DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
2. Applicant’s election without traverse of Group I (claims 1-23 and 35-40 with species (tumour marker antigens): a. p53, synovial sarcoma, X breakpoint (SSX1) and p62 also elected without traverse in the reply filed on March 3, 2026 is acknowledged.
3. Claims 1-42 are pending.
Claims 3, 18, 24-34, 41 and 42, drawn to non-elected inventions and non-elected species are withdrawn from the merits.
Claim 43 has been cancelled.
Claims 4-5, 8-10, 15, 17-21, 23, 27, 29-31, 33-36, 38, 39 and 41 have been amended.
Claims 1, 2, 4-17, 19-23 and 35-40 are examined on the merits with species, (tumour marker antigens): a. p53, synovial sarcoma, X breakpoint (SSX1) and p62.
Claim Rejections - 35 USC § 112
4. The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
5. Claims 14, 16 and 20-22 are 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.
a. Claim 14 reads on predicting response to a lung cancer treatment, wherein a complex of specifically bound autoantibodies/tumor marker antigens is determined to be present or not and compared to specific binding between tumour marker antigens and the autoantibodies with a previously established relationship, wherein a change in the binding, when compared to controls predicts the patient’s likely outcome of treatment and whether or not the patient will be responsive to the treatment. It is not clear what are the controls. It is not clear if it the “previously established relationship” is regarded as the control and/or is it before lung cancer treatment commenced. It is not clear what is a previously established relationship and the components of the relationship. It is not clear when the lung cancer treatment commenced. Accordingly, the metes and bounds cannot be determined.
b. Claims 16 and 20-22 recite “use of” claim, wherein it seems the claims read on a process. However, the claims are vague and indefinite in that it does not set forth any steps for one of ordinary skill in the art to follow or state to implement the process.
6. Claim 20 recites the limitation "the use" spanning lines 1 and 2. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 101
7. 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.
8. Claims 16 and 20-22 are rejected under 35 U.S.C. 101 is not patent eligible subject matter because the claim is directed to a process, however do not recite any method steps to implement the process. Therefore, it does not fall within at least one of the four categories of patent eligible subject matter recited in 35 U.S.C. 101 (process, machine, manufacture, or composition of matter), because they are not presented in the format of a proper process claim. See MPEP 2173.05(q).
9. The claimed invention (claims 1, 2, 4-12, 14, 16, 17, 19-23 and 35-40) is directed to non-statutory subject matter. The claim(s) 8 does/do not fall within at least one of the four categories of patent eligible subject matter because they read on a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract) without significantly more.
The claimed invention (claims 1, 2, 4-12, 14, 16, 17, 19-23 and 35-40) is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract) without significantly more. The claim(s) recite(s) method for detecting lung cancer determining the presence or absence of complexes between a tumour marker antigen bound to autoantibodies present in the test sample and methods of predicting response to a lung cancer treatment comprising detecting the presence or absence of complexes between a tumour marker antigen(s) and/or panel of tumour marker antigens bound to autoantibodies present in the test sample, comparing the amount of specific binding between the tumour marker antigens and the autoantibodies with a previously established relationship between the amount of binding and like outcome of treatment, wherein a change in the amount of specific binding when compared to controls predicts the patient will or will not respond to the treatment.
These methods also include a tumor marker antigen that is a naturally occurring protein or polypeptide.
The judicial exception is not integrated into a practical application because a biological sample from a patient and a healthy reference standard required to use the correlation does not add a meaningful limitation to the method as they are insignificant extra-solution activity. Moreover, the test sample containing an autoantibody bound to an antigen or complex detected or found present and indicative of lung cancer is not integrated into a practical application. The claim(s) do/does not include additional elements that are sufficient to amount to significantly more than the judicial exception because it does not recite something significantly different than a judicial exception. The rationale for this determination is explained below:
The analysis as set forth in the 2019 Guidance is as follows:
Step 1: Yes, claims are drawn to a method which is one of the four statutory categories, a process. The claims also read on a naturally occurring protein or polypeptide that is not markedly different in structure than the naturally occurring tumour marker antigen.
