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 .
Response to Amendment
The Amendment filed 03/30/2026 in which claims 15, 16, 18, 21 were amended, and claims 19, 20 and 22 were canceled, has been entered.
Claims 15-18, 21 are currently under examination on the merits.
Drawings
(Previous objection, withdrawn) Applicant’s amendments to the Drawings have overcome the objection previously set forth in the Non-Final Office Action mailed on 12/29/2025.
Specification
(Previous objection, withdrawn) Applicant’s amendments to the Specification have overcome the objection previously set forth in the Non-Final Office Action mailed on 12/29/2025.
Nucleotide and/or Amino Acid Sequence Disclosures
(Previous objection, withdrawn) Applicant’s amendments to the Specification concerning nucleotide and/or amino acid sequence disclosures have overcome the objection previously set forth in the Non-Final Office Action mailed on 12/29/2025.
Claim Objections
(Previous objections, withdrawn as to claims 16, 18) Applicant’s amendments to claims 16, 18 have overcome previous objections to those claims.
Claim Rejections - 35 USC § 112(b)
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.
(Previous objections, withdrawn as to claim 20) Claim 20 was rejected on the basis that it contains an improper Markush grouping of alternatives.
The previous rejections of claim 20 is moot in view of Applicant’s cancelation of this claim.
(Previous objections, maintained and modified as necessitated by amendment as to claim 16) Claims 16 is 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.
Amended claim 16 recites “wherein the SREBP2 protein consists of the amino acid sequence of SEQ ID NO: 1.” This recitation is unclear because the sequence in SEQ ID NO: 1, as originally filed, is an artificial sequence (see instant sequence listing) and would not be present in human cells in a sample. It is herein noted that Applicant filed on 03/30/2026 a new amino sequence for SEQ ID NO: 1 which is different from the one originally filed (see also rejections under 35 USC § 112(a) – Written Description below). Instant Specification (page 7) notes that SEQ ID NO: 1, as originally filed, is a full length sequence for the SREBP2 protein. Upon sequence alignment of SEQ ID NO: 1, as originally filed, with a consensus sequence for the SREBP2 protein (GenBank accession number NP 004590.1) it is noted that SEQ ID NO: 1, as originally filed, differs from the consensus full length sequence for the human SREBP2 protein in that SEQ ID NO: 1, as originally filed, bears a deletion of amino acids 462-487 (see alignment of record), and thus it is unclear why an amino acid sequence consisting of SEQ ID NO: 1, as originally filed, would be found in a sample comprising human cells. It is noted that the transitional phrase “consisting of” excludes any element not specified in the claim. See MPEP 2111.03. Therefore, the claim is indefinite. For purposes of compact prosecution and applying prior art, claim 16 was interpreted herein as referring to a SREBP2 protein consisting of the amino acid sequence of the human SREBP2.
Claim Rejections - 35 USC § 112(a) – Written Description
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.
(New rejection, necessitated by amendment as to claims 16) Claim 16 is 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
M.P.E.P. § 2163 recites, “An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. . . . One must define a compound by ‘whatever characteristics sufficiently distinguish it.’ A lack of adequate written description issue also arises if the knowledge and level of skill in the art would not permit one skilled in the art to immediately envisage the product claimed from the disclosed process.” Furthermore, § 2163 notes, “While there is no in haec verba requirement, newly added claim limitations must be supported in the specification through express, implicit, or inherent disclosure.” When such disclosure is absent, the newly added claim limitations introduce new matter.
Claim 16 has been amended to require the SREBP2 protein consisting of the amino acid sequence of SEQ ID NO: 1. It is noted that a new Sequence Listing has been submitted on 03/30/2026 in which Applicant has allegedly updated SEQ ID NO: 1 in accordance to GenBank No. NP 004590.2. As previously noted, the newly submitted sequence differs from the originally filed SEQ ID NO: 1 in that the originally filed SEQ ID NO: 1 bears a deletion of amino acids 462-487. Neither Specification nor the claims as previously submitted on 02/17/2023 describe the newly submitted SEQ ID NO: 1 (GenBank No. NP 004590.2) as the SREBP2 required by the instantly claimed method. Thus, the new sequence constitutes new matter.
