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 .
Election/Restrictions
Applicant’s election without traverse of group I, claims 28-41 in the reply filed on 06/30/2026 is acknowledged.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. GB 2103200.8, filed on 03/08/2021.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 28-41 are rejected under 35 U.S.C. 101 because they constitute abstract ideas and may further contain laws of nature.Regarding independent claim 28, a two-step analysis is performed:Step 1: Does the claim fall within a statutory category?
Yes, it is a method/process.
Step 2A, Prong 1: Identify the law of nature/natural phenomenon/abstract ideas.
A method of treating lung cancer in a subject, the method comprising the steps of:(a) obtaining an indication of the presence of lung cancer in a subject by a method comprising the step: determining the presence of or level of one or more biomarkers selected from the group consisting of PLD3, MAGE4A, GAGE2D, MTAP and UCHL1 polypeptides within a biological sample obtained from the subject, wherein the biological sample comprises exosomes and/or polypeptides obtained therefrom, wherein the presence of or level of one or more of the biomarkers within the biological sample is indicative of the presence of lung cancer in the subject; and (b) administering a treatment appropriate for treating lung cancer to the subject if an indication of the presence of lung cancer in the subject is obtained, thereby treating lung cancer in the subject.
Correlating the presence of a biomarker with the presence of lung cancer is considered a mental process, where it is evaluated based on one’s observation, evaluation, judgment and opinion using data as comparison, making this an abstract idea. Furthermore, the biomarkers are a naturally occurring biological compound that occur in lung cancer cells, which constitutes laws of nature.
Step 2A Prong 2: Has the abstract idea been integrated into a particular practical application?
The claim as a whole does not integrate the abstract idea into a practical application. Other than the abstract idea, claim 28 recites the additional elements: Determining the level and presence of biomarkers PLD3, MAGE4A, GAGE2D, MTAP and UCHL1, and administering a treatment if indicative of the presence of lung cancer (where “if” is non-limiting and does not need to happen in the claim). With respect to mentioned additional elements, they represent insignificant extra solution activity (e.g., mere data gathering), as well as well-understood, routine, conventional activities known to the industry, specified at a high level of generality (e.g., treating lung cancer with a unspecified treatment). Thus, there is no application of the abstract idea, much less a particular practical application.
Step 2B: Does the claim recite any elements which are significantly more than the abstract idea?
Claim 28 does not provide an inventive concept (significantly more than the abstract idea). Determining the level and presence of biomarkers PLD3, MAGE4A, GAGE2D, MTAP and UCHL1 is considered insignificant extra solution activity (e.g., mere data gathering), and administering a treatment if indicative of the presence of lung cancer is well-understood, routine, conventional activities known to the industry, specified at a high level of generality. Furthermore, the additional elements above, alone and in combination within claim 28 as a whole, are well understood, routine, and conventional activities within the prior art (see 102 and 103 rejections).
Dependent claims 29-35 do not resolve any of the issues discussed above because they involve limitations with more insignificant extra-solution activity (e.g., the type of biological sample being assayed) and/or abstract ideas in the form of mental process. The dependent claims to claim 28 are thus additionally rejected under 101.
Regarding dependent claim 29, a two-step analysis is performed:Step 1: Does the claim fall within a statutory category?
Yes, it is a method/process.
Step 2A, Prong 1: Identify the law of nature/natural phenomenon/abstract ideas.
The method as claimed in claim 28, the method comprising the steps:(a) obtaining an indication of the presence of early stage lung cancer in a subject by a method comprising the step: determining the presence of or level of one or more biomarkers selected from the group consisting of PLD3, MTAP and/or UCHL1 polypeptides within a biological sample obtained from the subject, wherein the biological sample comprises exosomes and/or polypeptides obtained therefrom, and wherein the presence of PLD3, MTAP and/or UCHL1 polypeptides within the biological sample is indicative of the presence of early stage lung cancer (preferably stages I, II, or III) in the subject; Filed Herewith and (b) administering a treatment appropriate for treating early stage lung cancer to the subject if an indication of the presence of early stage lung cancer in the subject is obtained, thereby treating early stage lung cancer in the subject.