Step 2A, prong 1: Yes, the claims recite/describe/set forth a judicial exception. The claim describes the relationship between the presence of autoantibodies specifically bound to tumour marker antigens and these resulting complexes present in the test sample is indicative of the subject having lung cancer. Furthermore, the claims describe the relationship between the presence of autoantibodies specifically bound to tumour marker antigens and these resulting complexes compared with a previously established relationship between the amount of binding and the likely outcome or response of/to lung cancer treatment, wherein a change in the amount of specific binding when compared to controls is predictive of said outcome or response.
Step 2A, prong 2: No, the judicial exception is not integrated into a practical application. The claims do not rely on or use the exception here. Once the complexes are detected the diagnosis is rendered and the specific binding between the tumour marker antigens and autoantibodies resulting in said complexes is compared to a previously established relationship and controls predicts response to lung cancer treatment. There are no additional elements or combination of additional elements to apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception.
Step 2B: There is no inventive concept present in the clams. The steps of analyzing the presence or level of an autoantibodies in a test sample bound to a panel of tumour marker antigens and presence of resulting complexes is established by well understood, routine conventional methods, and in addition they are pre-solution activity, i.e. data gathering necessary to perform the correlation. The following claims and steps inform one of ordinary skilled in the art, the presence of the complexes and their presence compared to a previously established relationship and/or controls is indicative of lung cancer within the subject and/or outcome of lung cancer treatment and response to said treatment. The claims do not recite additional elements that amount to significantly more than the judicial exception. Accordingly, these claims are not be eligible under step 2A or step 2B.
Claims 1, 2, 4-12, 14, 16, 17, 19-23 and 35-40 are drawn to a non-statutory method having a "natural principle" as a limiting element or step without reciting additional elements/steps that integrate the natural principle into the claimed invention such that the natural principle is practically applied, and are sufficient to ensure that the claim amounts to significantly more than the natural principle itself. In the instant case, the "natural principle" is: detecting an autoantibody/tumor marker antigen complex is indicative of lung cancer, as well as the detection of said complex compared to a previously established relationship and/or a control is indicative of the lung cancer’s response to lung cancer treatment or likely outcome of the treatment. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because assaying for candidate cancer biomarkers does not add significantly more and is not an inventive concept. Because methods for making such determinations were well known in the art, these steps simply tell researchers to engage in well-understood, routine, conventional activity previously engaged in by scientists in the field. Such activities are normally not sufficient to transform an unpatentable law of nature into a patent-eligible application of such law. Detection of autoantibodies bound to tumour marker antigen biomarkers has been observed by applicant but not engineered by applicant. The claims do not add significantly more to the natural phenomenon because the claims do not require a novel reagent, novel apparatus or incorporate a novel treatment based on the correlation.
A claim that focuses on use of a natural principle must also include additional elements or steps to show that the inventor has practically applied, and added something significant to, the natural principle itself. See Mayo, 101 USPQ2d at 1966. A recited element such as “detecting”, “contacting”, “plotting”, “calculating”, “diagnosing”, “comparing” and “determining” based on the natural principle imposes no meaningful limit on the performance of the claimed invention. As set forth the claims do not impose meaningful limits on the performance of the claimed invention. Patents cannot be obtained on subject matter identified by the courts as being exempted from eligibility (i.e., laws of nature, natural phenomenon, and abstract ideas). Further, the active method steps are conventional and routine in the art for the reasons stated above and the claims do not amount to significantly more than the recited natural principle. The claims do not "practically apply" the natural principle; rather, the claims "simply inform" the natural principle to one performing routine active method steps and do not amount to significantly more than the natural principle itself. Thus, the technology used by the instant claims is well-known in the art and does not contribute significantly more to the judicial exception. See the 2019 Revised Patent Subject Matter Eligibility Guidance and Federal Register https://www.federalregister.gov/documents/2019/10/18/2019-22782/october-2019-patent-eligibility-guidance-update; and FDsys.gov.
Claim Rejections - 35 USC § 102
9. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
10. Claim(s) 1, 2, 4-12, 14, 16, 17, 19-23 and 35-40 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Murray et al., US 2017/0138951 (published May 18, 2017/ IDS reference #1 submitted July 1, 2025). Murray discloses assays for detecting lung cancer utilizing “…a method of detecting an antibody in a test sample comprising a bodily fluid from a mammalian subject, the method comprising the steps of:
(a) contacting said test sample with a plurality of different amounts of an antigen specific for said antibody; (b) detecting the amount of specific binding between said antibody and said antigen;
(c) plotting or calculating a curve of the amount of said specific binding versus the amount of antigen for each amount of antigen used in step (a);
(d) calculating a secondary curve parameter from the curve plotted or calculated in step (c); and (e) determining the presence or absence of said antibody based upon a combination of:
(i) the amount of specific binding between said antibody and said antigen determined in step (b); and (ii) said secondary curve parameter determined in step (d).”, see page 2, sections 0009-0012.
