Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
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.
DETAILED ACTION
Responsive to communications entered 09/16/2025.
Priority
This application, filed 12/13/2023, Pub. No. US 2024/0361322 A1, published 10/31/2024, is a continuation of US application 16/748,026, filed 01/21/2020, Pub. No. US 2020/0158731 A1, now abandoned, which is a division of US application 15/440,136, filed 02/23/2017, Pub. No. US 2017/0160281 A1, now abandoned, which is a continuation of US application 14/168,590, filed on 01/30/2014, Pub. No. US 2014/0220006 A1, now abandoned, which claims benefit of U.S. Provisional Application No. 61/759,436, filed on 02/01/2013.
Status of Claims
Claims 27-43 and 45 are currently pending. Claims 1-25 have been originally filed. Claims 1-25 have been cancelled, and Claim 26 has been added, as set forth in the 1st Preliminary amendment filed 12/13/2023. Claim 26 has been cancelled, and Claims 27-45 have been added, as set forth in the 2nd Preliminary amendment filed 07/18/2024. Claims 27-45 have been subject to the species election requirement mailed 04/16/2025. Claims 27-32, 35-38, 41-43 and 45 have been amended, and Claim 44 has cancelled, as set forth in Applicant’s amendment filed 09/16/2025. Claims 29, 39 and 43 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Claims 27, 28, 30-38, 40-42 and 45 are examined.
Election/Restriction
Applicant's election, without traverse, the species:
(a) a well as an assay chamber;
(b) serum as a test sample;
(c) Capillary Isoelectric Focusing (CLEF) as an analytical testing method; and
(d) MDC, NME-2, KGF and PIGF as 4 biomarkers,
in the reply filed on 09/16/2025 is acknowledged.
Applicant identified Claims 27-43 and 45 as encompassing the elected species. With regard to Claims 29, 39 and 43, the Examiner respectfully disagrees with Applicant’s assessment because Claims 29 and 39 do not read on the elected species (a), whereas Claim 43 does not read on the elected species (b).
Claims 29, 39 and 43 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 09/16/2025.
Information Disclosure Statement
The information disclosure statement filed 12/13/2023 fails in part to comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609 because for applications filed before September 16, 2012, the inventor name shall be listed in column “Name of Patentee or Applicant” for U.S. Patent Application Publications. See MPEP § 605. It has been placed in the application file, but the information referred to therein has not been considered as to the merits. Applicant is advised that the date of any re-submission of any item of information contained in this information disclosure statement or the submission of any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the statement, including all certification requirements for statements under 37 CFR 1.97(e). See MPEP § 609.05(a).
Specification
The use of the term MSD® and MULTI-ARRAY®, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
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.
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Claim Rejection - 35 USC § 112
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 112 that form the basis for the rejections under this section made in this Office action:
The following is a quotation of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), first paragraph:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention.
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 27, 28, 30-38, 40-42 and 45 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention (“new matter”).
The claims, as recited in independent Claim 27, are drawn to:
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There appears to be no support for recitation “a non-transitory computer readable medium having stored thereon a computer program configured to measure, with a multiplexed immunoassay, levels of a plurality of at least four biomarkers selected from the group consisting of NME-2, Flt-3L, MDC, KGF, P1GF, HGF, MCP1, SAT-1, MIP-1-b, GCLM, OPG, TNF RII, VEGF-D, ITAC, MMP-10, GPI, PPP2R4, AKR1B1, Amy1A, MIP-1b, P-Cadherin, and EPO, and combinations thereof in a sample from a human subject, causes the computer system to perform a method of monitoring lung cancer in a patient” (Emphasis added) in Claim 27, because the disclosure concerning the use of “computer” is limited to the following paragraph:
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Page 9 of the specification filed 12/13/2023; Emphasis added.