Correlating the presence of a biomarker with the presence of early lung cancer is considered a mental process, where it is evaluated based on one’s observation, evaluation, judgment and opinion using data as comparison, making this an abstract idea. Furthermore, the biomarkers are a naturally occurring biological compound that occur in lung cancer cells, which constitutes laws of nature.
Step 2A Prong 2: Has the abstract idea been integrated into a particular practical application?
The claim as a whole does not integrate the abstract idea into a practical application. Other than the abstract idea, claim 29 recites the additional elements: Determining the level and presence of biomarkers PLD3, MTAP and UCHL1, and administering a treatment if indicative of the presence of early lung cancer (where “if” is non-limiting and does not need to happen in the claim). With respect to mentioned additional elements, they represent insignificant extra solution activity (e.g., mere data gathering), as well as well-understood, routine, conventional activities known to the industry, specified at a high level of generality (e.g., treating early lung cancer with a unspecified treatment). Thus, there is no application of the abstract idea, much less a particular practical application.
Step 2B: Does the claim recite any elements which are significantly more than the abstract idea?
Claim 29 does not provide an inventive concept (significantly more than the abstract idea). Determining the level and presence of biomarkers PLD3, MTAP and UCHL1 is considered insignificant extra solution activity (e.g., mere data gathering), and administering a treatment if indicative of the presence of early lung cancer is well-understood, routine, conventional activities known to the industry, specified at a high level of generality. Furthermore, the additional elements above, alone and in combination within claim 29 as a whole, are well understood, routine, and conventional activities within the prior art (see 102 and 103 rejections).
Regarding dependent claim 30, a two-step analysis is performed:Step 1: Does the claim fall within a statutory category?
Yes, it is a method/process.
Step 2A, Prong 1: Identify the law of nature/natural phenomenon/abstract ideas.
The method as claimed in claim 28, the method comprising the steps:(a) obtaining an indication of the presence of metastatic lung disease in a subject by a method comprising the step: determining the presence of or level of one or more biomarkers selected from the group consisting of MAGE4A and GAGE2D polypeptides within a biological sample obtained from the subject, wherein the biological sample comprises exosomes and/or polypeptides obtained therefrom, and wherein the presence of MAGE4A and/or GAGE2D polypeptides within the biological sample is indicative of the presence of metastatic lung disease in the subject; and (b) administering a treatment appropriate for treating metastatic lung disease to the subject if an indication of the presence of metastatic lung disease in the subject is obtained, thereby treating metastatic lung disease in the subject.
Correlating the presence of a biomarker with the presence of metastatic lung cancer is considered a mental process, where it is evaluated based on one’s observation, evaluation, judgment and opinion using data as comparison, making this an abstract idea. Furthermore, the biomarkers are a naturally occurring biological compound that occur in lung cancer cells, which constitutes laws of nature.
Step 2A Prong 2: Has the abstract idea been integrated into a particular practical application?
The claim as a whole does not integrate the abstract idea into a practical application. Other than the abstract idea, claim 30 recites the additional elements: Determining the level and presence of biomarkers MAGE4A and GAGE2D, and administering a treatment if indicative of the presence of metastatic lung disease (where “if” is non-limiting and does not need to happen in the claim). With respect to mentioned additional elements, they represent insignificant extra solution activity (e.g., mere data gathering), as well as well-understood, routine, conventional activities known to the industry, specified at a high level of generality (e.g., treating metastatic lung disease with an unspecified treatment). Thus, there is no application of the abstract idea, much less a particular practical application.
Step 2B: Does the claim recite any elements which are significantly more than the abstract idea?
Claim 30 does not provide an inventive concept (significantly more than the abstract idea). Determining the level and presence of biomarkers MAGE4A and GAGE2D is considered insignificant extra solution activity (e.g., mere data gathering), and administering a treatment if indicative of the presence of metastatic lung disease is well-understood, routine, conventional activities known to the industry, specified at a high level of generality. Furthermore, the additional elements above, alone and in combination within claim 30 as a whole, are well understood, routine, and conventional activities within the prior art (see 102 and 103 rejections).
