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 Status
Claims 1-5, 14, 15, 17, & 22 filed on 07/06/2026 are pending. Claims 18-21, 23, & 25-27 are withdrawn from consideration as being drawn to a non-elected invention. Claims 2-4 are rejoined with are rejoined with Group I. Claims 1, 2, 5, 14, 15, 17, & 22 are currently under examination directed to the elected species of the particular combination of at least two biomarkers LEP and IL-17 in claims 1, 2, 5, 14, 15, 17, & 22 and of detection of specific H. pylori IgA and IgG antibodies in claim 15 (see response dated 01/13/2026). The cancellation of claims 9, 12, 16, & 24 in the reply filed 07/06/2026 is acknowledged. All the amendments and arguments have been thoroughly reviewed but are deemed insufficient to place this application in condition for allowance. The following rejections are either newly applied, as necessitated by amendment, or are reiterated. They constitute the complete set being presently applied to the instant application. Response to Applicant’s argument follow. This action is FINAL.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office Action.
Any rejection not reiterated is hereby withdrawn in view of the amendments to the claims.
Claim Rejections - 35 USC § 112
Claim 15 is 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.
Regarding claim 15, the claim recites the limitation “the patient” in lines 6 & 7 of the claim and there is insufficient antecedent basis for this limitation in the claim and it is unclear if “the patient” is meant to refer back to “a human patient” in claim 1, from which claim 15 depends, or is referring to a different patient.
Claim Rejections - 35 USC § 101
Claims 1-5, 14, 15, 17, & 22 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.
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 recites a method of determining whether a human patient has lesions rendering said patient at risk of a gastric cancer condition comprising determining a level of at least three biomarkers selected from a group, comparing the determined levels to a control, and if the levels of the at least three biomarkers deviate from the controls, concluding that the human patient has lesions rending the patient at risk of a gastric cancer condition and further conducting further medical testing for gastric cancer. This recitation is a natural correlation between levels of at least three biomarkers and risk of a gastric cancer condition. With regard to the natural correlation, as in Mayo, the relationship is itself a natural process that exists apart from any human action. The claimed invention also recites “determining the level of at least three biomarkers”, and “comparing the levels determined in step a. to a control”, and “conclusion is made that the human patient has lesions rendering the human patient at risk of a gastric cancer condition” which are recitations of an abstract idea because it encompasses conclusions and determinations which can occur entirely within the mind. 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 determining the level of at least three biomarkers selected from a group, comparing the levels to a control, and concluding that the patient is as risk for a gastric cancer condition if the determined levels of the at least three biomarkers deviate from their controls and further steps of conducting further medical testing for gastric cancer and of detecting a H. pylori infection, however this does not integrate the JE into a practical application because it is a 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 detecting the level of at least three biomarkers and comparing to a control are generally recited and do not provide any particular reagents that might be considered elements that transform the nature of the claims into a patent eligible application because no specific elements/steps are recited. This step is not only a mere data gathering step, but the general recitation of detection of known nucleic acids is well understood, routine, and conventional activity (See MPEP 2106.05(d)(II)). 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.
Response to Arguments
The response traverses the rejection. The response asserts that the invention involves determining the levels of specific biomarkers and using this information to determine risk for gastric cancer and whether the patient needs further medical testing for gastric cancer and that the pending claims recite “conducting further medical testing for gastric cancer selected from… and biopsies for histological examination” and in this way the claimed method provides a practical application that amounts to significantly more than the judicial exception. This argument has been thoroughly reviewed but was not found persuasive. First, the steps of determining the level of at least three biomarkers selected from a group, comparing the levels to a control, and concluding that the patient is as risk for a gastric cancer condition if the determined levels of the at least three biomarkers deviate from their controls and further steps of conducting further medical testing for gastric cancer and detecting a H. pylori infection, does not integrate the JE into a practical application because it is a mere data gathering step to use the correlation and does not add a meaningful limitation to the method. Further, the steps of detecting the level of at least three biomarkers and comparing to a control are generally recited and do not provide any particular reagents that might be considered elements that transform the nature of the claims into a patent eligible application because no specific elements/steps are recited. This step is not only a mere data gathering step, but the general recitation of detection of known nucleic acids is well understood, routine, and conventional activity (See MPEP 2106.05(d)(II)) and therefore does not ad significantly more to the judicial exception.