According to MPEP 2163.06, “If new matter is added to the claims, the Examiner should reject the claims under 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph - written description requirement. In re Rasmussen, 650 F.2d 1212, 211 USPQ 323 (CCPA 1981).” MPEP 2163.02 teaches that “Whenever the issue arises, the fundamental factual inquiry is whether a claim defines an invention that is clearly conveyed to those skilled in the art at the time the application was filed...If a claim is amended to include subject matter, limitations, or terminology not present in the application as filed, involving a departure from, addition to, or deletion from the disclosure of the application as filed, the examiner should conclude that the claimed subject matter is not described in that application.”
Claims 27, 28, 30-38, 40-42 and 45 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 applicant regards as the invention.
Claims 27 is indefinite because the preamble of the claim is drawn to a non-transitory computer readable medium; however, the body of the claim recites active method steps for monitoring lung cancer in a patient. Since Claims 27 encompasses both a product and the method of using the product, it is indefinite under 35 U.S.C. 112(b). See MPEP 2173.05(p). The claim is considered indefinite because one of ordinary skill in the art would not be able to ascertain whether the claim is directed to a non-transitory computer readable medium or a method performed by the computer system. Claims 28, 30-38, 40-42 and 45 are rejected as being dependent upon the rejected Claim 27 and fail to cure the indefiniteness of Claim 28.
Claim 27 recites the limitation "the computer system" in line 6. There is insufficient antecedent basis for this limitation in the claim because there is no earlier recited computer system. Claims 28, 30-38, 40-42 and 45 are rejected as being dependent upon the rejected Claim 27 and fail to cure the indefiniteness of Claim 28.
Claim 27 recites the limitation "(a) receiving a measurement of a level of a plurality of biomarkers in a test sample from a patient". There is insufficient antecedent basis for this limitation in the claim because the preamble of the claim is drawn to measuring level of a plurality of at least four of biomarkers selected from the group consisting of NME-2, Flt-3L, MDC, KGF, P1GF, HGF, MCP1, SAT-1, MIP-1-b, GCLM, OPG, TNF RII, VEGF-D, ITAC, MMP-10, GPI, PPP2R4, AKR1B1, Amy1A, MIP-1b, P-Cadherin, and EPO, and combinations thereof in a sample from a human subject. Emphasis added. Claims 28, 30-38, 40-42 and 45 are rejected as being dependent upon the rejected Claim 27 and fail to cure the indefiniteness of Claim 28.
Claim 28 recites the limitation "said human analytes" in line 12. There is insufficient antecedent basis for this limitation in independent Claim 27. Claims 30-32 and 45 are rejected as being dependent upon the rejected Claim 28 and fail to cure the indefiniteness of Claim 28.
Claim 28 contains the trademark/trade name EXPERION™, and Claim 35 contains the trademark/trade name an MSD® MULTI-ARRAY® 96-well plate and an MSD® plate reader. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe automated electrophoresis, a well plate and a plate reader and, accordingly, the identification/description is indefinite. Claims 30-32 and 45 are rejected as being dependent upon the rejected Claim 28 and fail to cure the indefiniteness of Claim 28.
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 27, 28, 30-38, 40-42 and 45 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
Step 1: This part of the eligibility analysis evaluates whether the claim falls within any statutory category. MPEP § 2106.03. The claims are drawn to a non-transitory computer readable medium. Thus, the claims are directed to a manufacture, which is one of the statutory categories of invention (Step 1: YES).
