based on the “classifying,” above, so it is also a judicial exception of an abstract idea. Therefore, these are part of the judicial exceptions themselves and therefore do not add significantly more.
The dependent claims undergo a similar analysis.
Claim 24-26 & 58-60, specify further the rules for the diagnosis (which is a natural correlation and abstract idea), to that prolactin is also detected and the type of cancer and biomarkers detected. These are all parts of the natural correlation itself, and therefore not significantly more at step 2B nor a practical application at Step 2A/2.
With respect to Claims 36 & 61, it is specified that a CT scanner is used as the imaging machine. While a CT scanner is a machine, it does not solve the problems above. CT imaging still reads as insignificant extra solution activity and also can be interpreted from the claim which it depends from as just getting an obtained CT image. Further- even if the CT scan is performed, it is done for data gathering so is insignificant extra solution activity and therefore does not practically apply at Step 2A/2. Further using CT images is WURC and therefore does not add significantly more at Step 2 B.
In Claims 56 & 64 it is claimed that an immunoassay is performed using ELISA. At this time- these things are claimed a such a level of generality that they are WURC and therefore do not add significantly more at Step 2B. Also, at the level of generality claimed, is just used for data gathering so does not practically apply at Step 2A/2.
Claims 40, 55, 62-63, read the same as USPTO eligibility example 29, Claim 2. Anti-c4c does not practically apply the judicial exception at step 2A/2 and is WURC, so does not add significantly more at step 2B. Detection of c4c and it’s correlation with the claimed identifying and classifying is part of the judicial exception itself.
See MPEP 2106.04 & 2016.05.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
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 non-obviousness.
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 & 24-26, 36, 40 & 55-64 are rejected under 35 U.S.C. 103 as being obvious over MANGUERRA in US 20150099656 in view of PILELY in “A specific assay for quantification of human C4c by use of anti-c4c monoclonal antibody” in view of KEARNEY in US 20130217057 and further in view of JAMES in US 20150072890.
With respect to Claim 1, 24 & 57-59, MANGUERRA et al. teaches of methods and kits for the early detection of pathogens, precise identification of the etiologic agent, and improved disease surveillance (abstract). MANGUERRA et al. more specifically teach of detecting cancer (paragraph 0071, 0073, 0272), and of detecting both prolactin (paragraph 0073) and C4c (paragraph 0078) and of using lung cells (so detecting cancer in lung cells) (paragraph 0320) and of detecting in comparison to a control value/reference sample from a healthy subject (paragraph 0310). MANGUERRA et al. further teach of the present invention relates to an in vitro method for diagnosing at least one target disease in a subject, said target disease being known to induce the synthesis of at least one target antibody in said subject, comprising performing the immunoassay of the invention, wherein said subject is diagnosed to be suffering from said at least one target disease if the amount of said at least one target antibody is higher than a control value (paragraph 0306).
MANGUERRA et al. teach of using malignant or normal non-malignant samples (paragraph 0157)
Though teaching of detection of c4c, MANGUERRA does not teach specifically of c4c “fragment,” so PILELY is used to remedy this,
PILELY et al. teach of detection method using monoclonal antibody (mAb) that is able to detect fluid phase C4c fragment without interference from other products generated from the complement component C4(full-length) (as is done instantly). Specifically, PILELY teaches of c4c Mab 99-72-18 (Figure 1 description & 2.3, first paragraph, 2.6, second paragraph). PILELY also teaches of detecting a level of C4c that is higher than a control (Page 92, 3.4).
The C4c specific mAb was tested in different enzyme-linked immunosorbent assay (ELISA)(immunoassay) combinations with various types of in vitro activated sera and samples from factor I deficient patients. The specificity of the mAb was further evaluated by immunoprecipitation techniques and by analysis of eluted fragments of C4 after immunoaffinity chromatography. The anti-C4c mAb was confirmed to be C4c fragment specific, as it showed no cross-reactivity with native (un-cleaved) C4, C4b, iC4b, or C4d fragments. Also, no reaction was observed with C4 fragments in factor I deficient plasma or serum samples(abstract).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention to detect c4c “fragment,” as is done in PILELY in the method of MANGUERRA due to the advantage and promise complement system biomarkers and c4c fragment specifically show as tools for pathogenesis (PILELY, abstract).
Since MANGUERRA et al. call out cancers, but do not specifically call out the phrase “lung cancer”, or teach of using nodules, and further MANGUERRA and PILELY do not teach of associated imaging or lung cancer detection or stage screening/identification/classification, KEARNEY is used to remedy this. MANGUERRA and PILELY also do not teach of detection of CRP and CYFRA 21-1.