Regarding independent claim 36, a two-step analysis is performed:Step 1: Does the claim fall within a statutory category?
Yes, it is a method/process.
Step 2A, Prong 1: Identify the law of nature/natural phenomenon/abstract ideas.
A method of treating lung cancer in a subject, the method comprising the steps of:(a) obtaining an indication of the presence of lung cancer in a subject by a method comprising the steps: (i) contacting a biological sample obtained from the subject with a solid support, wherein the biological sample is a sample of isolated and/or purified exosomes which have been obtained from the subject, wherein the solid support comprises a detection zone comprising one or more (e.g. 1, 2, 3, 4, or 5) immobilised specific binding partners against one or more biomarkers selected from the group consisting of PLD3, MAGE4A, GAGE2D, MTAP and UCHL1 polypeptides; and (ii) detecting the presence or absence of bound specific binding partners in the detection zone, wherein the presence of bound specific binding partners in the detection zone is indicative of the presence of lung cancer in the subject; and (b) administering a treatment appropriate for treating lung cancer to the subject if an indication of the presence of lung cancer in the subject is obtained, thereby treating lung cancer in the subject.
Correlating the presence of a biomarker with the presence of lung cancer is considered a mental process, where it is evaluated based on one’s observation, evaluation, judgment and opinion using data as comparison, making this an abstract idea. Furthermore, the biomarkers are a naturally occurring biological compound that occur in lung cancer cells, which constitutes laws of nature.
Step 2A Prong 2: Has the abstract idea been integrated into a particular practical application?
The claim as a whole does not integrate the abstract idea into a practical application. Other than the abstract idea, claim 36 recites the additional elements: Contacting a biological sample with a solid support comprising detection zones with specific binding partners against one or more biomarkers selected from the group consisting of PLD3, MAGE4A, GAGE2D, MTAP and UCHL1, and administering a treatment if indicative of the presence of early lung cancer (where “if” is non-limiting and does not need to happen in the claim). With respect to mentioned additional elements, they represent insignificant extra solution activity (e.g., mere data gathering), as well as well-understood, routine, conventional activities known to the industry, specified at a high level of generality (e.g., treating lung cancer with an unspecified treatment). Thus, there is no application of the abstract idea, much less a particular practical application.
Step 2B: Does the claim recite any elements which are significantly more than the abstract idea?
Claim 36 does not provide an inventive concept (significantly more than the abstract idea). Contacting a biological sample with a solid support comprising detection zones with specific binding partners against one or more biomarkers selected from the group consisting of PLD3, MAGE4A, GAGE2D, MTAP and UCHL1 is considered insignificant extra solution activity (e.g., mere data gathering), and administering a treatment indicative of lung cancer is well-understood, routine, conventional activities known to the industry, specified at a high level of generality. Furthermore, the additional elements above, alone and in combination within claim 36 as a whole, are well understood, routine, and conventional activities within the prior art (see 102 and 103 rejections).
Dependent claims 37-41 do not resolve any of the issues discussed above because they involve limitations with more insignificant extra-solution activity (e.g., the type of biological sample being assayed) and/or abstract ideas in the form of mental process. Claims dependent on claim 36 are thus additionally rejected under 101.
Claim Interpretation
The examiner is interpreting the use of “if” to not be limiting or required in the claim.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 28 and 31 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Beer et al. (US PG-Pub 20040063120 A1).