Step 2A Prong One: This part of the eligibility analysis evaluates whether the claim recites a judicial exception. As explained in MPEP § 2106.04(II), a claim “recites” a judicial exception when the judicial exception is “set forth” or “described” in the claim. While the terms "set forth" and "described" are thus both equated with "recite", their different language is intended to indicate that there are two ways in which an exception can be recited in a claim. For instance, the claims in Diehr, 450 U.S. at 178 n. 2, 179 n.5, 191-92, 209 USPQ at 4-5 (1981), clearly stated a mathematical equation in the repetitively calculating step, and the claims in Mayo, 566 U.S. 66, 75-77, 101 USPQ2d 1961, 1967-68 (2012), clearly stated laws of nature in the wherein clause, such that the claims “set forth” an identifiable judicial exception. Alternatively, the claims in Alice Corp., 573 U.S. at 218, 110 USPQ2d at 1982, described the concept of intermediated settlement without ever explicitly using the words “intermediated” or “settlement.” Here, based upon an analysis with respect to the claim as a whole, the instant claims are determined to be directed to a law of nature/natural principle and an abstract idea. The relationship between the recited biomarkers and the lung cancer of a patient is a natural principle, which is a judicial exception. Limitation (a) “receiving a measurement” in Claim 27 recites a law of nature because it describes the naturally occurring correlation between the measured level of a plurality of at least four of biomarkers selected from the group consisting of NME-2, Flt-3L, MDC, KGF, P1GF, HGF, MCP1, SAT-1, MIP-1-b, GCLM, OPG, TNF RII, VEGF-D, ITAC, MMP-10, GPI, PPP2R4, AKR1B1, Amy1A, MIP-1b, P-Cadherin, and EPO, and combinations thereof in a sample from a human subject, and lung cancer. In addition, Claim 27 recites “(b) comparing said level of said plurality of biomarkers and a normal control level of said plurality of biomarkers”; and “evaluating from said comparing step (b) that the patient will be is responsive to said treatment regimen.” It should be noted that the recitation of a computer system in this claim does not negate the mental nature of these limitations because the claim here merely uses the computer system as a tool to perform the otherwise mental processes. If a claim limitation under its broadest reasonable interpretation, covers performance of the limitation in the mind but for the recitation of generic computer components, then it is still in the mental processes grouping unless the claim limitation cannot practically be performed in the mind. Therefore, the “comparing” and “evaluating” steps are a recitation of an abstract idea (judicial exception).
Accordingly, the claims recite a judicial exception (both a law of nature and abstract idea).
Accordingly, Claim 54 recites a judicial exception (an abstract idea that falls within
the mental process grouping and a law of nature).
Step 2A Prong Two: This part of the eligibility analysis evaluates whether the claim as a whole integrates the recited judicial exception into a practical application of the exception. This evaluation is performed by (a) identifying whether there are any additional elements recited in the claim beyond the judicial exception, and (b) evaluating those additional elements individually and in combination to determine whether the claim as a whole integrates the exception into a practical application.
Besides the abstract idea/law of nature, Claim 27 recites an additional element that requires performance of method steps using computer hardware and/or constitute computer hardware that implements claimed functions. However, Claim 27 does not describe any specific computational steps by which computer hardware performs or carries out the abstract idea, nor does it provide any details of how specific structures of computer hardware are used to implement claimed “receiving a measurement of a level of a plurality of biomarkers in a test sample”; “comparing said level of said plurality of biomarkers and a normal control level of said plurality of biomarkers”; and “evaluating from said comparing step (b) that the patient will be is responsive to a treatment regimen.” There are no limitations that indicate that the claimed steps require anything other than generic computing systems. The claim states nothing more than that computer hardware performs the functions that constitute the abstract idea, and are therefore mere instructions to apply the abstract idea using generic computer hardware. (MPEP 2106.05(f)). The computer readable medium executed on a computer system is recited so generically that it represents no more than mere instructions to apply the judicial exception in the computer readable medium. These limitations can also be viewed as nothing more than an attempt to generally link the use of the judicial exception to the technological environment of a computer. It should be noted that because the courts have made it clear that mere physicality or tangibility of an additional element or elements is not a relevant consideration in the eligibility analysis, the physical nature of these computer components does not affect this analysis. See MPEP 2106.05(I) for more information on this point, including explanations from judicial decisions including Alice Corp. Pty. Ltd. v. CLS Bank Int'l, 573 U.S. 208, 224-26 (2014).