Therefore, the new amino acid sequence for SEQ ID NO: 1 lacks descriptive support in the Specification. Since no basis has been found to support the new sequence in the Specification, claim 16 are rejected as incorporating new matter.
Claim Rejections - 35 USC § 112(a) – Enablement
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.
(Previous rejection, withdrawn as to claims 19-20 and 22, maintained and modified as necessitated by amendment as to claims 15-18, 21) Claims 15-18, 21 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of measuring protein or mRNA levels of SRBP2 in a sample and comparing such levels to control standards, it does not reasonably provide enablement for any method for diagnosing specifically sepsis or septic shock, and treating sepsis or septic shock. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
See claims 15-18, 21 submitted on 03/30/2026.
The previous rejections of claims 19, 20 and 22 are moot in view of Applicant’s cancelation of these claims.
In making a determination as to whether an application has met the requirements for enablement under 35 U.S.C. 112 P1, the courts have put forth a series of factors. See, In re Wands, 8 USPQ2d 1400, at 1404 (CAFC 1988). The factors considered include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. Id. While it is not essential that every factor be examined in detail, those factors deemed most relevant should be considered. In the present case, the factors deemed relevant are those of: the breadth of the claims, the state of the art, the absence of working examples, and the quantity of experimentation necessary.
Nature of the invention and breadth of the claims: Amended claims 15-18, 21 are drawn to a method for diagnosing and treating sepsis or a septic shock comprising the steps of: (a) measuring the expression levels of SREBP2 protein or mRNA in a sample; (b) comparing the expression levels of the SREBP2 protein or mRNA in the sample with that of a normal subject; (c) diagnosing with sepsis or septic shock; (d) and treating the subject diagnosed with sepsis or septic shock by administering a standard therapy.
State of the art and the unpredictability of the art: The state of the art acknowledges many methods of diagnosing a disease or condition or syndrome wherein a biomarker is measured by known methods in the art (see Yuan et al. 2019. Cited in Applicant’s IDS submitted on 01/17/2023). However, levels of SREBP2 protein or mRNA in a sample have been associated with a wide range of diseases, conditions, and syndromes. For example, Lee et al. (US PGPub 20210190799 A1 to Lee et al. filed on 10/26/2018. See PTO-892: Notice of References Cited.) teach that levels of SREBP2 protein or mRNA in a sample are associated with many types of liver disease some of which are caused by infectious agents such as hepatitis and some not caused by infectious agents such as alcoholic liver disease, drug toxic liver disease, autoimmune liver disease, etc. (¶¶ [0001]-[0007]). Further, Lee et al. teach that levels of SREBP2 protein or mRNA in a sample are associated with inflammation in general, which can result from infectious diseases as well as non-infectious conditions (¶¶ [0007]-[0016]). It is noted that instant Specification describes ‘sepsis’ as a systemic inflammatory response that appears as a complication of an infectious disease which can develop into a ‘septic shock’ (page 14).
While the instant claims read on sepsis and septic shock, the prior art teaches a correlation of levels of SREBP2 protein or mRNA in a sample with general inflammation which can arise from a broader genus of diseases and conditions. In other words, based on the teachings of the prior art, the claimed method for diagnosing comprising assessing levels of SREBP2 protein or mRNA in a sample and comparing those levels to control standards, could diagnose a wide range of conditions associated with inflammation which can induce a change in SREBP2 protein or mRNA levels in a subject. Moreover, to diagnose sepsis and or a septic shock specifically, a method would need to be capable of distinguishing between the root cause of the inflammatory response (a complication of an infectious disease) from internal/lifestyle factors associated with non-infectious conditions in a subject.
