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 .
Status of Application, Amendments, And/Or Claims
The Applicants amendments/remarks received 12/23/2025 are acknowledged. Claims 1-16 are amended; no claims are canceled; no claims are withdrawn; claims 1-16 are pending and have been examined on the merits.
Drawings
The replacement drawings received 12/23/2025 are accepted.
Claim Objections
The objection to claims 1, 5-7 and 15-16, as set forth at pp. 4-5 of the previous Office Action, is withdrawn in view of the amendment of the claims.
Claim Rejections - 35 USC § 101
The rejection of claims 7-8, 10-11 and 13 under 35 U.S.C. § 101 as set forth at pp. 5-9 of the previous Office Action, is withdrawn in view of the amendment of the claims.
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 1-6 and 15-16 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception without significantly more.
Claims 1-6 and 15-16 are drawn to methods comprising a mental step, i.e., a judicial exception.
The first question in the subject matter eligibility determination is “Is the claim to a process, machine, manufacture or composition of matter?” (Step 1)
Yes, claims 1-6 and 15-16 are drawn to methods, i.e., a process.
The second question (Step 2A, prong 1) in the subject matter eligibility determination asks “Is the claim directed to a law of nature, a natural phenomenon, or an abstract idea (judicially recognized exceptions)?"
Yes, the claimed processes are drawn to processes comprising an abstract idea (mental step; judicial exception) and well understood, conventional and routine laboratory steps.
Regarding claims 1-6, the processes are drawn to contacting enolase 1 (ENO1), or a derivative, a precursor, a mutant, or a functional fragment thereof, comprising the amino acid sequence according to SEQ ID NO: 1, or an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 1; at least one nucleic acid; and a candidate compound; and detecting and/or quantifying a binding between the enzyme and nucleic acid and determining whether the candidate compound is suitable for the prevention and/or treatment of a proliferative disease based on the differential level of the binding between the ENO1 and the at least one nucleic acid contacted with the candidate compound compared to the binding between the ENO1 and the at least one nucleic acid not contacted with the candidate compound, i.e., a mental step, which is an abstract idea or intangible relationship, which is a judicial exception.
Regarding claim 15, the process is drawn to contacting enolase 1 (ENO1), or a derivative, a precursor, a mutant, or a functional fragment thereof, comprising the amino acid sequence according to SEQ ID NO: 1, or an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 1; at least one nucleic acid; and a candidate compound; detecting and/or quantifying a modification of the enzyme and determining whether the candidate compound is suitable for prevention and/or treatment of a disease based on the differential level of the modification in the ENO1 contacted with the candidate compound compared to the at least one modification in the ENO1 not contacted with the candidate compound, i.e., a mental step, which is an abstract idea or intangible relationship, which is a judicial exception.
Regarding claim 16, the process is drawn to contacting enolase 1 (ENO1), or a derivative, a precursor, a mutant, or a functional fragment thereof, comprising the amino acid sequence according to SEQ ID NO: 1, or an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 1; and at least one nucleic acid; quantifying the binding between the ENO1e and the nucleic acid and determining a diagnosis, prognosis, stratification and/or monitoring of a therapy, of a proliferative disease in the subject based on the differential level of binding between the ENO1 and the nucleic acid in the sample from the subject compared to a control or reference value, i.e., a mental step, which is an abstract idea or intangible relationship, which is a judicial exception.
Step 2A, prong 2 asks “Does the claim recite additional elements that integrate the judicial exception into a practical application?”
Regarding claims 1-6 and 15-16, no, the claims do not integrate the judicial exception into a practical application because the claims do not recite any practical steps to be taken upon making the mental step of whether the candidate compound is suitable for the prevention and/or treatment of the disease or the mental step of determining a diagnosis, prognosis, stratification and/or monitoring of a therapy, of the disease in the subject.
The final question (Step 2B) in the subject matter eligibility determination to be asked is “Does the claim recite additional elements that amount to significantly more than the judicial exception?”
No, claims 1-6 and 15-16 do not recite additional elements that amount to significantly more than the judicial exception.
Regarding claims 1-6 and 16, the contacting of the enzyme and the nucleic acid or the contacting of the enzyme, the nucleic acid and a candidate compound and measuring the binding between the enzyme and the nucleic acid is well-understood, routine and conventional as disclosed in Austin et al., US 2006/0051744 (cite A, PTO-892, 9/23/2025), published over 14 years before the effective filing date of the instant invention.
Regarding claim 15, the contacting of the enzyme and the nucleic acid and measuring modifications of the enzyme, such as citrullination, is well-understood, routine and conventional as disclosed in Durrant et al., US 2018/0207291 (cite B, PTO-892, 9/23/2025) , published over 2 years before the effective filing date of the instant invention.