For these reasons, and the reasons already made of record and modified to address the claims as currently amended, the rejections are maintained and applied to the newly amended claims.
Claim Rejections - 35 USC § 103
Claim(s) 1, 2, 4, 17, & 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Capelle (Capelle et al.; Heliobacter, Vol. 14, pages 596-604, November 2009), as cited on the IDS dated 01/13/2026, in view of Severin (WO 2015/003945 A1, January 2015).
Regarding amended claim 1, Capelle teaches a method for to identify patients at high risk for gastric cancer through serum markers for gastric precursor lesions (determining whether a human patient has lesion rendering said patient at risk of a gastric cancer condition) comprising obtaining serum (blood) samples from patients susceptible to evolve into a gastric cancer condition and measuring the level of leptin (LEP), pepsinogen I and II, and gastrin markers (determining the level of at least three biomarkers comprising LEP), comparing the markers level with controls (comparing the levels determined in a. to a control), and analyzing to determine the predictive power of the markers in which significantly different levels of leptin (LEP) and pepsinogen I and II indicated intestinal metaplasia (lesion rendering the human patient at risk of a gastric cancer condition) (if levels of at least three biomarkers deviate from the levels of their controls, conclusion is made that the human patient has lesions rendering said patient at risk of a gastric cancer condition) (abstract background lines 1-3; abstract aim lines 1-3; abstract materials and methods lines 1-6; abstract results lines 1-9; pg. 597 column 1 2nd full paragraph lines 1-8; pg. 597 column 1 3rd full paragraph lines 1-13; pg. 598 column 1 1st full paragraph lines 1-14; pg. 598 paragraph bridging column 1 & 2 lines 8-22; pg. 600 column 1 1st full paragraph lines 1-5; pg. 600 column 2 2nd full paragraph lines 1-4; pg. 601 column 1 1st full paragraph lines 1-11; pg. 601 column 2 1st full paragraph lines 1-6; pg. 602 column 2 1st full paragraph lines 1-11; Table 3). Capelle also teaches patients completed upper gastrointestinal endoscopy and histological assessment of biopsies for further testing for risk for intestinal metaplasia (conducting further medical testing for gastric cancer comprising optical gastroscopic examination and biopsies for histological examination) (pg. 597 column 2 2nd full paragraph lines 1-15; pg. 597-598 paragraphs bridging pg. 597 & 598 lines 1-21).
Capelle does not teach determining the level of at least three biomarkers comprises IL-17 and another biomarker selected from lines 9-21 of claim 1.
Severin teaches a method for diagnosing cancer, in which the cancer comprises gastric cancer, through the expression levels of target analytes in the patient sample comprising measuring the expression level of at least one cytokine comprising IL-17 and TNF-alpha and further the expression level of at least one adipocytokine comprising leptin (LEP) in which the method comprises measuring the levels of at least two different target analytes (determining the levels of at two or more biomarkers (at least three) comprising IL-17 and TNF-alpha selected from a. in amended claim 1) (paragraph [0019] lines 1-4; paragraph [0066] lines 1-12; paragraph [0067] lines 1-2; paragraph [0068] lines 1-4; paragraph [0074] lines 1-4; paragraph [0075] lines 1-2; paragraph [0080] lines 1-3). Severin also teaches that this method can be used to identify relevant biomarkers which is beneficial in developing diagnostic assays and effective treatment plans to minimize patients disease risk (paragraph [0002] lines 1-6; paragraph [0003] lines 1-7; paragraph [0004] lines 1-6).
Capelle and Severin are considered to be analogous to the claimed invention because they are all in the same field of measuring levels of biomarkers in samples at risk of gastric cancer. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of identifying patients at high risk for gastric cancer through serum markers for gastric precursor lesions comprising measuring the levels of at least three biomarkers comprising leptin (LEP), pepsinogen I and II, and gastrin markers (determining the level of at least three biomarkers comprising LEP) in Capelle to incorporate measuring the level of IL-17 and TNF-alpha as taught in Severin because Severin teaches that doing so would provide a method useful to identify relevant biomarkers which is beneficial in developing diagnostic assays and effective treatment plans to minimize patients disease risk.
Regarding amended claim 2, Severin teaches measuring the expression of at least one (one or more) cytokine comprising measuring the expression of IL-8 (determining the level of one or more additional biomarker selected amongst IL-8 protein) (paragraph [0074] lines 1-4).