Regarding claim 28, Beer et al. teaches a method of treating lung cancer in a subject (see Abstract, disclosing gene biomarkers provide targets for cancer drug screens and therapeutic applications.), the method comprising the steps of:(a) obtaining an indication of the presence of lung cancer in a subject by a method comprising the step: determining the presence of or level of one or more biomarkers selected from the group consisting of PLD3, MAGE4A, GAGE2D, MTAP and UCHL1 polypeptides within a biological sample obtained from the subject, wherein the biological sample comprises exosomes and/or polypeptides obtained therefrom (see [0008], disclosing characterizing lung tissue in a subject, and detecting a decreased or increased expression of a marker relative to a non-cancerous lung tissue control, including UCHL1, AOE372, ATP5D, B4GALT, Ppase, GRP58, GSTM4, P4HB and TPI.), wherein the presence of or level of one or more of the biomarkers within the biological sample is indicative of the presence of lung cancer in the subject (see [0041], disclosing the candidate tumor markers in this study were found using quantitative assessment with 2D-PAGE gels and mass spectrometry, and a number were increased in lung adenocarcinomas as compared to normal lung tissue. Among these, UCHL1 was increased by 3.5 fold.); and (b) administering a treatment appropriate for treating lung cancer to the subject if an indication of the presence of lung cancer in the subject is obtained, thereby treating lung cancer in the subject (see [0017], disclosing providing a lung cell sample with a test compound, such as a therapeutic drug, and screening its effectiveness by observing a change in expression of a marker, such as UCHL1.).
Regarding claim 31, the examiner is interpreting the group of biomarkers to be able to consist of between one to five biomarkers, where each includes one distinct polypeptide.
Beer et al. teaches wherein the group of biomarkers consists of 1, 2, 3, 4, or 5 of PLD3, MAGE4A, GAGE2D, MTAP and UCHL1 polypeptides (see [0008], disclosing detecting a decreased or increased expression of a marker relative to a non-cancerous lung control sample, selected from the group UCHL1, AOE372, ATP5D, B4GALT, Ppase, GRP58, GSTM4, P4HB and TPI.).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 29 and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Beer et al. as applied to claim 28 above, and further in view of Borgia (US PG-Pub 20130225442 A1).
Regarding claim 29, Beer et al. fails to teach the method comprising the steps:(a) obtaining an indication of the presence of early stage lung cancer in a subject by a method comprising the step: determining the presence of or level of one or more biomarkers selected from the group consisting of PLD3, MTAP and/or UCHL1 polypeptides within a biological sample obtained from the subject, wherein the biological sample comprises exosomes and/or polypeptides obtained therefrom, and wherein the presence of PLD3, MTAP and/or UCHL1 polypeptides within the biological sample is indicative of the presence of early stage lung cancer (preferably stages I, II, or III) in the subject; and (b) administering a treatment appropriate for treating early stage lung cancer to the subject if an indication of the presence of early stage lung cancer in the subject is obtained, thereby treating early stage lung cancer in the subject.
However, in the analogous art of lung cancer test, Borgia teaches methods for diagnosing lung cancer, specifically non-small cell lung cancer (NSCLC), with an assortment of biomarkers with diagnostic or prognostic value for diagnosing a patient with lung cancer. In some aspects, it is determined whether or not a mammal has NSCLC versus non-NSCLC lung cancer, where the mammal is evaluated to have an elevated level of expression of one or more nucleic acids, or a polypeptide encoded by the nucleic acid or an autoantibody to said polypeptide, selected from a group which includes methylthioadenosine phosphorylase (MTAP). The presence or absence of an elevated level is used to determine treatment for a lung cancer such as NSCLC, especially those with early stage lung cancer such as Stage I, identified during patient prognostication (see Borgia, Abstract, [0015]-[0016], [0094]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of diagnosing lung cancer in patients of Beer et al. by incorporating obtaining the expression of MTAP in making distinctions in patients with early or stage I lung cancer versus nonmalignant diseases (as taught by Borgia), for the benefit of obtaining critical prognostic information for non-small cell lung cancer patients for guiding therapeutic decisions (see Borgia [0094]).
Regarding claim 32, Beer et al. fails to teach wherein the group of biomarkers consists of:(i) PLD3; (ii) MTAP; or (iii) PLD3 and MTAP.
However, Borgia teaches determining whether or not a mammal has NSCLC versus non-NSCLC lung cancer or benign lung diseases, where the mammal is evaluated to have an elevated level of expression of one or more nucleic acids, or a polypeptide encoded by the nucleic acid or an autoantibody to said polypeptide, selected from a group which includes methylthioadenosine phosphorylase (MTAP). The presence or absence of an elevated level is used to determine treatment for a lung cancer such as NSCLC, especially those with early stage lung cancer such as Stage I, identified during patient prognostication (see Borgia, Abstract, [0015]-[0016])
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of diagnosing lung cancer in patients of Beer et al. by incorporating obtaining the expression of MTAP as a biomarker (as taught by Borgia), for the benefit of obtaining critical prognostic information for non-small cell lung cancer patients for guiding therapeutic decisions (see Borgia [0094]).