Even when viewed in combination, the additional elements in this claim do no more than automate the mental processes that a doctor used to perform (e.g., the mental inspection and evaluation of biomarker levels), using the computer readable medium executed by a computer system as a tool. While this type of automation improves the doctors’ job (by minimizing or eliminated the need for mentally evaluating the biomarker levels), there is no change to the computer readable medium and other technology that is recited in the claim as automating the abstract ideas, and thus, this claim cannot improve computer functionality or other technology. See, e.g., Trading Technologies Int’l v. IBG, Inc., 921 F.3d 1084, 1093 (Fed. Cir. 2019) (using a computer to provide a trader with more information to facilitate market trades improved the business process of market trading, but not the computer) and the cases discussed in MPEP 2106.05(a)(I), particularly FairWarning IP, LLC v. Iatric Sys., 839 F.3d 1089, 1095 (Fed. Cir. 2016) (accelerating a process of analyzing audit log data is not an improvement when the increased speed comes solely from the capabilities of a general-purpose computer) and Credit Acceptance Corp. v. Westlake Services, 859 F.3d 1044, 1055 (Fed. Cir. 2017) (using a generic computer to automate a process of applying to finance a purchase is not an improvement to the computer’s functionality). Accordingly, the claim as a whole does not integrate the recited judicial exception into a practical application and the claim is directed to the judicial exception. As such, Claim 27 does not integrate that abstract idea into a practical application (MPEP § 2106.04(d) and 2106.05(f)).
Claim 27 further recites the additional elements of “configured to measure, with a multiplexed immunoassay, levels of a plurality of at least four biomarkers”. However, steps of obtaining/detecting are insufficient to integrate the judicial exception(s) into a practical application because the purpose is merely to obtain data. This does not go beyond insignificant presolution activity, i.e., a mere data gathering step necessary to use the correlation, similar to the fact pattern in In re Grams, 888 F.2d 835 (Fed. Cir. 1989) and Ariosa Diagnostics, Inc. v. Sequenom, Inc. (Fed. Cir. 2015). Such steps that merely “add insignificant extra-solution activity to the judicial exception” are insufficient to integrate the exception into a practical application (MPEP 2106.05(g)). Data gathering steps typically constitute such insignificant extra-solution activity. See Mayo (concluding that additional element of measuring metabolites of a drug administered to a patient was extra-solution activity); OIP Techs., Inc. v. Amazon.com, Inc., 788 F.3d 1359, 1363 (Fed. Cir. 2015) (holding that mere data gathering is insufficient to confer patent eligibility). In addition, these limitations fail to meaningfully limit the claim because they do not provide any information as to how the “measurement” is conducted. In fact, these limitations are recited at a high level of generality, making the limitations’ inclusion in this claim at best nominal.
The further defined additional elements recited in the claims, do not represent an improvement to a technical field, as such techniques were previously known (see discussion below), and, accordingly, do not apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception.
Accordingly, these limitations do not integrate the recited judicial exception into a practical application and the claims are therefore directed to the judicial exception (Step
2A: YES).
Step 2B: This part of the eligibility analysis evaluates whether the claim as a whole amounts to significantly more than the recited exception, i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim. See MPEP § 2106.05.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception. As explained with respect to Step 2A Prong Two, the computer readable medium executed by a computer system is at best the equivalent of merely adding the words apply it to the judicial exception. Mere instructions to apply an exception cannot provide an inventive concept. Moreover, the use of computer-implemented methods for indicating the efficacy of a treatment, including lung cancer, was well-known, understood and routine in the prior art. See Colpitts et al., US 2007/0178504, published 08/02/2007 (IDS submitted 12/13/2023). See also Yamka et al., US 2011/0183006 A1, published 07/28/2011 (“[0072] Another embodiment of the invention is a method of determining the efficacy of a treatment for osteoarthritis, comprising the steps of: (a) providing a biological sample from an animal affected by osteoarthritis, who has been subjected to said treatment, (b) determining the level in said sample of one or more biomarkers for osteoarthritis, to create an expression profile for said