Regarding amended claim 4, Severin teaches measuring the expression of at least one cytokine comprising measuring the expression of IL-8 and measuring the expression level of one or more signal transduction molecules comprising measuring the expression of EGFR and STAT3 (determining the level of three additional biomarkers selected amongst IL-8 protein, EFGR, and STAT3) (paragraph [0044] lines 1-5 & 16; paragraph [0069] lines 1-5; paragraph [0074] lines 1-4).
Regarding claim 17, Capelle teaches the levels of the serum markers are measured using an enzyme immunoassay (levels of biomarkers are determined by ELISA testing) (pg. 598 column 1 1st full paragraph lines 1-14).
Regarding amended claim 22, Capelle teaches a method to identify patients at high risk for gastric cancer through serum markers for gastric precursor lesions (determining whether a human patient has lesion rendering said patient at risk of a gastric cancer condition) comprising obtaining serum (blood) samples from patients susceptible to evolve into a gastric cancer condition and measuring the level of leptin (LEP), pepsinogen I and II, and gastrin markers (determining the level of at least three biomarkers comprising LEP in a biological sample from a human patient susceptible of suffering of condition(s) to evolve in a gastric cancer condition) (abstract background lines 1-3; abstract aim lines 1-3; abstract materials and methods lines 1-6; abstract results lines 1-9; pg. 597 column 1 2nd full paragraph lines 1-8; pg. 597 column 1 3rd full paragraph lines 1-13; pg. 598 column 1 1st full paragraph lines 1-14; pg. 598 paragraph bridging column 1 & 2 lines 8-22; pg. 600 column 1 1st full paragraph lines 1-5; pg. 600 column 2 2nd full paragraph lines 1-4; pg. 601 column 1 1st full paragraph lines 1-11; pg. 601 column 2 1st full paragraph lines 1-6; pg. 602 column 2 1st full paragraph lines 1-11; Table 3). Capelle also teaches patients completed upper gastrointestinal endoscopy and histological assessment of biopsies for further testing for risk for intestinal metaplasia (conducting further medical testing for gastric cancer comprising optical gastroscopic examination and biopsies for histological examination) (pg. 597 column 2 2nd full paragraph lines 1-15; pg. 597-598 paragraphs bridging pg. 597 & 598 lines 1-21).
Capelle does not teach determining the level of at least three biomarkers comprises IL-17 and another biomarker selected from list.
Severin teaches a method for diagnosing cancer, in which the cancer comprises gastric cancer, through the expression levels of target analytes in the patient sample comprising measuring the expression level of at least one cytokine comprising IL-17 and TNF-alpha and further the expression level of at least one adipocytokine comprising leptin (LEP) in which the method comprises measuring the levels of at least two different target analytes (determining the levels of at two or more biomarkers (at least three) comprising IL-17 and TNF-alpha selected from a. in amended claim 1) (paragraph [0019] lines 1-4; paragraph [0066] lines 1-12; paragraph [0067] lines 1-2; paragraph [0068] lines 1-4; paragraph [0074] lines 1-4; paragraph [0075] lines 1-2; paragraph [0080] lines 1-3). Severin also teaches that this method can be used to identify relevant biomarkers which is beneficial in developing diagnostic assays and effective treatment plans to minimize patients disease risk (paragraph [0002] lines 1-6; paragraph [0003] lines 1-7; paragraph [0004] lines 1-6).
Capelle and Severin are considered to be analogous to the claimed invention because they are all in the same field of measuring levels of biomarkers in samples at risk of gastric cancer. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of identifying patients at high risk for gastric cancer through serum markers for gastric precursor lesions comprising measuring the levels of at least three biomarkers comprising leptin (LEP), pepsinogen I and II, and gastrin markers (determining the level of at least three biomarkers comprising LEP) in Capelle to incorporate measuring the level of IL-17 and TNF-alpha as taught in Severin because Severin teaches that doing so would provide a method useful to identify relevant biomarkers which is beneficial in developing diagnostic assays and effective treatment plans to minimize patients disease risk.
Claim(s) 3 & 5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Capelle (Capelle et al.; Heliobacter, Vol. 14, pages 596-604, November 2009), as cited on the IDS dated 01/13/2026, and Severin (WO 2015/003945 A1, January 2015) as applied to claims 1, 2, 4, 17, & 22 above, and further in view of Sun (Sun et al.; OncoTarget, Vol. 8, pages 70271-70280, August 2017).
