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 .
Claim Status
Claims 1-24 are pending and being examined on the merits.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement (for example, pg 15, ln 1-2). 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Requirement for Information under 37 CFR 1.105
Applicant and the assignee of this application are required under 37 CFR 1.105 to provide the following information that the examiner has determined is reasonably necessary to the examination of this application. The examiner found that a poster presentation was given at the 106th Annual Meeting of The American Association for Cancer Research (AACR) April 18-22, 2015 by a named inventor on the instant application (Irene Oi-Lin Ng) titled “S100A10 as a novel biomarker in hepatocellular carcinoma” (see attached conference abstract, published on August 1, 2015 in Cancer Research). The abstract indicates that there was a public disclosure of the claimed overexpression of the HCC biomarker (S100A10).
The examiner requires further information in order to make further determinations about the patentability to the instant claims. In response to this requirement, please provide the following answers and materials:
1. Were forms of determination of S100A10 levels presently claimed (e.g., ELISA, RIA, Western, dot blot, RT-PCR, qPCR) publicly disclosed at the 106th Annual Meeting of The American Association for Cancer Research (AACR)? Additionally, was treatment of cells with a therapeutic agent publicly disclosed?
2. Please provide a copy of the poster presentation titled “S100A10 as a novel biomarker in hepatocellular carcinoma” (Abstract 533) given within April 18-22, 2015, and
3. Any additional presentation materials (such as a slide deck) that may have been presented at this conference.
The fee and certification requirements of 37 CFR 1.97 are waived for those documents submitted in reply to this requirement. This waiver extends only to those documents within the scope of this requirement under 37 CFR 1.105 that are included in the applicant’s first complete communication responding to this requirement. Any supplemental replies subsequent to the first communication responding to this requirement and any information disclosures beyond the scope of this requirement under 37 CFR 1.105 are subject to the fee and certification requirements of 37 CFR 1.97.
The applicant is reminded that the reply to this requirement must be made with candor and good faith under 37 CFR 1.58. Where the applicant does not have or cannot readily obtain an item of required information, a statement that the item is unknown or cannot be readily obtained may be accepted as a complete reply to the requirement for that item. This requirement is an attachment of the enclosed Office action. A complete reply to the enclosed Office action must include a complete reply to this requirement. The time period for reply to this requirement coincides with the time period for reply to the enclosed Office action.
Drawings
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Specification
The disclosure is objected to because of the following informalities:
Pg 3, ln 6-7: “ii) determining that the level of S100A10 in the sample compared to a control” should read “ii) determining [[that]] the level of S100A10 in the sample compared to a control”.
Pg 3, ln 10-11: “the subject diagnosed as having HCC has a level of S100A10 is at least 10%” should read “the subject diagnosed as having HCC has a level of S100A10 [[is]] at least 10%”.
Pg 3, ln 17: “the step of determining that the level of S100A10 in the sample includes measuring” should read “the step of determining [[that]] the level of S100A10 in the sample includes measuring”.
Pg 10, ln 21-22: The figures are described with reference to specific colors in the figures (“as seen in red color”, “DAPI (blue)”). Unless a petition is filed to include color drawings, the presented figures will be in black and white and thus references to color in the figures should be avoided.
There are numerous similar examples as those above throughout the specification, which should be carefully read through and corrected.
Appropriate correction is required.
The use of the terms “Texas Red” (pg 44, ln 23) and “Alexa Fluor” (pg 44, ln 25), which are trade names or marks used in commerce, have been noted in this application. These terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
The examples above are not an exhaustive list of unmarked trade names or marks used in commerce throughout the specification. Please carefully read through and properly notate each instance.
Claim Objections
Claims 6, 8, 9, 10, and 16 are objected to because of the following informalities:
Claim 6 reads “The method of any clam 1” and should most likely read “The method of [[any clam 1]]claim 1”.