Claim 30 is rejected under 35 U.S.C. 103 as being unpatentable over Beer et al. as applied to claim 28 above, and further in view of Neuman et al. (US PG-Pub 20090075832 A1) and Nakamura et al. (US PG-Pub 20090317392 A1).
Regarding claim 30, Beer et al. fails to teach the method comprising the steps:(a) obtaining an indication of the presence of metastatic lung disease in a subject by a method comprising the step: determining the presence of or level of one or more biomarkers selected from the group consisting of MAGE4A and GAGE2D polypeptides within a biological sample obtained from the subject, wherein the biological sample comprises exosomes and/or polypeptides obtained therefrom, and wherein the presence of MAGE4A and/or GAGE2D polypeptides within the biological sample is indicative of the presence of metastatic lung disease in the subject; and (b) administering a treatment appropriate for treating metastatic lung disease to the subject if an indication of the presence of metastatic lung disease in the subject is obtained, thereby treating metastatic lung disease in the subject.
However, in the analogous art of compositions and methods for classifying biological samples, Neuman et al. teaches the detection of peptide epitopes can help predict the manifestation of lung cancer and class distinction amongst at-risk patients as well as the prognosis for non-small cell lung cancer patients (see Neuman et al., Abstract, [0002]). Informative epitopes such as MAGE4A, NY-ESO, SOX-1 and SOX-2, produced an informative signal for both breast and lung cancer. For distinct classes of lung cancers, such cancer classes such as NSCLC and SCLC were viewed, as well as if the cancer is a metastatic cancer or non-metastatic cancer class. (see Neuman et al., [0044], [0147]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of diagnosing lung cancer in patients of Beer et al. by incorporating using peptide epitopes to determine lung cancer and classification including if its metastatic, using marker MAGEA4 (as taught by Neuman et al.), for the benefit of having a distinction between disease classification in order to assay treatment, in an example case where a known class of individuals may respond to chemotherapy well while another class of individuals do not respond well to chemotherapy (see Neuman et al., [0010]).
The combination of Beer et al. and Neuman et al. fails to teach administering a treatment appropriate for treating metastatic lung disease to the subject if an indication of the presence of metastatic lung disease in the subject is obtained, thereby treating metastatic lung disease in the subject.
However, in the analogous art of methods of diagnosing small cell lung cancer, Nakamura et al. teaches diagnostic methods involving determining expression level of a small cell lung cancer associated gene to distinguish with non-small cell lung cancer, and evaluating treatment efficaciousness by means of evaluating the reduction or increase in expression of a pathologically regulated gene, and the metastatic potential l of lung cancer in a subject following treatment known to have lung cancer (see Nakamura et al., Abstract, [0075]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of diagnosing metastatic lung cancer with MAGEA4 makers of the combination of Beer et al. and Neuman et al. by further incorporating treating lung cancer based on expressed potential for lung cancer to be metastatic (as taught by Nakamura et al.), for the benefit of retards or preventing additional tumors from metastatic lung cancer (see Nakamura et al., [0186]).
Claims 33-37 and 39-41 are rejected under 35 U.S.C. 103 as being unpatentable over Beer et al. as applied to claim 28 and 36 above, and further in view of Farkui et al. (US PG-Pub 20190338366 A1).
Regarding claim 33, Beer et al. teaches obtaining a biopsy tissue sample from a human subject's lung (see Beer et al., [0010]).
Beer et al. fails to teach wherein the biological sample is a bodily fluid or a liquid biopsy from the subject.
However, in the analogous art of methods for subtyping of lung squamous cell carcinoma, Faruki et al. teaches using either lung tissue samples or bodily fluids from a patient, where the bodily fluid can be blood or fractions thereof (i.e., serum, plasma), urine, saliva, sputum or cerebrospinal fluid (CSF) (see Faruki et al., [0067]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the biological sample of Beer et al. by incorporating bodily fluids as samples (as taught by Faruki et al.), for the benefit of accurately identifying the major histological types, even from small biopsies (see Farkui et al., [0067]).