The teachings of Capelle and Severin with respect to claim 1 is discussed above.
Regarding amended claims 3 & 5, Severin teaches measuring the expression of at least one cytokine comprising measuring the expression of IL-8 and measuring the expression level of one or more signal transduction molecules comprising measuring the expression of EGFR and STAT3 (determining the level of three additional biomarkers selected amongst IL-8 protein, EFGR, and STAT3) (paragraph [0044] lines 1-5 & 16; paragraph [0069] lines 1-5; paragraph [0074] lines 1-4).
Capelle and Severin does not teach determining the expression level of two additional biomarkers selected from a list and at least one further biomarker selected amongst EGFR and STAT3 (see claim 3) or determining the level of at least six additional biomarkers selected from a list (see claim 5).
Sun teaches a method for assessing biomarkers for diagnosis and treatment of gastric cancer comprising determining the level of biomarkers in gastric cancer samples with the Affymetrix Human Genome U133 Plus 2.0 Array in which the array determines levels of biomarkers IGFALS, KRT19, CA2, IL-8, EGFR, and STAT3 (determining expression level of two additional biomarkers of IL-8 and IGFALS and at least one further biomarker of EFGR and determining the level of at least six additional biomarkers selected from IGFALS, KRT19, CA2, IL-8, EFGR, and STAT3) (abstract lines 1-22; pg. 70277 & 70278 paragraph bridging pg. 70277 & 70278 lines 1-9). Sun also teaches that this method enables determining biomarkers for diagnosis and for guiding treatment plans and medicine of gastric cancer patients (abstract lines 21-22).
Capelle, Severin, and Sun are considered to be analogous to the claimed invention because they are all in the same field of measuring levels of biomarkers in samples at risk of gastric cancer. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of identifying patients at high risk for gastric cancer through serum markers for gastric precursor lesions comprising measuring the levels of at least three biomarkers in Capelle to incorporate measuring additional gastric cancer biomarkers as taught in Sun because Sun teaches that doing so would enable determining biomarkers for diagnosis and for guiding treatment plans and medicine of gastric cancer patients.
Claim(s) 14 & 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Capelle (Capelle et al.; Heliobacter, Vol. 14, pages 596-604, November 2009), as cited on the IDS dated 01/13/2026, and Severin (WO 2015/003945 A1, January 2015) as applied to claims 1, 2, 4, 17, & 22 above, and further in view of Tu (Tu et al.; International Journal of Cancer, Vol. 136, pages 425-434, June 2014).
The teachings of Capelle and Severin with respect to claim 1 is discussed above.
Regarding amended claim 14, Capelle and Severin does not teach repeating the method of measuring at least two biomarkers at least once over time.
Tu teaches a method to measure multiple serological markers (at least three biomarkers) multiple times over a time period to measure temporal changes in the serological markers to asses risk for progression of gastric precancerous lesions (measuring at least three biomarkers at least once over time) (abstract lines 1-14; pg. 426 paragraph bridging column 1 & 2 lines 1-27). In addition, Tu teaches that measuring temporal changes in serological markers may be useful for assessing and managing risk for progression of gastric precancerous lesions (abstract lines 1-14).
Capelle, Severin, and Tu are considered to be analogous to the claimed invention because they are all in the same field of measuring levels of biomarkers in samples at risk of gastric cancer. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of identifying patients at high risk for gastric cancer through serum markers for gastric precursor lesions comprising measuring the levels of at least three biomarkers comprising leptin (LEP), pepsinogen I and II, and gastrin markers (determining the level of at least three biomarkers comprising LEP) in Capelle to incorporate repeating this measurement to identify temporal changes in the levels of the markers as taught in Tu because Tu teaches that doing so would be useful for assessing and managing risk for progression of gastric precancerous lesions.
Regarding claim 17, Capelle teaches the levels of the serum markers are measured using an enzyme immunoassay (levels of biomarkers are determined by ELISA testing) (pg. 598 column 1 1st full paragraph lines 1-14).
Tu measuring serological biomarkers from the patient’s blood sample using an enzyme-linked immunosorbent assay (ELISA) (pg. 426 column 21sat full paragraph lines 1-9).
Claim(s) 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Capelle (Capelle et al.; Heliobacter, Vol. 14, pages 596-604, November 2009), as cited on the IDS dated 01/13/2026, and Severin (WO 2015/003945 A1, January 2015) as applied to claims 1, 2, 4, 17, & 22 above, and further in view of Pandya (Pandya, Patel, Agravat, & Singh; Journal of Clinical and Diagnostic Research, Vol. 8, pages 12-15, June 2014).