Claim 8 reads “wherein the step of identifying the subject as having HCC is such identification with at least” and should read “wherein the step of identifying the subject as having HCC is [[such]]an identification with at least”.
Claim 9 reads “further comprising the step of treating the identified subject” and should read “further comprising [[the]]a step of treating the [[identified]] subject identified as having HCC” to improve clarity. The edit makes it clear that this is a new step being added to the method of claim 1, and reiterates that the treatment is being applied specifically to the subject that is identified as having HCC.
Claim 10 reads “wherein the small molecules are effective” and should read “wherein the small [[molecules]]molecule inhibitors are effective” to remain consistent with the claim language in claim 9, from which it depends.
Claim 16 reads “wherein the small molecules are effective” and should read “wherein the small [[molecules]]molecule inhibitors are effective”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112b - Indefinite
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.
Claims 1-24 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.
Claim 1 is directed to “a method for identifying a subject as having an elevated risk of having hepatocellular carcinoma” (emphasis added). However, line 4 requires a step of “identifying the subject as having HCC if the level of S100A10 in the sample is increased compared to the level of S100A10 in a control sample”. It is unclear what the scope of the claim is, given that the purpose of the method in the preamble is to identify as subject as having “an elevated risk” of having HCC, whereas the identifying step identifies as a subject as having HCC. An elevated risk of having HCC and having HCC are not the same, therefore the claim is indefinite. Additionally, there is no active step of detecting an increased amount of S100A10 in a sample compared to the control, meaning that identification step is conditional upon something that is not required to be present (increased levels of S100A10).
Claim 1 recites the limitation "the sample" in lines 3 and 4. There is insufficient antecedent basis for this limitation in the claim.
Claim 1 recites the limitation “identifying the subject as having HCC if the level of S100A10 in the sample is increased compared to the level of S100A10 in a control sample”. However, it is unclear what is being considered a “control sample”. No definition of a control is provided in the specification, only an example of a control being a healthy subject. However, a control can be any sample with a known amount/level of S100A1, meaning that the control could be anything from individuals with extremely low S100A10 levels or extremely high S100A10 levels, which would dramatically alter the outcomes/scope of claim 1.
Claims 2-12 depend from claim 1, inherit these deficiencies, and are rejected on the same basis.
Claim 2 recites the limitation "the sample" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 5 recites the limitation "the sample" in lines 2 and 3. There is insufficient antecedent basis for this limitation in the claim. Claim 5 also recites the limitation “the extracellular vesicles” in line 3. There is insufficient antecedent basis for this limitation in the claim.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 5 recites the broad recitation “measuring the level of S100A10 protein in the sample”, and the claim also recites “preferably, level of S100A10 protein derived from the extracellular vesicles of the sample” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 6 recites the limitation "the sample" in lines 2 and 5. There is insufficient antecedent basis for this limitation in the claim.
Claim 6 is directed to the method of claim 1 in which determining the level of S100A10 in the sample involves performing ELISA, RIA, western blot, dot blot, AND measuring the level of S100A10 mRNA in the sample. However, it is unclear how the levels determined from each of these individual methods is combined to receive a final outcome of the level of S100A10 in the sample to be compared to a control. It is unclear how measurements involving protein levels and mRNA levels are being combined to arrive at a single determined level of S100A10. Clarification is required.
Claim 7 depends from claim 6, inherits this deficiency, and is rejected on the same basis.
Claim 13 recites the limitation of administering a therapeutic agent to a subject “if the level of S100A10 in the sample is increased compared to the level of S100A10 in a control sample”. However, it is unclear what is being considered a “control sample”. No definition of a control is provided in the specification, only an example of a control being a healthy subject. However, a control can be any sample with a known amount/level of S100A1, meaning that the control could be anything from individuals with extremely low S100A10 levels or extremely high S100A10 levels, which would dramatically alter the outcomes/scope of claim 13.