Regarding claim 34, Beer et al. fails to teach wherein the biological sample is a sample of the subject's blood, saliva, bronchial lavage or urine, preferably a sample of subject's blood serum or blood plasma.
However, Faruki et al. teaches using either lung tissue samples or bodily fluids from a patient, where the bodily fluid can be blood or fractions thereof (i.e., serum, plasma), urine, saliva, sputum or cerebrospinal fluid (CSF) (see Faruki et al., [0067]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the biological sample of Beer et al. by incorporating bodily fluids as samples, including blood, saliva, urine, or blood fractions including serum or plasma (as taught by Faruki et al.), for the benefit of accurately identifying the major histological types, even from small biopsies (see Farkui et al., [0067]).
Regarding claim 35, Beer et al. fails to teach wherein the biological sample is a sample of:(i) membrane-associates polypeptides which have been obtained from exosomes from the subject, preferably exosomes from the subject's blood; or (ii) polypeptides which have been cleaved or released from the surface of exosomes from the subject, preferably exosomes from the subject's blood.
However, Faruki et al. teaches that a biomarker protein/polypeptide can be a protein encoded by or corresponding to a DNA biomarker, and that biomarker nucleic acid can be extracted from a cell or can be cell free or extracted from an extracellular vesicular entity such as an exosome sample (see Faruki et al., [0011], [0058]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the biological sample of Beer et al. to incorporate extracting nucleic acid biomarkers from an exosome, where protein/polypeptide biomarkers can correspond to certain DNA biomarkers (as taught by Beer et al.), for the benefit of determining prognosis or disease outcomes based in part on the lung squamous cell carcinoma subtype found in the patient (see Faruki et al., [0010]).
Regarding claim 36, Beer et al. teaches using antibodies specific to a polypeptide and detecting the binding of the antibody to the polypeptide in determining lung cancer. Western blot is a technique used for detecting antibody binding immobilized onto a solid support such as a nitrocellulose or a membrane. Specific markers identified by the western blot includes UCHL1 in identifying lung tumor cells, as seen expressed as 3.5-fold increase from the 2D-PAGE assessment (see Beer, [0009], [0041], [0044], [0132]). The lung cell sample is provided with a test compound, such as a therapeutic drug, and screening its effectiveness by observing a change in expression of a marker, such as UCHL1 (see Beer et al., [0017]).
However, Beer et al. fails to teach wherein the biological sample is a sample of isolated and/or purified exosomes which have been obtained from the subject.
However, Faruki et al. teaches determining a subtype of lung squamous cell carcinoma (as non-small cell lung carcinoma) by detecting the expression level of at least one classifier biomarker, such as UCHL1, at the nucleic acid level (see Faruki et al., Abstract, [0155]). The biomarker nucleic acid can be extracted from a cell or can be cell free or extracted from an extracellular vesicular entity such as an exosome (see Faruki et al., [0058]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the detection of biomarkers indicative of lung cancer and administering a therapeutic drug and assaying its effects through biomarker expression of Beer et al. by incorporating extracting the biomarkers from an exosome sample (as taught by Faruki et al.), for the benefit of accurately identifying the major histological types, even from small biopsies (see Farkui et al., [0067]).
Regarding claim 37, the examiner is interpreting the group of biomarkers to be able to consist of between one to five biomarkers, where each includes one distinct polypeptide.
The combination of Beer et al. and Farkui et al. teaches the exact limitations of claim 37. Specifically, Beer et al. teaches wherein the group of biomarkers consists of 1, 2, 3, 4, or 5 of PLD3, MAGE4A, GAGE2D, MTAP and UCHL1 polypeptides (see [0008], disclosing detecting a decreased or increased expression of a marker relative to a non-cancerous lung control sample, selected from the group UCHL1, AOE372, ATP5D, B4GALT, Ppase, GRP58, GSTM4, P4HB and TPI.).