KEARNEY et al. teaches of the patient having primary malignant nodules or non-malignant nodules (Table 7, 8, paragraph 0004, 0027). KEARNEY et al. also teach of the cancer being small cell or non-small cell (Table 8) and of the subject being at risk for lung cancer (paragraph 0007).
KEARNEY also teach of screening/ classifying/identifying the stage of cancer which can be any of stages I-IV (paragraph 0027, 0057, Table 6) and that the patient which CT imaging is performed for can be asymptomatic (paragraph 0002).
KEARNEY et al. teach of a method to diagnose or classify a subject as having lung cancer or a non-cancerous condition, and to distinguish between different types of cancer e.g., malignant versus benign, SCLC versus NSCLC stages) (abstract). KEARNEY et al. also teach of using the specific biomarkers prolactin (Table 2) and CRP (Table 6) as biomarkers and of comparison to controls based on differential (higher or lower than control) expression (paragraph 0125, 0006).
KEARNEY et al. further teach of these methods finding use in screening methods for lung conditions, and particularly lung cancer diagnostics. More importantly, the invention finds use in determining the clinical management of a patient. That is, the method of invention are useful in ruling in or ruling out a particular treatment protocol for an individual subject, and in therapeutic drug monitoring/selection which make the instant methods obvious to screen or monitor treatments by biomarker levels (paragraph 0029, 0053-0054, 0068, 0108, 0110), and specifically of determining biomarker levels by immunoassay (paragraph 0093). KEARNEY et al. also teach of the detection of C4 detection of lung cancer (would include C4c fragment). Kearney et al. teach of C4BPA and of detecting C4 lung cancers (which would include c4c fragment protein as claimed) (Table 6). KEARNEY et al. further teach of using CT scanning imaging for one or more images by a CT machine- which spit out cross sectional images (paragraph 0002, 0005, 0027, 0053, 004, 0098, 0025, Claim 5). KEARNEY et al. further teach of detecting the patient having primary malignant nodules or non-malignant nodules (Table 7, 8 paragraph 0004, 0027). It would have been obvious before the effective filing date of the instant invention to one of ordinary skill in the art to diagnose lung cancer as is done in KEARNEY in the cancer diagnostic method of MANGUERRA and PILEY due to the need in the art for better diagnostics for lung cancer conditions (KEARNERY, paragraph 0004).
Further- regarding the claimed order of performing the claimed imaging and determining/measurement steps for C4c- in many places applicant claims that these steps can be performed in any order. Therefore, it would be obvious to one of ordinary skill to change these, step around dependent on availability of imaging machine or assay labs. Further—See MPEP 2144.04 In reBurhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946) (selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results).
Further, it would have been obvious to one of ordinary skill in the art to screen the stage of cancer as is done in KEARNEY in the methods of MANGUERRA and PILELY due to the advantage this offers in making a pathological interpretation (Table 8).
KEARNEY, MANGUERRA and PILELY also do not teach of detection of CYFRA 21-1 in association with the other biomarkers to diagnose lung cancer.
JAMES is used to remedy this and teaches of a method for detecting a biomarker panel as associating it with lung cancer (abstract). JAMES further teaches of detecting CYFRA 21-1, prolaction, and CRP (paragraph 0087, 0014, 0007, 0090) in serum or plasma(paragraph 0041) and determining the differential expression(higher or lower) of these markers (paragraph 0008, 0045). It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention to detect CYFRA 21-1 as is done in JAMES in the other pieces of prior art due to the advantage it has in being a tumor markers ( JAMES, paragraph 0091).
With respect to Claims 25-26, 59, KEARNEY teach of the cancer being small cell or non-small cell (Table 8) and of the subject being at risk for lung cancer (paragraph 0007).
With respect to Claim 60, PILEY and MANGUERRA teach of the above, but do not teach of the claimed smoking history. KEARNEY is used to remedy this. KEARNEY teaches of the patients having a 30 year smoking history (paragraph 0081), and of monitoring age as well (Table 8), with the age median being 65 (Table 17). It would have been obvious to one of ordinary skill to use patients in these grouping as is done in KEARNEY in the methods of PILEY and MANGUERRA due to the fact that these groups are known to be associated with lung cancer risk (KEARNEY, paragraph 0081).
With respect to Claims 36 & 61, KEARNEY et al. teach of using CT scanning imaging (paragraph 0002, 0005, 0027, 0053, 004, 0098, 0025, Claim 5).