Claim 13 is directed to a method of treating a subject having HCC, however, the administration of a treatment is conditional (i.e., “administering to the subject an effective amount of a therapeutic agent for treating HCC if the level of S100A10 in the sample is increased compared to the level of S100A10 in a control sample” (emphasis added). The increased level of S100A10 is not required by the claim, therefore it is unclear how the method of treating the subject is accomplished if an increased amount of S100A10 is NOT detected in the sample.
Claims 14-24 depend from claim 13, inherit this deficiency, and are rejected on the same basis.
Claim 16 recites the limitation "the small molecules" in line 1. There is insufficient antecedent basis for this limitation in the claim. No small molecules are defined in claim 13, from which claim 16 depends.
Claim 17 recites the limitation "the antibodies" in line 1. There is insufficient antecedent basis for this limitation in the claim. No antibodies are defined in claim 13, from which claim 17 depends.
Claim 18 recites the limitation "the inhibitory nucleic acids" in line 1. There is insufficient antecedent basis for this limitation in the claim. No inhibitory nucleic acids are defined in claim 13, from which claim 18 depends.
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 1-24 are rejected under 35 U.S.C. 101 because the claimed invention is directed to abstract ideas (e.g.: mental processes) and a natural phenomenon without significantly more.
The claims recite methods of identifying a subject as having HCC if S100A10 levels are increased compared to a control (as recited in claims 1 and 13) with a step of measuring S100A10 levels. The claims are thus directed to the assessment of collected data, which is an abstract idea that is a mental process (e.g.: MPEP 2106.04(a (2)(III)(A)); it is the observation and evaluation of information to reach a judgment or conclusion, as set forth in claim 1 and 13). Claims 1 and 13 recite a step of comparing (“compared to the level of S100A10 in a control sample”) which is a mental evaluation of data. Where the evaluation of data to reach a conclusion is based in the asserted correlation between gene levels and the presence of a particular pathology, such an association is an accepted part of how a biological organism functions (i.e.: genotype:phenotype relationships), and as such this element of the claims is a natural phenomenon (e.g.: MPEP 2106.04(b)(I)).
This judicial exception is not integrated into a practical application. Even though claim 9 (depending from claim 1) and claim 13 recite a step of administering a therapeutic agent for treating HCC, the scope of the claims also encompasses the subject not being identified as having HCC (“if the levels of S100A10 in the sample is increased”, emphasis added), therefore they do not require the administration of a therapeutic agent. There are no additional steps of the claims that are directed to applying or using the judicial exceptions noted above (e.g.: MPEP 2106.04(d)(I)). The claims end with an asserted association between a gene level and the presence of a pathology, which is an abstract idea (as noted above).
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims only broadly recite steps of determining the level of S100A10 in a sample by measuring the level of S100A10 protein and mRNA. However, such steps were well understood, routine and conventional in the prior art (e.g.: MPEP 2106.05(d)). For example: Zhou et al. teaches measuring mRNA levels (via RT-qPCR, Figure 3A) and protein levels (via Western blotting, Figure 3B) of S100A10 and also describes mining publicly available gene expression and protein expression data bases (OEP000321 and TCGA) that provided information on both gene expression and protein expression of S100A10 in HCC samples (Zhou et al., 2021; cited on IDS of 4/24/2024).
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.
(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 1-2, 4-5, and 8-12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhou (Zhou et al., Frontiers in Genetics 2021; cited on IDS of 4/24/2024).
As noted in the 112b rejection of claim 1 above, there is no active step of detecting an increased amount of S100A10 in a sample compared to the control, meaning that identification step is conditional upon something that is not required to be present (increased levels of S100A10). Additionally, what constitutes a “control sample” is not clearly defined in the claim or in the specification, meaning that anything can be considered as a control. As such, claim 1 explicitly requires determining the level of S100A10 in a sample and comparing it to any other sample as a control and determining either decreased or increased levels of S100A10 between the two.