Moreover, “…a method of detecting two or more antibodies in a test sample comprising a bodily fluid from a mammalian subject, the method comprising the steps of:
(a) contacting said test sample with a panel comprising two or more sets of antigens, wherein each of said antigens in said panel is specific for at least one of said two or more antibodies; (b) detecting complexes of said antigens bound to antibodies present in said test sample; (c) for each antigen plotting or calculating a separate curve of the amount of said specific binding versus the amount of antigen for each amount of antigen used in step (a); (d) calculating a secondary curve parameter for each curve plotted or calculated in step (c); and (e) determining the presence or absence of said two or more antibodies based upon a combination of:
(i) the amount of specific binding between said antibody and said antigen determined in step (b); and (ii) said secondary curve parameter determined in step (d), for each of the curves plotted or calculated in step (c).”, see page 2, sections 0013-0015; and page 3, sections 0031-0033.
The methods can be used to build up a profile of autoantibody production in a patient can be provided implementing in vitro immunoassays, see page 8, section 0093; and page 9, section 0098.
The array or panel implemented in the disclosed method may comprise multiple different amounts of antigen, as well as “…one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty or more sets of antigens.”, see page 6, section 0071; page 7, section 0078; and page 9, sections 0098, 0103 and 0104.
Samples tested for the presence of the autoantibodies using the method of the invention include “…plasma, serum, whole blood, urine, sweat, lymph, faeces, cerebrospinal fluid, ascites, pleural effusion, seminal fluid, sputum, nipple aspirate, post-operative seroma, saliva, amniotic fluid, tears or wound drainage fluid.”, see page 7, section 0080.
The disclosed method can detect/measure autoantibodies to p53, SSX1 and p62, see sections 0116 and 0117 spanning pages 10 and 11; and Table 11 on page 23. Additional tumour marker antigens can be detected utilizing the disclosed method, see page 6, section 0071; page 7, section 0078; and page 9, sections 0098, 0103 and 0104. These tumour marker antigens comprise HuD, MAGE A4, SOX2, NY-ESO-1, CAGE, CK20, p53-95, CK8, Kras G13/Q61H, Lmyc2, alpha enolase (is the same as a-enolase-1), see page 2, section 0021; sections 0023-0027 bridging pages 3 and 4; section 0117 spanning pages 10 and 11; page 13, section 0139; Table 1 on page 15; section 0164 and Table 4 on page 16; and Table 9 on page 22.
“In one embodiment, the presence or absence of antibody is determined by comparison of both the amount of specific binding between the antibody and the antigen and the secondary curve parameter with pre-determined cut-off values. Here, a curve of the amount of specific binding versus the amount of antigen for each amount of antigen used in the titration series is plotted, and the level of binding in known positive samples (e.g. a populations of patients with disease) are compared with the level of binding observed in known negative samples (e.g. normal individuals) in case-controlled studies. Cut-off values for antibody binding at one or more points on the titration curve are chosen that maximise sensitivity (few false negatives) while maintaining high specificity (few false positives). Provided the curve of the amount of specific binding versus the amount of antigen for each amount of antigen used in the titration series is a dose response curve, a measurement is considered to be positive if the amount of specific binding determined for one or more points on the titration curve is above the cut-off point determined.”, see page 4, sections 0038 and 0039; section 0106 bridging pages 9 and 10; and section 0139 bridging pages 13 and 14.
“Following detection of the amount of antigen/antibody binding at each amount of antigen used in the titration series, and the plotting of a curve of the amount of specific binding versus the amount of antigen for each amount of antigen used in the titration series, a secondary curve parameter is calculated. The secondary curve parameter may be calculated from either a linear or logarithmic regression curve. Herein a secondary curve parameter is any calculated value which provides an indication of the nature of the curve…These secondary curve parameters are illustrated in FIG. 1.”, see page 2, sections 0010 and 0013; page 0031, section 0031; page 4, section 0041; page 6, sections 0065-0067; page 9, section 0095-0097; page 10, section 0112-0114.