These well-understood, routine, conventional activities are not part of a specific transformative method, but rather represent generalized method steps which are executed solely for the production of data for the mental step. Accordingly, claims 1-6 and 15-16 do not amount to significantly more than the judicial exceptions and are not patent eligible.
Thus, claims 1-6 and 15-16 are rejected under U.S.C. 101 as not being drawn to patent eligible subject matter.
Response to Arguments
Applicant's arguments filed 12/23/2025 have been fully considered but they are not persuasive. Arguments of the Applicant’s Response on pp. 11-13 and 16-22 regarding the claim objections; rejections under 35 U.S.C. §§ 112(a), 112(b), 102(a)(1) and 102(a)(1)/(a)(2); and the rejection of claims 7-8, 10-11 and 13 under 35 U.S.C. § 101 are moot as the rejections have been withdrawn.
Regarding the rejection of claims 1-6 and 15-16 under 35 U.S.C. § 101, Applicant argues that claim 1 is directed to a process (p. 13, ¶4-5). Yes, claims 1-6 and 15-16 are directed to processes as stated in the rejection in the previous Office action and above.
Applicant argues that claim 1 (and also applied to claims 15 and 16 on p. 15) “is not directed to a mathematical concept, a method of organizing human activity, or a mental process” (p. 14, ¶1). This is incorrect. Determining whether the candidate compound is suitable for the prevention and/or treatment of a proliferative disease based on the differential level of the binding between the ENO1 and the at least one nucleic acid contacted with the candidate compound compared to the binding between the ENO1 and the at least one nucleic acid not contacted with the candidate compound is clearly a mental step, which is an abstract idea or intangible relationship, which is a judicial exception.
Hence, Applicant’s allegation (p. 14, last ¶) that “the claim is not "directed to" a judicial exception and is patent-eligible without further analysis” is completely unpersuasive.
Applicant argues that the additional elements, individually and in ordered combination, are not well-understood, routine, or conventional in the field (p. 15, ¶2). This is unpersuasive as all the process steps are disclosed in Austin et al., US 2006/0051744 (cite A, PTO-892, 9/23/2025), published over 14 years before the effective filing date of the instant invention at [0027], [0124-128] and [0176].
Asserting that the additional elements, individually and in ordered combination, are not well-understood, routine, or conventional in the field, Applicant argues (p. 15, ¶2) that “First, the claim is limited to a structurally defined ENO1 polypeptide, i.e., SEQ ID NO:1 and sequences having at least 80% identity (including derivatives, precursors, mutants, and functional fragments), rather than any generic enzyme or protein. This structural limitation reflects a specific technical choice by the inventors and is not a routine, off-the-shelf reagent use. Second, the claim recites a particular ordered combination of steps: (a) providing the defined ENO1 enzyme, at least one nucleic acid, and a candidate compound; (b) bringing them into contact; and (c) detecting and/or quantifying binding...” This is completely unpersuasive as Austin discloses a method comprising (a) providing feline alpha-enolase, i.e., SEQ ID NO: 10 which is 96% identical to instant SEQ ID NO: 1 ([0052-53]; Figs. 7-8); multi-organ CoV RNA, i.e., at least one nucleic acid; and a candidate compound; (b) bringing into contact the at least one enzyme of the glycolytic pathway, the at least one nucleic acid and the candidate compound; (c) detecting and/or quantifying a binding between the at least one enzyme of the glycolytic pathway and the at least one nucleic acid; wherein a differential level of the binding between the at least one enzyme of the glycolytic pathway and the at least one nucleic acid contacted with the candidate compound compared to the binding between the at least one enzyme of the glycolytic pathway and the at least one nucleic acid not contacted with the candidate compound indicates the candidate compound as suitable for the prevention and/or treatment of the disease ([0027], [0124-128], [0176]).
Hence, the additional elements, individually and in ordered combination, are CLEARLY well-understood, routine, or conventional in the field as they were taught by Austin 14 years before the priority document of the instant application.
Applicant’s allegation that claims 1-6 and 15-16 are patent eligible subject matter and should not be rejected under 35 U.S.C. 101 is unpersuasive; hence, the rejection is maintained with modification to address the claim amendments and for clarity.
Claim Rejections - 35 USC § 112
The rejection of claims 1-6 and 15-16 under 35 U.S.C. § 112(a), as set forth at pp. 12-15 of the previous Office Action, is withdrawn, in view of the amendment of the claims.
The rejection of claims 1-16 under 35 U.S.C. § 112(b), as set forth at pp. 15-24 of the previous Office Action, is withdrawn in view of the amendment of the claims.