Claims 1, 4, and 8-12: Zhou teaches determining the protein level and mRNA level of S100A10 in samples obtained from a subject (claim 1; “we re-analyzed the gene expression profile and the protein expression profile (OEP000321) obtained from Fan’s study”, pg 4, col 1-2). Zhou teaches determining decreased levels of S100A10 in a sample compared to another sample (Figure 2A). As shown in Figure 2A, N, there are some samples that exhibit lower expression of S100A10 as compared to another N sample. The detection of decreased levels of S100A10 therefore does not require that the level of S100A10 is at least 10% greater than the control (claim 4), does not result in identification of HCC in a subject with a specific identification certainty (claim 8) and thus does not require treatment of said subject with a therapeutic agent for treating HCC (claims 9-12).
Claim 2: The data obtained from OEP000321 was from tumor and non-tumor samples from the same subject obtained through liver biopsies (pg 4, col 1-2).
Claim 5: Zhou teaches determining the level of S100A10 protein in HCC samples (“protein expression profile (OEP000321) obtained from Fan’s study”; pg 4, col 1).
Claims 13-24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhou (Zhou et al., Frontiers in Genetics 2021; cited on IDS of 4/24/2024).
As noted in the 112b rejection of claim 13 above, there is no active step of detecting an increased amount of S100A10 in a sample compared to the control, meaning that the administration of a therapeutic agent is conditional upon something that is not required to be present (increased levels of S100A10). Additionally, what constitutes a “control sample” is not clearly defined in the claim or in the specification, meaning that anything can be considered as a control. As such, claim 13 only explicitly requires determining the level of S100A10 in a sample and comparing it to any other sample as a control and determining either decreased or increased levels of S100A10 between the two.
Zhou teaches determining the level of S100A10 in samples obtained from a subject (claim 1; “we re-analyzed the gene expression profile and the protein expression profile (OEP000321) obtained from Fan’s study”; pg 4, col 1-2). Zhou teaches determining decreased levels of S100A10 in a sample compared to another sample (Figure 2A). As shown in Figure 2A, N, there are some samples that exhibit lower expression of S100A10 as compared to another N sample. The detection of decreased levels of S100A10 therefore does not require that the level of S100A10 is at least 10%-more than 100% greater than the control (claim 14) and thus does not require treatment of said subject with a therapeutic agent for treating HCC (claims 15-24).
Claims 1-2, 4-5, and 8-12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chiu (Chiu et al., Cancer Research 2015).
As noted in the 112b rejection of claim 1 above, there is no active step of detecting an increased amount of S100A10 in a sample compared to the control, meaning that identification step is conditional upon something that is not required to be present (increased levels of S100A10). Additionally, what constitutes a “control sample” is not clearly defined in the claim or in the specification, meaning that anything can be considered as a control. As such, claim 1 explicitly requires determining the level of S100A10 in a sample and comparing it to any other sample as a control and determining either decreased or increased levels of S100A10 between the two.
Claims 1, 4, and 8-12: Chiu teaches determining levels of S100A10 in samples obtained from a subject (claim 1; “We evaluated S100A10 expression in human HCC and the corresponding non-tumorous liver (NT) tissues in a cohort of 67 HCC patients by RT-PCR”; Experimental Procedures). Chiu teaches that S100A10 is not overexpressed (increased) in some samples compared to others (Results). The detection of decreased levels of S100A10 therefore does not require that the level of S100A10 is at least 10% greater than the control (claim 4), does not result in identification of HCC in a subject with a specific identification certainty (claim 8) and thus does not require treatment of said subject with a therapeutic agent for treating HCC (claims 9-12).
Claim 2: Chiu teaches that the sample is a liver biospy (“in human HCC and the corresponding non-tumorous liver (NT) tissues”, Experimental Procedures).
Claim 5: Chiu teaches determining the level of S100A10 protein in HCC samples (“evaluated S100A10 mRNA and protein expression”; Experimental Procedures).