“[T]he immunoassays are used in predicting the response of a cancer patient to anti-cancer treatment (e.g. surgical resection, vaccination, anti-growth factor or signal transduction therapies, radiotherapy, endocrine therapy, human antibody therapy, chemotherapy), the presence of an elevated level of autoantibodies or an altered secondary curve parameter showing the required directionality, as compared to “normal” control individuals, may be taken as an indication of whether or not the individual is likely to respond to the anti-cancer treatment. The “normal” control individuals will preferably be age-matched controls not having any diagnosis of cancer based on clinical, imaging and/or biochemical criteria. A relationship between the level of autoantibodies or the secondary curve parameter, compared to controls, and likely success of treatment can be established by observation of the outcome of such treatment in patients whose autoantibody status and secondary curve parameter is monitored throughout treatment. The previously established relationship may then be used to predict the likelihood of success for each treatment in a given patient based on assessment of autoantibody status and secondary curve parameter.”, see section 0121 bridging pages 11 and 12.
Claim Rejections - 35 USC § 103
12. 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.
13. Claim(s) 1, 2, 4-17, 19-23 and 35-40 is/are rejected under 35 U.S.C. 103 as being unpatentable over Murray et al., US 2017/0138951 (published May 18, 2017/ IDS reference #1 submitted July 1, 2025). Murray teaches assays for detecting lung cancer utilizing “…a method of detecting an antibody in a test sample comprising a bodily fluid from a mammalian subject, the method comprising the steps of:
(a) contacting said test sample with a plurality of different amounts of an antigen specific for said antibody; (b) detecting the amount of specific binding between said antibody and said antigen;
(c) plotting or calculating a curve of the amount of said specific binding versus the amount of antigen for each amount of antigen used in step (a);
(d) calculating a secondary curve parameter from the curve plotted or calculated in step (c); and (e) determining the presence or absence of said antibody based upon a combination of:
(i) the amount of specific binding between said antibody and said antigen determined in step (b); and (ii) said secondary curve parameter determined in step (d).”, see page 2, sections 0009-0012.
Moreover, “…a method of detecting two or more antibodies in a test sample comprising a bodily fluid from a mammalian subject, the method comprising the steps of:
(a) contacting said test sample with a panel comprising two or more sets of antigens, wherein each of said antigens in said panel is specific for at least one of said two or more antibodies; (b) detecting complexes of said antigens bound to antibodies present in said test sample; (c) for each antigen plotting or calculating a separate curve of the amount of said specific binding versus the amount of antigen for each amount of antigen used in step (a); (d) calculating a secondary curve parameter for each curve plotted or calculated in step (c); and (e) determining the presence or absence of said two or more antibodies based upon a combination of:
(i) the amount of specific binding between said antibody and said antigen determined in step (b); and (ii) said secondary curve parameter determined in step (d), for each of the curves plotted or calculated in step (c).”, see page 2, sections 0013-0015; and page 3, sections 0031-0033.
The methods can be used to build up a profile of autoantibody production in a patient can be provided implementing in vitro immunoassays, see page 8, section 0093; and page 9, section 0098.
The array or panel implemented in the taught method may comprise multiple different amounts of antigen, as well as “…one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty or more sets of antigens.”, see page 6, section 0071; page 7, section 0078; and page 9, sections 0098, 0103 and 0104.
Samples tested for the presence of the autoantibodies using the method of the invention include “…plasma, serum, whole blood, urine, sweat, lymph, faeces, cerebrospinal fluid, ascites, pleural effusion, seminal fluid, sputum, nipple aspirate, post-operative seroma, saliva, amniotic fluid, tears or wound drainage fluid.”, see page 7, section 0080.
The taught method can detect/measure autoantibodies to p53, SSX1 and p62, see sections 0116 and 0117 spanning pages 10 and 11; and Table 11 on page 23. Additional tumour marker antigens can be detected utilizing the disclosed method, see page 6, section 0071; page 7, section 0078; and page 9, sections 0098, 0103 and 0104. These tumour marker antigens comprise HuD, MAGE A4, SOX2, NY-ESO-1, CAGE, CK20, p53-95, CK8, Kras G13/Q61H, Lmyc2, alpha enolase (is the same as a-enolase-1), see page 2, section 0021; sections 0023-0027 bridging pages 3 and 4; section 0117 spanning pages 10 and 11; page 13, section 0139; Table 1 on page 15; section 0164 and Table 4 on page 16; and Table 9 on page 22.