Furthermore, even if the claimed method would be capable of diagnosing sepsis or a septic shock, treating sepsis or a septic shock has a higher clinical benchmark. It is noted that while the instant claims read on sepsis and or a septic shock resulting from any complication.
To summarize, the state of the art does not provide any evidence of or predictability for diagnosing sepsis or a septic shock by assessing levels of SREBP2 protein and mRNA and treatment therapies for sepsis or a septic shock as encompassed by instant claims.
The amount of direction and the working examples provided: the instant application does not provide any working examples of a method for diagnosing sepsis or a septic shock comprising distinguishing sepsis or a septic shock as a complication of an infectious disease from a non-infectious disease and treating sepsis or a septic shock with the claimed method. The instant application provides three examples (pages 25-28) to demonstrate the following: 1) SREBP2 is activated in PBMCs of patients with SARS-CoV-2 infection; 2) expression levels of SREBP2 are correlated with hyperinflammation in lung tissues of patients with SARS-CoV-2 infection; and 3) expression of the C-terminal of the human SREBP2 is correlated with vascular development in culture cells. No working examples are provided that suggest or imply diagnosing specifically sepsis or a septic shock as a complication of an infectious disease and/or treating sepsis or a septic shock by administering a standard therapy.
Quantity of experimentation necessary: As discussed above undue experimentation would be required to practice the claimed invention commensurate with the scope of the claims. Reasonable correlation must exist between the scope of the claims and scope of enablement set forth. In view of the quantity of experimentation necessary, the absence of working examples, the unpredictability of the art, the lack of sufficient guidance in specification, and the breadth of the claims, it would take undue trials and errors to practice the claimed invention.
In view of the foregoing, the Specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
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.
(Previous rejection, withdrawn as to claims 19-20 and 22, maintained and modified as necessitated by amendment as to claims 15-18, 21) Claims 15-18, 21 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more. This judicial exception is not integrated into a practical application and the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons set forth below.
See claims 15-18, 21 submitted on 03/30/2026.
The previous rejections of claims 19, 20 and 22 are moot in view of Applicant’s cancelation of these claims.
These claims are analyzed for eligibility in accordance with their broadest reasonable interpretation. In view of the Subject Matter Eligibility Test for Products and Processes and the Steps cited below (See flowchart at pages 10-11 at https://www.uspto.gov/sites/default/files/documents/peg_oct_2019_update.pdf ).
The claims are directed to a process, which is one of the four statutory categories of invention (Step 1: YES).
The amended claims are directed to the natural correlation between the mRNA levels of sterol regulatory element binding protein 2 (SREBP2) and having sepsis or a septic shock, as recited in claim 15. The instant claims are further directed to the mental step of appreciating the natural correlation to compare between protein or mRNA levels of SREBP2 in two samples, a test sample and a control sample. As such, the instant claims recite judicial exceptions (JEs) in the form of a law of nature and abstract idea (Step 2A, Prong One: YES).
The crux of the claimed method is the appreciation of the natural correlation between protein or mRNA levels of SREBP2 in a sample and having sepsis or a septic shock. These steps of comparing can be performed by a human using mental steps or basic critical thinking, which are types of activities that have been found by the courts to represent abstract ideas (e.g., the mental comparison in Ambry Genetics, or the diagnosing an abnormal condition by performing clinical tests and thinking about the results in Grams). Obtaining and detecting by measuring the natural correlation in a biological sample would constitute insignificant extra-solution activities.