Claims 13-24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chiu (Chiu et al., Cancer Research 2015).
As noted in the 112b rejection of claim 13 above, there is no active step of detecting an increased amount of S100A10 in a sample compared to the control, meaning that the administration of a therapeutic agent is conditional upon something that is not required to be present (increased levels of S100A10). Additionally, what constitutes a “control sample” is not clearly defined in the claim or in the specification, meaning that anything can be considered as a control. As such, claim 13 only explicitly requires determining the level of S100A10 in a sample and comparing it to any other sample as a control and determining either decreased or increased levels of S100A10 between the two.
Chiu teaches determining levels of S100A10 in samples obtained from a subject (claim 13; “We evaluated S100A10 expression in human HCC and the corresponding non-tumorous liver (NT) tissues in a cohort of 67 HCC patients by RT-PCR”; Experimental Procedures). Chiu teaches that S100A10 is not overexpressed (increased) in some samples compared to others (Results). The detection of decreased levels of S100A10 therefore does not require that the level of S100A10 is at least 10%-more than 100% greater than the control (claim 14) and thus does not require treatment of said subject with a therapeutic agent for treating HCC (claims 15-24).
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.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Zhou (Zhou et al., Frontiers in Genetics 2021; cited on IDS of 4/24/2024) as applied to claims 1-2, 4-5, and 8-12 above, in view of Kittaka (Kittaka et al., European Journal of Cancer 2008).
Zhou teaches determining levels of S100A10 in samples obtained from tumor and adjacent non-tumor biopsies. Zhou does not teach that the control samples are from a healthy subject.
However, determining S100A10 samples and comparing to a control sample from a healthy subject is known in the art, as taught by Kittaka.
Kittaka teaches determining levels of S100A10 in HCC tumors from patients and evaluated gene expression changes in HCC samples compared to normal control samples (3.1. Microarray analysis of gene expression changes in HCC tumours).
It would have been prima facie obvious to one having ordinary skill in the art, before the effective filing date of the instant application, to have modified the method of Zhou to compare sample liver to healthy liver, as taught by Kittaka. One would be motivated to do so given the teaching by Zhou that a limitation of their study is that S100A10 levels should be assessed in normal liver cells (pg 7, col 1, paragraph 3). One would have a reasonable expectation of success given that Kittaka teaches that S100A10 levels can successfully be measured in both HCC tumor cells and liver cells obtained from a healthy individual (normal liver; Fig 1B).
Claims 6-7 are rejected under 35 U.S.C. 103 as being unpatentable over Zhou (Zhou et al., Frontiers in Genetics 2021; cited on IDS of 4/24/2024) as applied to claims 1-2, 4-5, and 8-12 above, and further in view of Caprioli (US 20070031900 A1) and Thermo Fisher (Application Note, Protein analysis technologies, 2018).
The teachings of Zhou are detailed above. Relevant to the instantly rejected claims, Zhou teaches a method of determining S100A10 protein levels by performing a western blot (claim 6; Fig 3B and pg 2, col 2 Western Blotting) and determining the levels of S100A10 mRNA via RT-PCR (claim 6 and 7; Fig 3A and pg 2, col 2 Real-Time Quantitative PCR).
Zhou does not teach determining the levels of S100A10 in a sample by performing an enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA), and dot blot in addition to the western blot. However, use of multiple different immunoassays for measuring protein levels is known in the art, as taught by Caprioli.
Caprioli teaches measuring protein levels in patient samples of gliomas, and teaches that one such protein is S100A10 (Abstract and paragraph [0031]). Caprioli teaches ELISA, RIA, western blot, and dot blot as immunoassays used to measure protein levels (paragraphs [0083-0087 and 0093]).