Regarding claim 39, Beer et al. teaches obtaining a biopsy tissue sample from a human subject's lung (see Beer et al., [0010]).
Beer et al. fails to teach wherein the biological sample is a bodily fluid or a liquid biopsy from the subject.
However, Faruki et al. teaches using either lung tissue samples or bodily fluids from a patient, where the bodily fluid can be blood or fractions thereof (i.e., serum, plasma), urine, saliva, sputum or cerebrospinal fluid (CSF) (see Faruki et al., [0067]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the biological sample of Beer et al. by incorporating bodily fluids as samples, including blood, saliva, urine, or blood fractions including serum or plasma (as taught by Faruki et al.), for the benefit of accurately identifying the major histological types, even from small biopsies (see Farkui et al., [0067]).
Regarding claim 40, Beer et al. fails to teach wherein the biological sample is a sample of the subject's blood, saliva, bronchial lavage or urine, preferably a sample of subject's blood serum or blood plasma.
However, Faruki et al. teaches using either lung tissue samples or bodily fluids from a patient, where the bodily fluid can be blood or fractions thereof (i.e., serum, plasma), urine, saliva, sputum or cerebrospinal fluid (CSF) (see Faruki et al., [0067]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the biological sample of Beer et al. to incorporate extracting nucleic acid biomarkers from an exosome, where protein/polypeptide biomarkers can correspond to certain DNA biomarkers (as taught by Beer et al.), for the benefit of determining prognosis or disease outcomes based in part on the lung squamous cell carcinoma subtype found in the patient (see Faruki et al., [0010]).
Regarding claim 41, Beer et al. fails to teach wherein the biological sample is a sample of:(i) membrane-associates polypeptides which have been obtained from exosomes from the subject, preferably exosomes from the subject's blood; or (ii) polypeptides which have been cleaved or released from the surface of exosomes from the subject, preferably exosomes from the subject's blood.
However, Faruki et al. teaches that a biomarker protein/polypeptide can be a protein encoded by or corresponding to a DNA biomarker, and that biomarker nucleic acid can be extracted from a cell or can be cell free or extracted from an extracellular vesicular entity such as an exosome sample (see Faruki et al., [0011], [0058]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the detection of biomarkers indicative of lung cancer and administering a therapeutic drug and assaying its effects through biomarker expression of Beer et al. by incorporating extracting the biomarkers from an exosome sample (as taught by Faruki et al.), for the benefit of accurately identifying the major histological types, even from small biopsies (see Farkui et al., [0067]).
Claim 38 is rejected under 35 U.S.C. 103 as being unpatentable over Beer et al. and Faruki et al. as applied to claim 36 above, and further in view of Borgia.
Regarding claim 38, the combination of Beer et al. and Faruki et al. fails to teach wherein the group of biomarkers consists of:(i) PLD3; (ii) MTAP; or (iii) PLD3 and MTAP.
However, Borgia teaches determining whether or not a mammal has NSCLC versus non-NSCLC lung cancer or benign lung diseases, where the mammal is evaluated to have an elevated level of expression of one or more nucleic acids, or a polypeptide encoded by the nucleic acid or an autoantibody to said polypeptide, selected from a group which includes methylthioadenosine phosphorylase (MTAP). The presence or absence of an elevated level is used to determine treatment for a lung cancer such as NSCLC, especially those with early stage lung cancer such as Stage I, identified during patient prognostication (see Borgia, Abstract, [0015]-[0016])
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of diagnosing lung cancer in patients of the combination of Beer et al. and Faruki et al. by incorporating obtaining the expression of MTAP as a biomarker (as taught by Borgia), for the benefit of obtaining critical prognostic information for non-small cell lung cancer patients for guiding therapeutic decisions (see Borgia [0094]).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Tracy C Colena whose telephone number is (571)272-1625. The examiner can normally be reached Mon-Thus 8:00am-5:00pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lyle Alexander can be reached at (571) 272-1254. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TRACY CHING-TIAN COLENA/ Examiner, Art Unit 1797
/JENNIFER WECKER/ Primary Examiner, Art Unit 1797
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