animal, and (c) comparing said expression profile with: i) a comparable expression profile obtained from said test animal before initiation of said treatment, and/or ii) a comparable expression profile obtained from said test animal at an earlier stage of said treatment, and/or iii) a comparable expression profile characteristic of a subject who is unaffected by osteoarthritis, wherein the one or more biomarkers for osteoarthritis, comprise expression products of one or more genes shown in Table 2 and/or Table 3.” “[0065] Yet another embodiment of the invention is a computer-implemented method for analyzing gene expression to screen for osteoarthritis comprising the steps of: i) compiling data comprising a plurality of measured gene expression signals derived from nucleic acid microarray analysis, selected from the group consisting of oligonucleotide microarray, c-DNA microarray, and focused gene chip analysis, or a combination thereof, of tissue samples into a form suitable for computer-based analysis: and ii) analyzing the compiled data, wherein the analyzing comprises identifying gene networks from a number of upregulated biomarker genes and down-regulated biomarker genes, wherein the biomarker genes are genes that have been identified as associating with presence or severity of osteoarthritis, said genes comprising genes listed in Table 2 and/or Table 3.“); Gold et al., US 2010/0070191 A1, published 03/18/2010 (“Claim 21. A computer-implemented method for indicating a likelihood of lung cancer, the method comprising: retrieving on a computer biomarker information for an individual, wherein the biomarker information comprises biomarker values that each correspond to one of at least N biomarkers selected from Table 1; performing with the computer a classification of each of said biomarker values; and indicating a likelihood that said individual has lung cancer based upon a plurality of classifications, and wherein N=2-61.” “[0184] The use of in vivo molecular biomarker imaging is increasing, including for clinical trials, for example, to more rapidly measure clinical efficacy in trials for new cancer therapies and/or to avoid prolonged treatment with a placebo for those diseases, such as multiple sclerosis, in which such prolonged treatment may be considered to be ethically questionable.”); and Wilcox et al., US 2013/0116150 A1, published 05/09/2013 (“Claim 19. A computer-implemented method for indicating a likelihood of lung cancer, the method comprising: retrieving on a computer biomarker information for an individual, wherein the biomarker information comprises biomarker values that each correspond to one of at least N biomarkers selected from Table 21; performing with the computer a classification of each of said biomarker values; and indicating a likelihood that said individual has lung cancer based upon a plurality of classifications, and wherein N=2-86.” “[0253] The use of in vivo molecular biomarker imaging is increasing, including for clinical trials, for example, to more rapidly measure clinical efficacy in trials for new cancer therapies and/or to avoid prolonged treatment with a placebo for those diseases, such as multiple sclerosis, in which such prolonged treatment may be considered to be ethically questionable.”). Moreover, when Claim 27, is considered as a whole, it does not improve the functioning of a computer, other technology, or technical field (MPEP 2106.04(d)(1) and 2106.05(a)); it does not apply the abstract idea to evaluate the efficacy of a particular treatment regimen in a patient diagnosed with lung cancer (MPEP 2106.04(d)(2)); it does not implement the abstract idea with, or in conjunction with, a particular machine (MPEP 2106.05(b)); it does not effect a transformation or reduction of a particular article to a different state or thing (MPEP 2106.05(c)); and it does not apply or use the abstract idea in some other meaningful way beyond linking the abstract idea to a particular field of use or technological environment (i.e., computer-assisted evaluation of the efficacy of a treatment; MPEP 2106.05(e) and 2106.05(h)). Claim 27 is not eligible.
With regard to Claims 28, 30-32, 35, 38 and 45, as admitted by Applicant at page 11-14 of the specification, the use of an assay chamber, such as a well of an assay plate, including commercially available an MSD® MULTI-ARRAY® 96-well plate and an MSD® plate reader, and electrochemiluminescent (ECL) label for conducting diagnostic tests is simply appending well-understood, routine, conventional activity previously known to the industry, specified at a high level of generality, to the judicial exception. Moreover, using calibrator proteins in immunoassays is well-understood, routine, conventional activity in the life science arts:
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Claims 28, 30-32, 35, 38 and 45 are not eligible.