With respect to Claim 40, 55-56, 62-64, PILEY et al. teach that the C4c specific mAb was tested in different enzyme-linked immunosorbent assay (ELISA)(immunoassay) combinations with various types of in vitro activated sera (serum) and samples from factor I deficient patients(abstract). PILEY further teaches of using anti-C4c mAb was confirmed to be C4c fragment specific, as it showed no cross-reactivity with native (un-cleaved) C4, C4b, iC4b, or C4d fragments. Also, no reaction was observed with C4 fragments in factor I deficient plasma or serum samples(abstract). PILEY et al. teach that the C4c (complement component C4c) specific mAb (monoclonal antibody) was tested in different enzyme-linked immunosorbent assay (ELISA)(immunoassay) combinations with various types of in vitro activated sera and samples from factor I deficient patients(abstract). See reason for combination from above.
Response to Arguments
Applicant's arguments filed 10/02/2026 have been fully considered but they are not persuasive.
With respect to the 101 rejection, applicant has amended the claims significantly on 10/02/2026, however nothing was added to the claims which practically applies the judicial exception at step 2A/2 nor which adds significantly more at step 2B. Therefore, these amendments are addressed in the 101 rejection as shown above. All claimed remain rejected under 101.
With respect to the 101 rejection, applicant argues that the instant claims as a whole neither set forth or recite a judicial exception. The examiner disagrees with this and the reasoning for this is outlined in the 101 rejection above. Applicant argues that the claims should not be rejected under 101 since the claims recited obtaining cross sectional images of a subject lungs and classifying based on these images and a comparison to a control, is also not naturally occurring. With respect to this--- the examiner notes that the taking of images is data gathering as outlined in the rejection above, and the classifying and comparison themselves are mental process abstract ideas, which in fact are judicial exceptions. Nothing about data gathering, nor adding another type of judicial exception to the claims do anything to make the claims patent eligible. This is true especially at the level of generality claimed.
Applicant argues that “the human mind by itself is not capable detecting levels of C4c fragment and CYFRA 21-1 and CRP.” The examiner notes that this is not what the examiner said, but instead that the determining of these levels is done only for data gathering to accomplish the judicial exceptions of classifying and screening for lung cancer. Data gathering to accomplish the judicial exceptions is found to be insignificant extra-solution activity and therefore does not practically apply the judicial exceptions at step 2A/2. Further, especially at the level of generality claimed both determining the amounts of the biomarkers by cross sectional imaging, AND in serum or plasma is well understood, routine and conventional (WURC). Things which are WURC are not found to be significantly more than claimed judicial exceptions at step 2B. See MPEP 2106.05 (d).
Applicant argues with respect to the 101 rejection that obtaining the cross sectional image relies upon obtaining a machine generated cross section image and that the human mind is not capable of obtaining these images. Again--- the examiner notes that the examiner has not said that the human mind would take these images, but instead that the imaging is done for data gathering so does not practically apply and also is WURC so does not add significantly more. Notably, the test for determination of eligible claims is not whether they require a machine or not, which seems to be what applicant is arguing. It is noted to this affect too, that in fact no even generic machine is actually claimed—though adding such a generic machine would not help matters here.
Applicant also argues the further specification in amendments dated 10/02/2026 of the molecular signal to include not only c4C but also CYFRA 21-1 and CRP and that the claimed obtaining imaging practically applies the judicial exception and that these steps are not well known. The examiner adamantly disagrees, and maintains that the addition of biomarkers to the molecule signal is further specifying the natural correlation judicial exception itself (biomarker/s level comparison to reference = disease or disease stage). Further, it is shown in the 101 rejection with evidence from prior art that the extra steps in addition to the claimed judicial exceptions themselves, of imaging and detecting are in fact well known. Therefore, there is no claimed practical application nor is significantly more claimed and all pending claims remain rejected under 101.
With respect to the 103 prior art rejection applicant argues that none of the prior art references used individually, Manguerra, Pilely, or Kearney teach of the claimed inventions by themselves.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Further, applicant argues that the claims do not teach of the newly amended subject matter including biomarker CYFRA 21-1. Applicant’s arguments with respect to claim(s) have been considered but are moot because the new ground of rejection does not rely on the combination of references applied in the prior rejection of record for any teaching or matter specifically challenged in the argument. Specifically, the newly used JAMES reference teaches of this as shown in the above rejection.
Applicant also argues that MANGUERRA does not teach of detecting cancer, but instead teaches of detecting antibodies. While yes, the examiner see where MANGUERRA teaches of antibody detection, they aalso do in fact teach of detection of cancer (paragraph 0003, 0071, 0073, 0272).
With respect to the MANGUERRA and PILELY references, applicant argues that the references do not teach of detecting c4c fragment, specifically for lung cancer. The examiner maintains that PILELY does in fact specifically teach of this detection of c4c(abstract) and it being a marker for inflammatory diseases (of which cancer) is one of--- as shown in the above rejection.