The teachings of Capelle and Severin with respect to claim 1 are discussed above.
Regarding amended claim 15, Capelle teaches measuring the level of leptin (LEP), pepsinogen I and II, and gastrin markers and also measuring H. pylori antibodies in an enzyme immunoassay to detect H. pylori infection (simultaneous or parallel step of detecting Helicobacter pylori infection through detection of the presence of specific H. pylori IgG antibodies in a biological sample) (pg. 597 column 1 1st full paragraph lines 21-23; pg. 598 column 1 1st full paragraph lines 1-14).
Capelle and Severin does not teach detection of the presence of specific H. pylori comprising IgA antibodies.
Pandya teaches detection of H. pylori infection through the use of and ELISA-A and ELISA-G kit detecting both H. pylori IgG and IgA antibodies in gastrointestinal samples (abstract context lines 1-3; abstract objectives lines 1-3; abstract materials and methods lines 1-8; pg. 12 column 1 1st full paragraph lines 1-9). In addition, Pandya teaches that there is an important clinical association between H. pylori IgA and gastric cancer and that testing for both IgG and IgA antibodies in H. pylori infection improves the diagnostic value over detection of IgG antibody alone (abstract conclusion lines 1-6; pg. 12-13 paragraph bridging pg. 12 & 13 lines 1-5).
Capelle, Severin, and Pandya are considered to be analogous to the claimed invention because they are all in the same field of measuring levels of biomarkers in samples at risk of gastric cancer. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of identifying patients at high risk for gastric cancer through serum markers for gastric precursor lesions comprising measuring the levels of at least two biomarkers comprising leptin (LEP), pepsinogen I and II, and gastrin markers (determining the level of at least two biomarkers comprising LEP) and simultaneously measuring H. pylori antibodies in an enzyme immunoassay to detect H. pylori infection in Capelle to incorporate detecting both H. pylori IgG and IgA antibodies as taught in Pandya because Pandya teaches that doing so would improves the diagnostic value over detection of IgG antibody alone in detecting H. pylori infection.
Response to Arguments
The response traverses the rejection. The response asserts that the pending claims recite determining the levels of at least three biomarkers selected from ARG1, LEP, IL-17, TNF-alpha, SELE, and MSLN biomarkers and that the cited references do not teach or suggest these particular combination of markers or that the combination could result in high levels of sensitivity or specificity. This argument has been thoroughly reviewed but was not found persuasive. First, as discussed further above, Capelle teaches a method for to identify patients at high risk for gastric cancer through serum markers for gastric precursor lesions through measuring the level of leptin (LEP), pepsinogen I and II, and gastrin markers (determining the level of at least three biomarkers comprising LEP) and analyzing to determine the predictive power of the markers in which significantly different levels of leptin (LEP) and pepsinogen I and II indicated intestinal metaplasia (abstract background lines 1-3; abstract aim lines 1-3; abstract materials and methods lines 1-6; abstract results lines 1-9; pg. 597 column 1 2nd full paragraph lines 1-8; pg. 597 column 1 3rd full paragraph lines 1-13; pg. 598 column 1 1st full paragraph lines 1-14; pg. 598 paragraph bridging column 1 & 2 lines 8-22; pg. 600 column 1 1st full paragraph lines 1-5; pg. 600 column 2 2nd full paragraph lines 1-4; pg. 601 column 1 1st full paragraph lines 1-11; pg. 601 column 2 1st full paragraph lines 1-6; pg. 602 column 2 1st full paragraph lines 1-11; Table 3). Further, Severin teaches a method for diagnosing cancer, in which the cancer comprises gastric cancer, through the expression levels of target analytes in the patient sample comprising measuring the expression level of at least one cytokine comprising IL-17 and TNF-alpha and further the expression level of at least one adipocytokine comprising leptin (LEP) in which the method comprises measuring the levels of at least two different target analytes (determining the levels of at two or more biomarkers (at least three) comprising IL-17 and TNF-alpha) (paragraph [0019] lines 1-4; paragraph [0066] lines 1-12; paragraph [0067] lines 1-2; paragraph [0068] lines 1-4; paragraph [0074] lines 1-4; paragraph [0075] lines 1-2; paragraph [0080] lines 1-3). Severin also teaches that this method can be used to identify relevant biomarkers which is beneficial in developing diagnostic assays and effective treatment plans to minimize patients disease risk (paragraph [0002] lines 1-6; paragraph [0003] lines 1-7; paragraph [0004] lines 1-6). Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of identifying patients at high risk for gastric cancer through serum markers for gastric precursor lesions comprising measuring the levels of at least three biomarkers comprising leptin (LEP), pepsinogen I and II, and gastrin markers (determining the level of at least three biomarkers comprising LEP) in Capelle to incorporate measuring the level of IL-17 and TNF-alpha as taught in Severin because Severin teaches that doing so would provide a method useful to identify relevant biomarkers which is beneficial in developing diagnostic assays and effective treatment plans to minimize patients disease risk. Therefore, the combination of Capelle and Severin teaches a combination of markers as recited in claim 1 as currently amended. Second, in response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., the combination could result in high levels of sensitivity or specificity) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