It is noted that the claims further require “diagnosing” and “treating…by administering a standard therapy. These not a particular treatment or prophylaxis, but, rather, a generic instruction to treat based upon appreciation of the natural correlation between protein or mRNA levels of SREBP2 in a sample and having sepsis or a septic shock. Hence, claim 15 does not recite additional elements that integrate the judicial exception (abstract idea) into a practical application. Integration into a practical application requires an additional element(s) or combination of additional elements in the claim to apply, rely on, or use the judicial exception in a manner that imposes meaningful limit on the judicial exception, such that the claim is more than a drafting effort designed to monopolize the exception (See for example, Slide 18 of 2019 PEG training at http://ptoweb.uspto.gov/patents/exTrain/101.html). Further, the step of “comparing” in claim 15 is performed separately from the steps of “measuring”, “diagnosing” and “treating”. There is no improvement in the functioning of a computer, or an improvement to other technology or technical field, as discussed in MPEP §§ 2106.04(d)(1) and 2106.05(a). Amended claim 15 as a whole is not limited to a particular treatment or prophylaxis because the recitation of “a standard therapy” constitutes a generic instruction to treat. Further, generally linking of the use of the judicial exception to a particular technological environment or field of use is not indicative of integration into a practical application – see MPEP 2106.05(h)”.
As such, the instant claims do not recite additional elements that integrate the JEs into a practical application (Step 2A, Prone Two: NO).
It was well-understood, routine, and conventional (WURC) at the time of filing to measure levels of protein or mRNA of SREBP2. As such, beyond the JEs, the instant claims only recite WURC data-gathering steps and generic instructions to apply the JE. These constitute insignificant extra-solution activities, which do not reasonably provide an inventive concept.
As such, the instant claims do not recite significantly more than the JE (Step 2B: NO).
Accordingly, the instant claims do not constitute patent eligible subject matter under 35 U.S.C § 101.
Response to Arguments
Applicant's arguments filed on 03/30/2026 have been fully considered but they are not persuasive.
Applicant contends on page 11 of the Remarks submitted on 03/30/2026:
“The sequence listing has been updated in accordance with Genebank No. NP_004590.2, and submitted herewith. Standard treatment protocols for sepsis or septic shock, such as administration of antibiotics, fluid resuscitation, and use of vasopressors, are well established. In light of the entire disclosure and Examples, the treatment step falls within a scope that a person skilled in the art can readily understand and implement without undue burden.”
In response:
The updated sequence constitutes new matter as explained above in detail. With respect to the treatment protocols for sepsis or septic shock, as explained above undue experimentation would be required to practice the claimed invention commensurate with the scope of the claims. The three examples provided (pages 25-28) demonstrate the following: 1) SREBP2 is activated in PBMCs of patients with SARS-CoV-2 infection; 2) expression levels of SREBP2 are correlated with hyperinflammation in lung tissues of patients with SARS-CoV-2 infection; and 3) expression of the C-terminal of the human SREBP2 is correlated with vascular development in culture cells. No working examples are provided that suggest or imply diagnosing specifically sepsis or a septic shock as a complication of an infectious disease and/or treating sepsis or a septic shock by administering a standard therapy.
Applicant contends on page 12 of the Remarks submitted on 03/30/2026:
“claim 15 has been amended to further specify the disease type to "sepsis or septic shock" as well as further clarifying the subject matter. A core technical feature of the present invention is that the expression level of SREBP2 increases with disease severity. Accordingly, the treatment step has been amended to specify that different treatments are administered depending on whether the diagnostic result indicates sepsis or septic shock. There is a close correlation between the diagnostic and treatment steps, and that the invention is characterized by determining an appropriate standard treatment based on the patient's diagnostic result.”
In response:
The instant rejection is in view of instant claim language. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). The instant claims do not mention nor require any limitation in regards to disease severity and/or selection of an appropriate treatment. As indicated above, the instant claims as amended recite insignificant extra-solution activities beyond the JEs, which do not reasonably provide an inventive concept.
Conclusion
No claims are allowed.
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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARLENE V BUCKMASTER whose telephone number is (703)756-5371. The examiner can normally be reached M-F 8-5.
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/MARLENE V BUCKMASTER/Examiner, Art Unit 1672
/NICOLE KINSEY WHITE/Primary Examiner, Art Unit 1672
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