Applicant specifically argues that Pilely does not teach of lung cancer detection/prognosis (which is what the instant claims are drawn towards). The examiner see this, but would like to point out that this is in fact why MANGUERRA and KEARNEY were used. Further- PILELY does in fact recognize the complement systems of which C4 is part are therefore potential biomarkers for any acute and chronic inflammatory diseases—of which cancer is known to be one of (PILEY, Page 88, column 1, paragraph 1).
Applicant argues that Manguerra does not teach of C4c detection specific to lung cancer, but instead mentions it in relation to autoimmune disease and that the overall reference is more specific to methods for detecting target antibodies and kits for this.
With respect to this, though the examiner sees that the specific mention of C4c(fragment) in Manguerra is with respect to autoimmune disease (paragraph 0078) however, the rest of the reference makes it clear that cancers and autoimmune diseases are often and can be detected by the same antibody compounds (Manguerra, paragraph 0003 & 0272). Therefore, the examiner disagrees with applicant and maintains that the combination of PILELY, MANGUERRA, and KEARNEY with the addition of JAMES to the instantly amended claims to make the instant invention obvious.
With respect to Kearney, applicant argues that again that Kearney does not teach of using C4c for detection for lung cancer detection. With respect to this- the examiner would like to point out that C4c detection was already taught by PILELY and a 103 rejection was made and therefore KEARNEY does not have to.
Further- KEARNEY et al. still does in fact teach of detecting C4 fragments and the association with cancer. Specifically, Kearney et al. teach of the detection of C4b- and it’s association with lung cancer (Table 6). Since C4b is a fragment of C4 as is the claimed C4c--- the teaching in KEARNEY teaches of detecting generally a C4 associated cancer- lung cancer (which would include c4c fragment protein as claimed)(Table 6). Applicant argues that this is not a teaching of the C4c fragment specifically and the examiner agrees, but maintains that C4c detection for inflammatory disease conditions was already taught above by PILELY.
Applicant also argues that KEARNEYS teaching of indeterminant nodules (paragraph 0004) would not play a diagnostic role, since the subject can also have no nodules. The examiner disagrees with this, as in the case where there are nodules, they would absolutely have a diagnostic role and therefore, still read on the instant claims.
Applicant further argues that they do not think KEARNEY and MANGUERRA cure the purported deficiencies of PILELY and also that one would not be motivated to change the principle of operation or indication of PILELY or MANGUERRA and that there would be no reasonable expectation of success and that the office is using improper hindsight bias. The examiner has already responded to these above in that KEARNEY And MANGUERRA would not be changing the principle of operation or indication of PILELY since PILELY is specific to inflammatory disorders whether chronic or acute (which cancer is one of) and therefore the examiner is not using improper hindsight and that there would be reasonable expectation of success
The examiner disagrees with applicant’s arguments that are on record, and all claims remain rejected.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
COHEN in US 20180068083. COHEN teaches of methods and tests that measure biomarkers (e.g., tumor antigens) and collect clinical parameters from patients, and computer-implemented machine learning methods, apparatuses, systems, and computer-readable media for assessing a likelihood that a patient has a disease, relative to a patient population or a cohort population. In one embodiment, a classifier is generated using a machine learning system based on training data from retrospective data and subset of inputs (e.g. at least two biomarkers and at least one clinical parameter), wherein each input has an associated weight and the classifier meets a predetermined Receiver Operator Characteristic (ROC) statistic, specifying a sensitivity and a specificity, for correct classification of patients. The classifier may then be used to assess the likelihood that a patient has cancer relative to a population by classify the patient into a category indicative of a likelihood of having cancer or into another category indicative of a likelihood of not having cancer (abstract). COHEN further teaches of detecting lung cancer(paragraphs 0009-0012) by detecting CYFRA 21-1 and CRP and prolactin (paragraph 0127) and detecting differentially expressed levels thereof(paragraph 0087).
BORGIA in US 20140274772. BORGIA teaches of a method and kit for assessing lung cancer including detection of CRP and CYFRA 21-1(abstract, paragraph 0001, 0019, 0025) and also of comparison to control subjects and values (paragraph 0045) and also of determining differential (higher or lower) expression(paragraph 0019, 0021, 0023, 0034, 0038, 0041). BORGIA teaches that this is for detection of nodules and specifically in indeterminate nodules (paragraph 0002, 0011) and of using CT imaging (paragraph 0011). BORGIA further teaches that detection CYFRA 21-1 for determination of lung cancer, has association with imaging due to the advantage detecting biomarkers including CYFRA 21-1 and in determining malignancy in indeterminate nodules (BORGIA, paragraph 0005, 0006, 0011).
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to REBECCA M FRITCHMAN whose telephone number is (303)297-4344. The examiner can normally be reached 9:30-4:30 MT Monday-Friday.
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/REBECCA M FRITCHMAN/Primary Examiner, Art Unit 1758