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 15-16 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 15 recites the limitation "the at least one nucleic acid" in line 10. There is insufficient antecedent basis for this limitation in the claim. Claim 15 does not previously recite a nucleic acid; hence, the limitation lacks antecedent basis. Appropriate correction is required.
Claim 15 recites the limitation "the at engineered least one enzyme of the glycolytic pathway" in line 15. There is insufficient antecedent basis for this limitation in the claim. Claim 15 does not previously recite at engineered least one enzyme of the glycolytic pathway; hence, the limitation lacks antecedent basis. Appropriate correction is required.
Claim 15 recites the limitation "the engineered at least one modification" in lines 17-18. There is insufficient antecedent basis for this limitation in the claim. Claim 15 does not previously recite an engineered at least one modification; hence, the limitation lacks antecedent basis. Appropriate correction is required.
Regarding claim 16, the phrase "wherein engineered the at least one enzyme of the glycolytic pathway is enolase 1", in lines 5-6, renders the claim indefinite because it appears to recite that the enzyme is not enolase 1 until engineered which is not disclosed by the original disclosure; hence, it is unclear what the metes and bounds of the limitation is.
NOTE: Amending the phrase to "wherein engineered at least one enzyme of the glycolytic pathway is enolase 1" would overcome the indefiniteness rejection of the limitation at lines 5-6 of claim 16.
The following is a quotation of the first paragraph 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 the first paragraph of pre-AIA 35 U.S.C. 112:
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.
Claims 1-6 and 15-16 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 claims contain 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.
The original disclosure does not disclose that the enolase in the method of claim 1 is engineered; hence, claim 1 constitutes new matter. Claims 2-6 depend from claim 1; thus, claims 2-6 also constitute new matter.
Claim 15 recites that the modification to the enzyme is engineered at lines 17-18. The original disclosure DOES NOT disclose that the modification to the enzyme is an engineered modification; hence, the limitation, and thus the claim, constitutes new matter.
Claim 16 recites “(a) engineering at least one enzyme of a glycolytic pathway; (b) providing a sample comprising the engineered at least one enzyme of the glycolytic pathway from the subject” at lines 3-5; however, the original disclosure DOES NOT disclose that the enolase in patient samples is engineered. For the enolase in the patient sample to be engineered, the patient would have to be genetically engineered to express an engineered enolase. The original disclosure DOES NOT disclose that the patients in claim 16 have been previously genetically engineered; hence, the claim constitutes new matter.
Claim Rejections - 35 USC § 102
The rejection of claims 7-8 and 11-13 under 35 U.S.C. 102(a)(1) over Sakimura et al., 1985 (cite U, PTO-892, 9/23/2025; herein “Sakimura”) in light of “SEQ 1 (Query) aligned to Sakimura rat non-neuronal enolase (Sbjct)” (cite W, PTO-892, 9/23/2025) as set forth at pp. 24-26 of the previous Office Action, is withdrawn in view of the amendment of the claims.
The rejection of claims 7-8 and 10-12 under 35 U.S.C. 102(a)(1) over Mannen et al., 1999 (cite V, PTO-892, 9/23/2025; herein “Mannen”) in light of GenBank AF072588 (cite X, PTO-892, 9/23/2025; herein “AF072588”) and “SEQ 1 (Query) aligned to Mannen T scripta enolase (Sbjct)” (p. 2, cite U, PTO-892, 9/23/2025 as set forth at pp. 26-27 of the previous Office Action, is withdrawn in view of the amendment of the claims.
The rejection of claims 1-6 and 16 under 35 U.S.C. 102(a)(1)/(a)(2) over Austin et al., US 2006/0051744 (cite A, PTO-892, 9/23/2025; herein “Austin”) in light of “SEQ 1 (Query) aligned to Austin feline enolase (Sbjct)” (p. 2, cite V, PTO-892, 9/23/2025) as set forth at pp. 27-28 of the previous Office Action, is withdrawn in view of the amendment of the claims.
The rejection of claims 7, 11 and 13-14 under 35 U.S.C. 102(a)(1)/102(a)(2) over Durrant et al., US 2018/0207291 (cite B, PTO-892, 9/23/2025; herein “Durrant”) as set forth at p. 29 of the previous Office Action, is withdrawn in view of the amendment of the claims.
Claim Rejections - 35 USC § 103
The rejection of claims 7, 11 and 13-15 under 35 U.S.C. § 103(a) over Durrant et al., US 2018/0207291 (cite B, PTO-892, 9/23/2025; herein “Durrant”) as set forth at pp. 29-31 of the previous Office Action, is withdrawn in view of the amendment of the claims.
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 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-6 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Miller et al., US 2011/0213019 (cite A, attached PTO-892; herein “Miller”) in view of Austin et al., US 2006/0051744 (cite A, PTO-892, 9/23/2025; herein “Austin”).