With regard to Claim 33, recitations “a treatment regimen is administrated based on said evaluating step (c)”; “increasing or decreasing a dosage, frequency, or route of administration of a therapeutic agent of the treatment regimen”; “adding an additional therapeutic agent and/or palliative agent to the treatment regimen”; and “modifying the treatment regimen to eliminate one or more of the therapeutic and/or palliative agents,” respectively, do not provide any information as to how the patient is to be treated, or what the treatment is, but instead covers any possible treatment that a doctor decides to administer to the patient. In fact, these limitations are recited at such a high level of generality that it does not even require a doctor to take “at least four biomarkers” into account when deciding which treatment to administer, making the limitation's inclusion in the claim at best nominal. Like the claims in Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 78 (2012), Claim 33 here tells the relevant audience (doctors) about the law of nature and at most adds a suggestion that the doctors take this law into account when treating their patients. These limitations thus fail to meaningfully limit the claim because they do not require any particular application of the recited “at least four of biomarkers selected from the group consisting of NME-2, Flt-3L, MDC, KGF, P1GF, HGF, MCP1, SAT-1, MIP-1-b, GCLM, OPG, TNF RII, VEGF-D, ITAC, MMP-10, GPI, PPP2R4, AKR1B1, Amy1A, MIP-1b, P-Cadherin, and EPO, and combinations thereof,” and are at best the equivalent of merely adding the words "apply it” to the judicial exception. Accordingly, these limitations do not integrate the recited judicial exception into a practical application and the claim is therefore directed to the judicial exception. See MPEP 2106.05(f), which provides a detailed explanation and examples of how courts have evaluated the "mere instructions to apply an exception" consideration. Claim 33 is not eligible.
With regard to Claims 34 and 37, it is first noted that receiving information regarding a clinical symptom of the human subject and comparing a baseline level(s) of the panel of said biomarkers before said treatment regimen is initiated and during said treatment regimen is well-understood, routine, conventional activity in the life science arts because this is connected with the biomarker function to serve as a measurable substance in an organism whose presence is indicative of some phenomenon such as disease, infection, or environmental exposure. Second, “comparing” can be practically performed in the human mind, and thus falls into the “mental process” groupings of abstract ideas. Claims 34 and 37 are not eligible.
With regard to Claim 36, as admitted by Applicant at pages 12-13 of the specification, conducting a multiplexed assay measurement of a plurality of biomarkers in a test sample, wherein the multiplexed assay measurement is conducted using one reaction volume comprising the test sample is simply appending well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception. Claim 36 is not eligible.
With regard to Claims 40-42, it is first noted that the courts have recognized determining the level of a biomarker in blood by any means, as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity. Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017). See MPEP 2106.05(d) “Well-Understood, Routine, Conventional Activity.” Second, as discussed above, a multiplexed assay measurement of at least four biomarkers in a test sample is simply appending well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception. Claims 40-42 are not eligible.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) 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 27, 28, 30-38, 40-42 and 45 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Colpitts et al., US 2007/0178504, published 08/02/2007 (IDS submitted 12/13/2023), in view of Mathew et al., US 2009/0075299 A1, published 03/19/2009; Nakamura et al., US 2011/0152345 A1, published 06/23/2011; Product Insert “MSD® 96-Well and MULTI-SPOT® Human Cytokine Assays: Base Kit,” dated Oct 2009; Glezer et al., U.S. Patent 7,981,362, issued 07/19/2011 (IDS submitted 12/13/2023); prior publication data US 2005/0142033 A1, June 30, 2005; in view of the prior art cited in the instant disclosure; Ó’Fágáin C. (2004) “Lyophilization of Proteins.” In: Cutler P. (eds) Protein Purification Protocols. Methods in Molecular Biology, vol. 244, Humana Press, pp. 309-321 (IDS submitted 12/13/2023); Saffar et al., “Expression of Galectin-3, nm-23, and Cyclooxygenase-2 Could Potentially Discriminate Between Benign and Malignant Pheochromocytoma,” Am. J. Clin. Pathol., 2011, vol. 135, pp. 454-460 (IDS submitted 12/13/2023); Yamayoshi et al., “Expression of keratinocyte growth factor/fibroblast growth factor-7 and its receptor in human lung cancer: correlation with tumour proliferative activity and patient prognosis,” J. Pathol., 2004, vol. 204, pp. 110-118 (IDS submitted 12/13/2023); Nakanishi et al., “Expression of macrophage-derived chemokine (MDC)/CCL22 in human lung cancer,” Cancer Immunol. Immunotherapy, 2006, vol. 55, issue 11, pp. 1320-1329 (IDS submitted 12/13/2023); and Streeper et al., WO 2012/149550 A1, published 11/01/2012.