It would have been prima facie obvious to one having ordinary skill in the art, before the effective filing date of the instant application, to have modified the method of Zhou (who teaches measuring protein levels with western blots) to additionally measure protein levels by ELISA, RIA, and dot blots as taught by Caprioli. One would be motivated to use multiple different detection methods given the teaching by ThermoFisher that using multiple types of protein detection methods provides confidence in the obtained results (pg 6, col 2). One would have a reasonable expectation of success in using all 4 methodologies given the teaching by Caprioli that “the detection of immunocomplex formation is well known in the art and may be achieved through the application of numerous approaches” (paragraph [0088]).
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Chiu (Chiu et al., Cancer Research 2015) as applied to claims 1-2, 4-5, and 8-12 above, and further in view of Kittaka (Kittaka et al., European Journal of Cancer 2008) and Zhou (Zhou et al., Frontiers in Genetics 2021; cited on IDS of 4/24/2024).
Chiu teaches determining levels of S100A10 in samples obtained from tumor and adjacent non-tumor biopsies. Chiu teaches that the control in this case to compare S100A10 levels to is to corresponding non-tumorous liver samples. Chiu does not teach that the control samples are from a healthy subject.
However, determining S100A10 samples and comparing to a control sample from a healthy subject is known in the art, as taught by Kittaka.
Kittaka teaches determining levels of S100A10 in HCC tumors from patients and evaluated gene expression changes in HCC samples compared to normal control samples (3.1. Microarray analysis of gene expression changes in HCC tumours).
It would have been prima facie obvious to one having ordinary skill in the art, before the effective filing date of the instant application, to have modified the method of Chiu (who teaches comparing tumor and adjacent non-tumor samples) to compare tumorous liver to healthy liver, as taught by Kittaka. One would be motivated to do so given the teaching by Zhou that a limitation of their study is that S100A10 levels should be assessed in normal liver cells (pg 7, col 1, paragraph 3). One would have a reasonable expectation of success given that Kittaka teaches that S100A10 levels can successfully be measured in both HCC tumor cells and liver cells obtained from a healthy individual (normal liver; Fig 1B).
Claims 6-7 are rejected under 35 U.S.C. 103 as being unpatentable over Chiu (Chiu et al., Cancer Research 2015) as applied to claims 1-2, 4-5, and 8-12 above, and further in view of Caprioli (US 20070031900 A1) and Thermo Fisher (Application Note, Protein analysis technologies, 2018).
The teachings of Chiu are detailed above. Relevant to the instantly rejected claims, Chiu teaches determining S100A10 protein levels (claim 6; Experimental Procedures) and determining the levels of S100A10 mRNA via RT-PCR (claim 6 and 7; Experimental Procedures).
Chiu does not teach the method for determining the levels of S100A10 in a sample by performing an enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA), western blot and dot blot. However, use of multiple different immunoassays for measuring protein levels is known in the art, as taught by Caprioli.
Caprioli teaches measuring protein levels in patient samples of gliomas, and teaches that one such protein is S100A10 (Abstract and paragraph [0031]). Caprioli teaches ELISA, RIA, western blot, and dot blot as immunoassays used to measure protein levels (paragraphs [0083-0087 and 0093]).
It would have been prima facie obvious to one having ordinary skill in the art, before the effective filing date of the instant application, to have modified the method of Chiu (who teach measuring protein levels) to measure protein levels by ELISA, RIA, western blot and dot blot as taught by Caprioli. One would be motivated to use multiple different detection methods given the teaching by ThermoFisher that using multiple types of protein detection methods provides confidence in the obtained results (pg 6, col 2). One would have a reasonable expectation of success in using all 4 methodologies given the teaching by Caprioli that “the detection of immunocomplex formation is well known in the art and may be achieved through the application of numerous approaches” (paragraph [0088]).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAILEY E CASH whose telephone number is (571)272-0971. The examiner can normally be reached Monday-Friday 8:30am-6pm ET.
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/KAILEY ELIZABETH CASH/Examiner, Art Unit 1683
/STEPHEN T KAPUSHOC/Primary Examiner, Art Unit 1683