Miller discloses that alpha-enolase forms complexes with a specific nucleic acid structure, G-rich quadruplex forming oligonucleotides, in the c-myc promoter which specifically binds alpha-enolase, i.e., supershift of the alpha-enolase-nucleic acid complex with anti-enolase antibodies; that alpha-enolase completes with MBP-1 at the c-myc promoter and likely plays an important role in regulation of cellular proliferation [0087-89]. Miller teaches that the patient can be a human [0035]; hence, a person of ordinary skill in the art at the time of filing would have found it obvious for the alpha-enolase to be human enolase, i.e., 100% identical to instant SEQ ID NO: 1.
Miller discloses that many cancer-related genes have quadruplex forming sequences in their G-rich promoter regions [0003]; that G-rich quadruplex forming oligonucleotides are useful in inhibiting cellular growth and proliferation, treating cancer, and inhibiting telomerase activity [0007]; and teaches treating cancer by administering quadruplex forming oligonucleotides ([0010], claims 12, 16).
Miller does not specifically teach screening for compounds, such as other quadruplex oligonucleotides, which inhibit or enhance the binding of human alpha-enolase with the G-rich quadruplex forming nucleic acid from the c-myc promoter; however, a person of ordinary skill in the art at the time of filing would have found it obvious to screen for such compounds in order to use the compounds to treat patients with a proliferative disease, such as cancer, in view of the disclosure of Austin.
Austin discloses a method for identifying a compound suitable for the prevention and/or treatment of a disease (multi-organ CoV infection), the method comprising the steps of: (a) providing feline alpha-enolase, i.e., SEQ ID NO: 10 which is 96% identical to instant SEQ ID NO: 1 ([0052-53]; Figs. 7-8); multi-organ CoV RNA, i.e., at least one nucleic acid; and a candidate compound; (b) bringing into contact the at least one enzyme of the glycolytic pathway, the at least one nucleic acid and the candidate compound; (c) detecting and/or quantifying a binding between the at least one enzyme of the glycolytic pathway and the at least one nucleic acid; wherein a differential level of the binding between the at least one enzyme of the glycolytic pathway and the at least one nucleic acid contacted with the candidate compound compared to the binding between the at least one enzyme of the glycolytic pathway and the at least one nucleic acid not contacted with the candidate compound indicates the candidate compound as suitable for the prevention and/or treatment of the disease ([0027], [0124-128], [0176]).
Austin discloses that the enolase - RNA complex can be from samples, i.e., subject sera, bodily fluids or organs [0108].
Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to contact human alpha-enolase, i.e., at least one enzyme of the glycolytic pathway wherein the at least one enzyme of the glycolytic pathway is enolase 1 (ENO1) comprising the amino acid sequence according to SEQ ID NO: 1, whether from a patient sample or generated in the laboratory, i.e., engineered; with the G-rich quadruplex sequence from the c-myc promoter, i.e., at least one nucleic acid and a candidate compound, such as variant quadruplex oligonucleotides; quantifying the binding between the human alpha-enolase and the G-rich quadruplex sequence from the c-myc promoter in the presence and the absence of the test compound and determine whether the candidate compound suitable for the treatment of a proliferative disease, such as cancer because Miller documents that alpha-enolase binds the G-rich quadruplex sequence from the c-myc promoter and likely plays a role in proliferation and Austin discloses methods for screening for test compounds which can modify a bimolecular interaction; therefore, claims 1-6 are prima facie obvious.
Likewise, the disclosures of Miller and Austin make obvious a method of detecting binding between enolase from a patient’s sample and the G-rich quadruplex sequence from the c-myc promoter, i.e., at least one nucleic acid, and comparing the binding to that seen with reference enolase to determine if the proliferative disorder of the patient is associated with a mutation in the patient’s enolase gene, i.e., wherein a differential level of the binding between the engineered at least one enzyme of the glycolytic pathway and the at least one nucleic acid in the sample from the subject as detected and/or quantified in step (d) compared to a control or reference value is indicative for the diagnosis, prognosis, stratification and/or monitoring of a therapy, of the disease in the subject, wherein the disease is a proliferative disease; therefore, claim 16 is prima facie obvious.
Allowable Subject Matter
Claims 7-14 are allowed.
Conclusion
Claims 7-14 are allowed. Claims 1-6 and 15-16 are rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Trent R Clarke whose telephone number is (571)272-2904. The examiner can normally be reached M-F 10-7 MST.
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/TRENT R CLARKE/ Examiner, Art Unit 1651
/DAVID W BERKE-SCHLESSEL/ Primary Examiner, Art Unit 1651
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