Colpitts et al. teach a computer-implemented method for evaluating the efficacy of a treatment regimen in a patient diagnosed with lung cancer by employing a multiplexed immunoassay to measure a level of two or biomarkers in lung cancer patient samples, such as serum, the elected species (b), and comparing said level to normal control level of these biomarkers, wherein an aliquot of sample suspected of containing one or more of the analytes is placed in an incubation well, the elected species (a), using a kit comprising reagents containing at least one antibody for quantifying one or more antigens in a test sample, wherein said antigens are cytokeratin 19, cytokeratin 18, CA 19-9, CEA, CA15-3, CA125, SCC and ProGRP; and one or more algorithms or computer programs for performing the steps of combining and comparing the amount of each antigen quantified in the test sample:
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Emphasis added.
Colpitts et al. do not specifically teach:
(1) evaluating responsiveness of a patient to a treatment regimen based on comparing the biomarker levels, as recited in Claim 27; and adjusting the treatment regimen based on this evaluating, as recited in Claim 33;
(2) the wells comprising at least four discrete binding domains to which capture antibodies to human analytes are bound, as recited in Claim 30, wherein said discrete binding domains are positioned on an electrode within said well, as recited in Claim 32; and an MSD® MULTI-ARRAY® 96-well plate and an MSD® plate reader, recited in Claim 35;
(3) detection antibodies labeled with an electrochemiluminescent (ECL) label, as recited in Claim 31;
(4) calibrator proteins, as recited in Claim 28; and
(5) MDC, NME-2, KGF and PIGF as 4 biomarkers as biomarkers of the elected species (d).
Regarding (1), Mathew et al., throughout the publication, and, for example, in Abstract, teach methods of diagnosing cancerous conditions in a patient, as well as methods of monitoring the progression of a cancerous condition and/or methods of monitoring a treatment protocol of a therapeutic agent or a chemotherapeutic regimen. In paragraphs [0009] and [0022], Mathew et al. teach a method for evaluating the efficacy of a cancer therapeutic agent or treatment regimen based on comparing the biomarker levels and using a detection cut-off level:
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Emphasis added.
In Claim 11, Mathew et al. teach measuring the level(s) of a biomarker in samples obtained from a patient at different times:
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In Claim 13, Mathew et al. teach comparing the level of the biomarker in the sample to a level of the biomarker in a normal control sample. Although Mathew et al. do not specifically measuring a baseline level(s) of a biomarker before a treatment regimen is initiated and measuring an interim level of said biomarker during said treatment regimen, as evidenced by Nakamura et al., determining the biomarker level before and after therapy is a common practice in monitoring treatment or assessing the efficacy of a therapy for an individual diagnosed with lung cancer:
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Emphasis added.
With regard to (2) and the elected species (a), in paragraph [0041], Mathew et al. teach:
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As evidenced by Product Insert, MSD® 96-Well and MULTI-SPOT® plates provide at least four discrete binding domains, which are in the form of a spot pattern:
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With regard to (1), in paragraph [0025], Mathew et al. teach adjusting the treatment regimen and additional therapeutic agents and/or palliative agents:
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Emphasis added.