The response also asserts that Capelle found out that leptin level can be used as a biomarker and concluded that the value of measuring leptin was “rather limited” and thus Capelle does not teach or suggest the particular claimed combination of markers or that the combination could result in the demonstrated high levels of sensitivity and specificity. This argument has been thoroughly reviewed but was not found persuasive as Capelle teaches that serum leptin levels are of significant additional value in predicting gastric intestinal metaplasia (gastric cancer) and the combination of Capelle and Severin teaches the claimed combination of markers for the reasons set forth above.
The response also asserts that Severin does not remedy the deficiencies of Capelle and that although gastric cancer is mentioned among a list of diseases there is no specific example for this condition disclosed in Severin and although leptin and IL-17 are mentioned in different lists, there is no incentive to combine them, nor to connect them with gastric cancer and thus Severin, alone or combined with Capelle, does not teach or suggest the particular claimed combination of markers or that the combination could result in the demonstrated high levels of sensitivity and specificity. Further, the response asserts that the prior art does not provide a motivation to combine teachings or any expectation of success. This argument has been thoroughly reviewed but was not found persuasive. First, it is not required that the limitations of a claim be taught in a preferred embodiment and Severin does teach an embodiment of measuring expression levels of particular biomarkers in a gastric cancer sample. In addition, the claim as currently amended recites “determining whether a human patient has lesions rendering the human patient at risk of a gastric cancer condition” and “screening a biological sample of blood or plasma removed from the human patient” and therefore does not require that the biological sample be a gastric cancer sample from a human patient. Further, Severin teaches the method comprises measuring the levels of at least two different target analytes (determining the levels of at two or more biomarkers (at least three) comprising IL-17 and TNF-alpha to detect two or more target analytes from different lists for disease detection) (paragraph [0080] lines 1-3). Second, the combination of Capelle and Severin teaches the claimed combination of markers for the reasons set forth above. Further, Severin teaches that the method of Severin can be used to identify relevant biomarkers which is beneficial in developing diagnostic assays and effective treatment plans to minimize patients disease risk therefore providing a motivation to combine teachings and Capelle and Severin are considered to be analogous to the claimed invention because they are all in the same field of measuring levels of biomarkers in samples at risk of gastric cancer providing a reasonable expectation of success.
The response also asserts that Tu does teach or suggest analyzing leptin or IL-17 levels and thus Tu does not teach or suggest the particular claimed combination or markers or that the combination could result in the demonstrated high levels of specificity. This argument has been thoroughly reviewed but was not found persuasive for the reasons set forth above.
The response also asserts that Pandya relates to detecting H. pylori infection and not gastric cancer and thus Pandya does not teach or suggest the particular claimed combination of markers or that the combination could result in the demonstrated high levels of sensitivity and specificity. This argument has been thoroughly reviewed but was not found persuasive for the reasons set forth above.
For these reasons, and the reasons already made of record and modified to address the claims as currently amended, the rejections are maintained and applied to the newly amended claims.
Conclusion
Claims 1-5, 14, 15, 17, & 22 are rejected.
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 BAILEY C BUCHANAN whose telephone number is (703)756-1315. The examiner can normally be reached Monday-Friday 8:00am-5:00pm ET.
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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 the organization where this application or proceeding is assigned is 571-273-8300.
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/BAILEY BUCHANAN/Examiner, Art Unit 1682
/JEHANNE S SITTON/Primary Examiner, Art Unit 1682
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