“In one embodiment, the presence or absence of antibody is determined by comparison of both the amount of specific binding between the antibody and the antigen and the secondary curve parameter with pre-determined cut-off values. Here, a curve of the amount of specific binding versus the amount of antigen for each amount of antigen used in the titration series is plotted, and the level of binding in known positive samples (e.g. a populations of patients with disease) are compared with the level of binding observed in known negative samples (e.g. normal individuals) in case-controlled studies. Cut-off values for antibody binding at one or more points on the titration curve are chosen that maximise sensitivity (few false negatives) while maintaining high specificity (few false positives). Provided the curve of the amount of specific binding versus the amount of antigen for each amount of antigen used in the titration series is a dose response curve, a measurement is considered to be positive if the amount of specific binding determined for one or more points on the titration curve is above the cut-off point determined.”, see page 4, sections 0038 and 0039; section 0106 bridging pages 9 and 10; and section 0139 bridging pages 13 and 14.
“Following detection of the amount of antigen/antibody binding at each amount of antigen used in the titration series, and the plotting of a curve of the amount of specific binding versus the amount of antigen for each amount of antigen used in the titration series, a secondary curve parameter is calculated. The secondary curve parameter may be calculated from either a linear or logarithmic regression curve. Herein a secondary curve parameter is any calculated value which provides an indication of the nature of the curve…These secondary curve parameters are illustrated in FIG. 1.”, see page 2, sections 0010 and 0013; page 0031, section 0031; page 4, section 0041; page 6, sections 0065-0067; page 9, section 0095-0097; page 10, section 0112-0114.
“[T]he immunoassays are used in predicting the response of a cancer patient to anti-cancer treatment (e.g. surgical resection, vaccination, anti-growth factor or signal transduction therapies, radiotherapy, endocrine therapy, human antibody therapy, chemotherapy), the presence of an elevated level of autoantibodies or an altered secondary curve parameter showing the required directionality, as compared to “normal” control individuals, may be taken as an indication of whether or not the individual is likely to respond to the anti-cancer treatment. The “normal” control individuals will preferably be age-matched controls not having any diagnosis of cancer based on clinical, imaging and/or biochemical criteria. A relationship between the level of autoantibodies or the secondary curve parameter, compared to controls, and likely success of treatment can be established by observation of the outcome of such treatment in patients whose autoantibody status and secondary curve parameter is monitored throughout treatment. The previously established relationship may then be used to predict the likelihood of success for each treatment in a given patient based on assessment of autoantibody status and secondary curve parameter.”, see section 0121 bridging pages 11 and 12.
Murray does not teach administering a lung cancer treatment to the diagnosed subject.
However, Murray does teach anti-cancer treatments that are categorized as effective or not, predictive of response or not based on the presence or absence of specific binding between the patient’s autoantibodies and tumour marker proteins in the panel or array, see sections 0118 and 0121 on page 11; and page 12, sections 0125 and 0126. These anti-cancer treatments are “…surgical resection, vaccination, anti-growth factor or signal transduction therapies, radiotherapy, endocrine therapy, human antibody therapy, chemotherapy”, see page 11, sections 0118, 0121; and page 12, sections 0125 and 0126.
It would have been obvious to one of ordinary skill in the art before
the effective filing date of the claimed invention to combine the teachings
within the reference to treat the diagnosed lung patients with the lung anti-cancer treatment(s) that are known to be given to an individual with this particular type of cancer. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success by these teachings in the reference, that these treatments are administered once positively diagnosed with lung cancer given Murray teaches assessments of these treatments and information that yields evidence regarding cancer prognosis, progression, monitoring of cancer and efficacy of treatment(s), see Murray in its entirety.
Conclusion
14. Any inquiry concerning this communication or earlier communications from the Examiner should be directed to ALANA HARRIS DENT whose telephone number is (571)272-0831. The Examiner works a flexible schedule, however she can generally be reached 8AM-8PM, Monday through Friday.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Julie Wu can be reached on 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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ALANA HARRIS DENT
Primary Examiner
Art Unit 1643
13 April 2026
/Alana Harris Dent/Primary Examiner, Art Unit 1643
Prosecution Insights