Regarding (2)-(4), Glezer et al., throughout the patent, and, for example, in Claims 13-33, teach a kit comprising a multi-well assay plate, wherein a binding reagent is immobilized on a working electrode within a well; see Claims 26 and 33. In Col. 142, line 8, through Col. 143, line 3, Glezer et al. teach multi-analyte immunoassays in multi-well assay plates using detection antibodies labeled with an electrochemiluminescent (ECL) label, wherein four capture antibodies (each selective for one of the analytes of interest) were patterned into distinct assay domains by microdispensing solutions of the antibodies on the fluid containment regions within each well (one antibody per region) and allowing the antibodies to adsorb to the surface of the working electrode. As admitted by Applicant at pages 13-14 of the instant disclosure, a multi-well assay plate, taught by this prior art references can be configured to measure a level of a plurality of the recited biomarkers in a patient sample:
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In Col. 123, line 12, Glezer et al. teach the use of calibrators. Although Glezer et al. do not specifically teach a lyophilized blend as a set of calibrator proteins, as evidenced by Ó’Fágáin, lyophilization, or freeze-drying, is a well-known method for the preservation of labile materials, such as proteins, in a dehydrated form, and, since the protein will preserve all or most of its initial biological activity in the dry state, this offers many advantages for long-term storage of the protein in question.
With regard to the elected species (c), the Examiner notes that the use of Capillary Isoelectric Focusing (CLEF) is a well-known analytical testing method in the prior art:
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Regarding (5) and the elected species (d), Nakanishi et al., throughout the publication, and, for example, in Abstract, teach involvement of macrophage-derived chemokine (MDC) in a human lung cancer such as squamous cell carcinoma and adenocarcinoma, which are NSCLC as stated in paragraph [0043] of US 2020/0158731 A1, and its potential as a predictive marker for improving the prognosis of lung cancer.
Regarding (5) and the elected species (d), Yamayoshi et al., throughout the publication, and, for example, at page 117, last paragraph, teach involvement of keratinocyte growth factor (KGF) in a human lung cancer and its pivotal role in the regulation of lung cancer cell kinetics. In Abstract, Yamayoshi et al. teach the use of KGF and its receptor in human lung cancer patient prognosis.
Regarding (5) and the elected species (d), Streeper et al., throughout the publication, and, for example, in Claims 23, 24 and 27 at page 71, teach Placenta Growth Factor ("PIGF") as a biomarker of lung disease, such as non-small cell lung cancer.
Regarding (5) and the elected species (d), Saffar et al., throughout the publication, and, for example, at page 457, right column, teach that it is known in the art that nm-23 (also known as NME-2) is involved in non-small cell carcinoma of lung:
“Different genes involved in different stages of the cell cycle, induction of cell differentiation, adhesion, or apoptosis have been evaluated regarding their potential for prediction of the course of neoplastic lesions and have sometimes proved useful. Expression of nm-23, a metastasis suppressor gene,7 is variable depending on the state of cell growth; highest and lowest nm-23 expression occur in the S phase and in the G0/G1 phase, respectively.8 Decreased expression of this gene in different cancers, including breast carcinoma,9–11 hepatocellular carcinoma,12,13 non–small cell carcinoma of lung,14–16 ovarian carcinoma,17,18 bladder carcinoma,19,20 and renal cell carcinoma,21 has been associated with an increase in tumor invasiveness and prevalence of metastasis. A study by Ohta et al7 on 15 benign and 10 malignant pheochromocytomas showed that down-regulation of the nm-23 gene evaluated by real-time polymerase chain reaction was significantly higher in malignant tumors. Our study also demonstrated a greater extent of immunoreactivity for nm-23 in benign pheochromocytomas compared with the malignant group, the difference being statistically significant (P = .000).” Emphasis added.
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According to MPEP 2144.06, “Combining equivalents known for the same purpose,”
"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); and Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious). Emphasis added.
It would have been prima facie obvious, at the time the invention was made, for one of ordinary skill in the art to have included a measurement a level of a biomarker panel comprising MDC, NME-2, KGF and PIGF in a patient sample in the method, taught by combination of Colpitts et al., Mathew et al., Nakamura et al. and Glezer et al., because each of MDC, NME-2, KGF and PIGF is involved in lung cancer, as taught by Nakanishi et al., Saffar et al., Yamayoshi et al. and Streeper et al., respectively, and, accordingly, may be used to help guide treatment decisions for targeted therapy.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GALINA M YAKOVLEVA whose telephone number is (571)270-3282. The examiner can normally be reached on M-F 8:30 AM-5:00 PM.
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/GALINA M. YAKOVLEVA/Primary Examiner, Art Unit 1678